﻿FN Clarivate Analytics Web of Science
VR 1.0
PT J
AU Alambiaga-Caravaca, AM
   Domenech-Monsell, IM
   Sebastian-Morello, M
   Calatayud-Pascual, MA
   Merino, V
   Rodilla, V
   Lopez-Castellano, A
AF Alambiaga-Caravaca, Adrian M.
   Domenech-Monsell, Iris M.
   Sebastian-Morello, Maria
   Calatayud-Pascual, M. Aracely
   Merino, Virginia
   Rodilla, Vicent
   Lopez-Castellano, Alicia
TI Development, characterization, and ex vivo evaluation of an insert for
   the ocular administration of progesterone
SO INTERNATIONAL JOURNAL OF PHARMACEUTICS
LA English
DT Article
DE Progesterone; Ocular insert; Oxidative stress; Retinitis pigmentosa; Ex
   vivo diffusion studies; Trans-corneal and trans-scleral drug delivery;
   HET-CAM assay
ID SUSTAINED DELIVERY; CONTROLLED-RELEASE; SKIN PERMEATION; MOUSE MODEL;
   DESIGN; NEUROPROTECTION; FORMULATION; SYSTEMS
AB Progesterone (PG) affords neuroprotection in degenerative diseases associated to oxidative stress, such as cataracts, age-related macular degeneration, glaucoma, diabetic retinopathy and retinitis pigmentosa. The aim of this project was to develop ocular inserts for delivery of PG to the eye. Different inserts with PG in its composition were formulated and the insert with the best characteristics (59% polyvinyl alcohol, 39% polyvinylpyrrolidone K30 and 2% propylene glycol) was selected for ex vivo studies. Physical characteristics and drug release patterns of the insert were analysed. In vitro diffusion studies revealed a controlled diffusion of progesterone. Ex vivo experiments demonstrated similar trans-corneal and trans-scleral PG diffusion (corneal apparent permeability coefficient 6.46 +/- 0.38 x 10(-7) cm/s and scleral apparent permeability coefficient 5.87 +/- 1.18 x 10(- 7) cm/s; mean +/- SD; n = 5). However, the amount of PG accumulated in scleras was statistically higher than in corneas (30.07 +/- 9.09 mu g/cm(2) and 15.56 +/- 4.36 mu g/cm(2) respectively). The PG-loaded inserts (55.6 mu g/cm(2)) were thin, translucent, showed no irritancy (HET-CAM test) and were elastic and robust, all suitable properties for its potential use in the treatment of several ocular diseases.
C1 [Alambiaga-Caravaca, Adrian M.; Domenech-Monsell, Iris M.; Sebastian-Morello, Maria; Calatayud-Pascual, M. Aracely; Rodilla, Vicent; Lopez-Castellano, Alicia] CEU Univ, Cardenal Herrera CEU Univ, Inst Biomed Sci, Dept Pharm,Fac Hlth Sci, C Santiago Ramon & Cajal,S-N, Valencia 46115, Spain.
   [Merino, Virginia] Univ Valencia, Polytech Univ Valencia, Inst Mol Recognit & Technol Dev, Dept Pharm & Pharmaceut Technol & Parasitol,Fac P, Valencia, Spain.
C3 Universidad CEU Cardenal Herrera; Universitat Politecnica de Valencia;
   University of Valencia
RP Rodilla, V; Lopez-Castellano, A (通讯作者)，CEU Univ, Cardenal Herrera CEU Univ, Inst Biomed Sci, Dept Pharm,Fac Hlth Sci, C Santiago Ramon & Cajal,S-N, Valencia 46115, Spain.
EM vrodilla@uchceu.es; alopez@uchceu.es
RI Sebastian-Morello, Maria/AAD-6812-2022; Merino, Virginia/D-1914-2010;
   Lopez Castellano, Alicia/F-9549-2016
OI Merino, Virginia/0000-0003-2220-4664; Alambiaga-Caravaca, Adrian
   Miguel/0000-0002-9642-1998; Lopez Castellano, Alicia/0000-0003-0601-1440
FU University CEU Cardenal Herrera, (Valencia, Spain); Ayudas a la
   formacion de Jovenes Investigadores CEU-SANTANDER 20/21
FX Adrian Alambiaga-Caravaca has been the beneficiary of a predoc-toral
   scholarship from "Ayudas a la formacion de Jovenes Investigadores
   CEU-SANTANDER 20/21". This work was financially supported by University
   CEU Cardenal Herrera, (Valencia, Spain) .
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NR 47
TC 1
Z9 1
U1 1
U2 4
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0378-5173
EI 1873-3476
J9 INT J PHARMACEUT
JI Int. J. Pharm.
PD SEP 5
PY 2021
VL 606
AR 120921
DI 10.1016/j.ijpharm.2021.120921
EA JUL 2021
PG 10
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA UL7LJ
UT WOS:000692828100001
PM 34303817
DA 2022-11-30
ER

PT J
AU Korhonen, E
   Hytti, M
   Piippo, N
   Kaarniranta, K
   Kauppinen, A
AF Korhonen, Eveliina
   Hytti, Maria
   Piippo, Niina
   Kaarniranta, Kai
   Kauppinen, Anu
TI Antimycin A-induced mitochondrial dysfunction regulates inflammasome
   signaling in human retinal pigment epithelial cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Retinal pigment epithelium; AIM2;
   NLRP3; Inflammasome; Interleukin-1beta; Mitochondrial damage
ID NLRP3 INFLAMMASOME; MACULAR DEGENERATION; OXIDATIVE STRESS; AIM2
   INFLAMMASOME; NALP3 INFLAMMASOME; K+ EFFLUX; ACTIVATION; DNA; TOXINS;
   DAMAGE
AB Age-related macular degeneration (AMD) is a severe retinal eye disease where dysfunctional mitochondria and damaged mitochondrial DNA in retinal pigment epithelium (RPE) have been demonstrated to underlie the pathogenesis of this devastating disease. In the present study, we aimed to examine whether damaged mitochondria induce inflammasome activation in human RPE cells. Therefore, ARPE-19 cells were primed with IL-1 alpha and exposed to the mitochondrial electron transport chain complex III inhibitor, antimycin A. We found that antimycin A-induced mitochondrial dysfunction caused caspase-1-dependent inflammasome activation and subsequent production of mature IL-1 beta and IL-18 in human RPE cells. AIM2 and NLRP3 appeared to be the responsible inflammasome receptors upon antimycin A-induced mitochondrial damage. We aimed at verifying our findings using hESC-RPE cells but antimycin A was absorbed by melanin. Therefore, results were repeated on D407 RPE cell cultures. Antimycin A-induced mitochondrial and NADPH oxidase-dependent ROS production occurred upstream of inflammasome activation, whereas K+ efflux was not required for inflammasome activation in antimycin A-treated human RPE cells. Collectively, our data emphasize that dysfunctional mitochondria regulate the assembly of inflammasome multiprotein complexes in the human RPE cells. The present study associates AIM2 with the pathogenesis of AMD.
C1 [Korhonen, Eveliina; Hytti, Maria; Piippo, Niina; Kauppinen, Anu] Univ Eastern Finland, Fac Hlth Sci, Sch Pharm, Immunoophthalmol, POB 1627, FI-70211 Kuopio, Finland.
   [Korhonen, Eveliina] Univ Helsinki, Dept Clin Chem, POB 720, FI-00029 Helsinki, Finland.
   [Korhonen, Eveliina] Helsinki Univ Hosp, POB 720, FI-00029 Helsinki, Finland.
   [Kaarniranta, Kai] Univ Eastern Finland, Inst Clin Med, Dept Ophthalmol, POB 1627, FI-70211 Kuopio, Finland.
   [Kaarniranta, Kai] Kuopio Univ Hosp, Dept Ophthalmol, POB 100, FI-70029 Kuopio, Finland.
C3 University of Eastern Finland; University of Helsinki; University of
   Helsinki; Helsinki University Central Hospital; University of Eastern
   Finland; Kuopio University Hospital; University of Eastern Finland
RP Korhonen, E; Kauppinen, A (通讯作者)，Univ Eastern Finland, Fac Hlth Sci, Sch Pharm, Immunoophthalmol, POB 1627, FI-70211 Kuopio, Finland.
EM eveliina.korhonen@uef.fi; anu.kauppinen@uef.fi
OI Korhonen, Eveliina/0000-0002-5360-7258
FU Mary and Georg C. Ehrnrooth Foundation; Paulo Foundation; Academy of
   Finland (Health Research Council) [AK297267, AK307341, AK328443];
   Padivikki and Sakari Sohlberg Foundation; Finnish Cultural Foundation -
   North Savo Regional Fund; Emil Aaltonen Foundation
FX The authors wish to thank Prof. Heli Skottman for providing hESC-RPE
   cells, and PhD Laura Hellinen for the preparation and generous gift of
   the melanin microparticles. Dr. Ewen MacDonald is warmly acknowledged
   for language revision and Res. Dir. Emeritus Antero Salminen for
   valuable discussions and critical review of the manuscript. This study
   was financially supported by the Mary and Georg C. Ehrnrooth Foundation,
   the Paulo Foundation, the Academy of Finland (Health Research Council
   projects AK297267, AK307341, AK328443) , the Padivikki and Sakari
   Sohlberg Foundation, the Finnish Cultural Foundation - North Savo
   Regional Fund, and the Emil Aaltonen Foundation.
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NR 70
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 AUG
PY 2021
VL 209
AR 108687
DI 10.1016/j.exer.2021.108687
EA JUL 2021
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA WJ8QU
UT WOS:000709303900002
PM 34216617
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Moult, EM
   Shi, YY
   Zhang, QQ
   Wang, L
   Mazumder, R
   Chen, SY
   Chu, ZD
   Feuer, W
   Waheed, NK
   Gregori, G
   Wang, RK
   Rosenfeld, PJ
   Fujimoto, JG
AF Moult, Eric M.
   Shi, Yingying
   Zhang, Qinqin
   Wang, Liang
   Mazumder, Rahul
   Chen, Siyu
   Chu, Zhongdi
   Feuer, William
   Waheed, Nadia K.
   Gregori, Giovanni
   Wang, Ruikang K.
   Rosenfeld, Philip J.
   Fujimoto, James G.
TI Analysis of correlations between local geographic atrophy growth rates
   and local OCT angiography-measured choriocapillaris flow deficits
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; AMPLITUDE-DECORRELATION ANGIOGRAPHY; FALSE
   DISCOVERY RATE; MACULAR DEGENERATION; HUMAN RETINA; QUANTIFICATION;
   PROGRESSION; DEFINITION; PERFUSION; STRATEGY
AB The purpose of this study is to quantitatively assess correlations between local geographic atrophy (GA) growth rates and local optical coherence tomography angiography (OCTA)-measured choriocapillaris (CC) flow deficits. Thirty-eight eyes from 27 patients with GA secondary to age-related macular degeneration (AMD) were imaged with a commercial 1050 nm swept-source OCTA instrument at 3 visits, each separated by similar to 6 months. Pearson correlations were computed between local GA growth rates, estimated using a biophysical GA growth model, and local OCTA CC flow deficit percentages measured along the GA margins of the baseline visits. The p-values associated with the null hypothesis of no Pearson correlation were estimated using a Monte Carlo permutation scheme that incorporates the effects of spatial autocorrelation. The null hypothesis (Pearson's rho = 0) was rejected at a Benjamini-Hochberg false discovery rate of 0.2 in 15 of the 114 visit pairs, 11 of which exhibited positive correlations; even amongst these 11 visit pairs, correlations were modest (r in [0.30, 0.53]). The presented framework appears well suited to evaluating other potential imaging biomarkers of local GA growth rates. (c) 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
C1 [Moult, Eric M.; Chen, Siyu; Fujimoto, James G.] MIT, Dept Elect Engn & Comp Sci, Res Lab Elect, Cambridge, MA 02139 USA.
   [Moult, Eric M.] Harvard & MIT, Hlth Sci & Technol, Cambridge, MA 02139 USA.
   [Shi, Yingying; Wang, Liang; Feuer, William; Gregori, Giovanni; Rosenfeld, Philip J.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USA.
   [Zhang, Qinqin; Chu, Zhongdi; Wang, Ruikang K.] Univ Washington, Dept Bioengn, Seattle, WA 98104 USA.
   [Mazumder, Rahul] MIT, Sloan Sch Management, Operat Res Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Mazumder, Rahul] MIT, Ctr Stat, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Waheed, Nadia K.] Tufts Med Ctr, New England Eye Ctr, Boston, MA 02111 USA.
C3 Massachusetts Institute of Technology (MIT); Harvard University; Bascom
   Palmer Eye Institute; University of Miami; University of Washington;
   University of Washington Seattle; Massachusetts Institute of Technology
   (MIT); Massachusetts Institute of Technology (MIT); Tufts Medical Center
RP Fujimoto, JG (通讯作者)，MIT, Dept Elect Engn & Comp Sci, Res Lab Elect, Cambridge, MA 02139 USA.
EM jgfuji@mit.edu
RI CHEN, SI/GZL-4800-2022; Wang, Ruikang/L-3889-2019
OI Wang, Ruikang/0000-0001-5169-8822
FU Macula Vision Research Foundation; Greenberg Medical Research Institute;
   Champalimaud Vision Award; Carl Zeiss Meditec Inc; BeckmanArgyros Award
   in Vision Research; Retina Research Foundation; Research to Prevent
   Blindness; Massachusetts Lions Eye Research Fund; National Institutes of
   Health [R01EY01128935, R01EY02875304]
FX Macula Vision Research Foundation; Greenberg Medical Research Institute;
   Champalimaud Vision Award; Carl Zeiss Meditec Inc; BeckmanArgyros Award
   in Vision Research; Retina Research Foundation; Research to Prevent
   Blindness; Massachusetts Lions Eye Research Fund; National Institutes of
   Health (R01EY01128935, R01EY02875304) .
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NR 59
TC 3
Z9 3
U1 0
U2 1
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 2156-7085
J9 BIOMED OPT EXPRESS
JI Biomed. Opt. Express
PD JUL 1
PY 2021
VL 12
IS 7
BP 4573
EP 4595
DI 10.1364/BOE.427819
PG 23
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 TC9OB
UT WOS:000668965600003
PM 34457433
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Tuncer, SA
   Cinar, A
   Firat, M
AF Tuncer, Seda Arslan
   Cinar, Ahmet
   Firat, Murat
TI Hybrid CNN Based Computer-Aided Diagnosis System for Choroidal
   Neovascularization, Diabetic Macular Edema, Drusen Disease Detection
   from OCT Images
SO TRAITEMENT DU SIGNAL
LA English
DT Article
DE choroidal neovascularization; drusen; diabetic macular edema; CNN-SVM
ID DEGENERATION; CLASSIFICATION
AB In the treatment of eye diseases, optical coherence tomography (OCT) is a medical imaging method that displays biological tissue layers by taking high resolution tomographic sections at the micron level. It has an important role in the diagnosis and follow-up of many diseases such as Choroidal Neovascularization (CNV), Diabetic Macular Edema (DME), age-related macular degeneration (AMD), Diabetic Retinopathy, Central Serous Retinopathy, Epiretinal Membrane, and Macular Hole. Computer-Aided Diagnostic (CAD) tools are needed in early detection and treatment monitoring of such eye diseases. In this paper, a hybrid Convolutional Neural Networks-based CAD system, which can classify Diabetic Macular Edema (DME), Drusen Choroidal Neovascularization (CNV), and normal OCT images, is proposed. The proposed system is CNN-SVM (Convolutional Neural Networks - Support Vector Machine) model and doesn't require any additional extraction of feature or noise filtering on OCT images. A total of 968 OCT images is classified in pre-trained CNN methods with Alexnet, Resnetl8 and Googlenet. Accuracy is achieved with highest Googlenet 97.4%. To examine the performance of the proposed CAD system, the CNNSVM method achieves 98.96% with the highest accuracy hybrid Alexnet-SVM model, which is implemented with Alexnet-SVM, Resnet18-SVM and Googlenet-SVM models.
C1 [Tuncer, Seda Arslan] Firat Univ, Fac Engn, Software Engn, TR-23119 Elazig, Turkey.
   [Cinar, Ahmet] Firat Univ, Fac Engn, Comp Engn, TR-23119 Elazig, Turkey.
   [Firat, Murat] Elbistan State Hosp, Dept Ophthalmol, TR-46300 Kahramanmaras, Elbistan, Turkey.
C3 Firat University; Firat University; Kahramanmaras Elbistan State
   Hospital
RP Tuncer, SA (通讯作者)，Firat Univ, Fac Engn, Software Engn, TR-23119 Elazig, Turkey.
EM satuncer@firat.edu.tr
OI arslan tuncer, seda/0000-0001-6472-8306; Firat,
   Murat/0000-0001-6040-9332
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NR 22
TC 2
Z9 2
U1 1
U2 5
PU INT INFORMATION & ENGINEERING TECHNOLOGY ASSOC
PI EDMONTON
PA #2020, SCOTIA PLACE TOWER ONE, 10060 JASPER AVE, EDMONTON, AB T5J 3R8,
   CANADA
SN 0765-0019
EI 1958-5608
J9 TRAIT SIGNAL
JI Trait. Signal
PD JUN
PY 2021
VL 38
IS 3
BP 673
EP 679
DI 10.18280/ts.380314
PG 7
WC Computer Science, Artificial Intelligence; Engineering, Electrical &
   Electronic
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Engineering
GA TV5KL
UT WOS:000681761900014
OA Bronze
DA 2022-11-30
ER

PT J
AU Waugh, DT
AF Waugh, Declan Timothy
TI The Contribution of Fluoride to the Pathogenesis of Eye Diseases:
   Molecular Mechanisms and Implications for Public Health
SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
LA English
DT Review
DE fluoride; age-related macular degeneration; cataract; glaucoma;
   molecular mechanisms; heat shock proteins; FoxO proteins; BCL-2; Na; K
   plus -ATPase; NF-kB; Nrf2; IL-6; diabetes; down syndrome; schizophrenia
ID NF-KAPPA-B; HEAT-SHOCK PROTEINS; AGE-RELATED MACULOPATHY;
   HEAT-SHOCK-PROTEIN-70 GENE POLYMORPHISMS; ATTENUATES DIABETES
   DEVELOPMENT; LIPID-PEROXIDATION LEVELS; RETINAL GANGLION-CELLS;
   GLYCATION END-PRODUCTS; NA+-K+-ATPASE; OXIDATIVE STRESS
AB This study provides diverse lines of evidence demonstrating that fluoride (F) exposure contributes to degenerative eye diseases by stimulating or inhibiting biological pathways associated with the pathogenesis of cataract, age-related macular degeneration and glaucoma. As elucidated in this study, F exerts this effect by inhibiting enolase, -crystallin, Hsp40, Na+, K+-ATPase, Nrf2, -GCS, HO-1 Bcl-2, FoxO1, SOD, PON-1 and glutathione activity, and upregulating NF-B, IL-6, AGEs, HsP27 and Hsp70 expression. Moreover, F exposure leads to enhanced oxidative stress and impaired antioxidant activity. Based on the evidence presented in this study, it can be concluded that F exposure may be added to the list of identifiable risk factors associated with pathogenesis of degenerative eye diseases. The broader impact of these findings suggests that reducing F intake may lead to an overall reduction in the modifiable risk factors associated with degenerative eye diseases. Further studies are required to examine this association and determine differences in prevalence rates amongst fluoridated and non-fluoridated communities, taking into consideration other dietary sources of F such as tea. Finally, the findings of this study elucidate molecular pathways associated with F exposure that may suggest a possible association between F exposure and other inflammatory diseases. Further studies are also warranted to examine these associations.
C1 [Waugh, Declan Timothy] EnviroManagement Serv, 11 Riverview,Dohertys Rd, Bandon P72 YF10, Cork, Ireland.
RP Waugh, DT (通讯作者)，EnviroManagement Serv, 11 Riverview,Dohertys Rd, Bandon P72 YF10, Cork, Ireland.
EM declan@enviro.ie
RI Waugh, Declan/AAW-8222-2020
OI Waugh, Declan/0000-0003-1941-9656
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NR 336
TC 7
Z9 7
U1 1
U2 5
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 1661-7827
EI 1660-4601
J9 INT J ENV RES PUB HE
JI Int. J. Environ. Res. Public Health
PD MAR 1
PY 2019
VL 16
IS 5
AR 856
DI 10.3390/ijerph16050856
PG 28
WC Environmental Sciences; Public, Environmental & Occupational Health
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health
GA HQ8HD
UT WOS:000462664200181
PM 30857240
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Nakamura, M
   Yako, T
   Kuse, Y
   Inoue, Y
   Nishinaka, A
   Nakamura, S
   Shimazawa, M
   Hara, H
AF Nakamura, Maho
   Yako, Tomohiro
   Kuse, Yoshiki
   Inoue, Yuki
   Nishinaka, Ann
   Nakamura, Shinsuke
   Shimazawa, Masamitsu
   Hara, Hideaki
TI Exposure to excessive blue LED light damages retinal pigment epithelium
   and photoreceptors of pigmented mice
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
ID AGE-RELATED MACULOPATHY; GROWTH-FACTOR; LIPOFUSCIN ACCUMULATION; MACULAR
   DEGENERATION; MOUSE MODEL; RAT RETINA; CELLS; INVOLVEMENT; MELANIN; A2E
AB To determine the characteristics of the damages of the retinal pigment epithelium (RPE) and photoreceptors of pigmented mice induced by exposure to blue light emitting diode (LED) light, and to determine the mechanisms causing the damages. Exposure to blue LED light for 3 days induced retinal damage, and the characteristics of the damage differed from that induced by white fluorescent light exposure. Ophthalmoscopy showed that blue LED exposure for 3 days induced white spots on the retina, and histological examinations showed materials accumulated at the IS/OS junction of the photoreceptors. The accumulated materials were stained by ionized calcium binding adapter molecule-1 (Iba-1), a marker for macrophages. The debris was also positive for periodic acid-Schiff (PAS). An enlarging the area of RPE was detected just after the blue LED exposure especially around the optic nerve, and this led to a secondary degeneration of the photoreceptors. Exposure of pigmented mice to 3 consecutive days of blue LED light will cause RPE and photoreceptor damage. The damage led to an accumulation of macrophages and drusen-like materials around the outer segments of the photoreceptors. This blue light exposed model may be useful for investigating the pathogenesis of nonexudative age-related macular degeneration.
C1 [Nakamura, Maho; Yako, Tomohiro; Kuse, Yoshiki; Inoue, Yuki; Nishinaka, Ann; Nakamura, Shinsuke; Shimazawa, Masamitsu; Hara, Hideaki] Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan.
C3 Gifu Pharmaceutical University
RP Shimazawa, M; Hara, H (通讯作者)，Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan.
EM shimazawa@gifu-pu.ac.jp; hidehara@gifu-pu.ac.jp
RI Kuse, Yoshiki/AAB-7445-2021
OI Hara, Hideaki/0000-0003-2046-9001
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NR 69
TC 31
Z9 32
U1 4
U2 34
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD DEC
PY 2018
VL 177
BP 1
EP 11
DI 10.1016/j.exer.2018.07.022
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HE7OO
UT WOS:000453628000001
PM 30040948
DA 2022-11-30
ER

PT J
AU Xu, QY
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   Rajapakse, S
   Matsubara, JA
AF Xu, Qinyuan
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TI Understanding AMD by analogy: systematic review of lipid-related common
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SO LIPIDS IN HEALTH AND DISEASE
LA English
DT Review
DE Lipids/oxidation; Cholesterol; Apolipoproteins; Inflammation;
   Complement; Macrophages; Diseases
ID COMPLEMENT FACTOR-H; MIGRATION INHIBITORY FACTOR; COLONY-STIMULATING
   FACTOR; LOW-DENSITY LIPOPROTEINS; AGE-RELATED MACULOPATHY; MACULAR
   DEGENERATION; ALZHEIMERS-DISEASE; MEMBRANOPROLIFERATIVE
   GLOMERULONEPHRITIS; AMYLOID-BETA; APOLIPOPROTEIN-E
AB Rationale: Age-related macular degeneration (AMD) is one of the leading causes of blindness among the elderly. Due to its complex etiology, current treatments have been insufficient. Previous studies reveal three systems closely involved in AMD pathogenesis: lipid metabolism, oxidation and inflammation. These systems are also involved in Alzheimer's disease, atherosclerosis and glomerulonephritis. Understanding commonalities of these four diseases may provide insight into AMD etiology.
   Objectives: To understand AMD pathogenesis by analogy and suggest ideas for future research, this study summarizes main commonalities in disease pathogenesis of AMD, Alzheimer's disease, atherosclerosis and glomerulonephritis.
   Methods: Articles were identified through PubMed, Ovid Medline and Google Scholar. We summarized the common findings and synthesized critical differences.
   Results: Oxidation, lipid deposition, complement activation, and macrophage recruitment are involved in all four diseases shown by genetic, molecular, animal and human studies. Shared genetic variations further strengthen their connection. Potential areas for future research are suggested throughout the review.
   Conclusions: The four diseases share many steps of an overall framework of pathogenesis. Various oxidative sources cause oxidative stress. Oxidized lipids and related molecules accumulate and lead to complement activation, macrophage recruitment and pathology. Investigations that arise under this structure may aid us to better understand AMD pathology.
C1 [Xu, Qinyuan; Cao, Sijia; Rajapakse, Sanjeeva; Matsubara, Joanne A.] Univ British Columbia, Fac Med, Dept Ophthalmol & Visual Sci, Vancouver, BC V5Z 3N9, Canada.
C3 University of British Columbia
RP Matsubara, JA (通讯作者)，Univ British Columbia, Fac Med, Dept Ophthalmol & Visual Sci, Vancouver, BC V5Z 3N9, Canada.
EM jms@mail.ubc.ca
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NR 129
TC 31
Z9 33
U1 3
U2 19
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1476-511X
J9 LIPIDS HEALTH DIS
JI Lipids Health Dis.
PD JAN 4
PY 2018
VL 17
AR 3
DI 10.1186/s12944-017-0647-7
PG 13
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA FS0UW
UT WOS:000419490200002
PM 29301530
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Malek, G
   Busik, J
   Grant, MB
   Choudhary, M
AF Malek, Goldis
   Busik, Julia
   Grant, Maria B.
   Choudhary, Mayur
TI Models of retinal diseases and their applicability in drug discovery
SO EXPERT OPINION ON DRUG DISCOVERY
LA English
DT Review
DE Age-related macular degeneration; animal models; cell culture models;
   diabetic retinopathy
ID COMPLEMENT FACTOR-H; ENDOTHELIAL GROWTH-FACTOR; AGE-RELATED MACULOPATHY;
   EXPERIMENTAL DIABETIC-RETINOPATHY; PIGMENT EPITHELIAL-CELLS;
   HIGH-GLUCOSE CONDITIONS; GLYCATION END-PRODUCTS; NITRIC-OXIDE SYNTHASE;
   MANGANESE SUPEROXIDE-DISMUTASE; DEGENERATION-LIKE PATHOLOGY
AB Introduction: The impact of vision debilitating diseases is a global public health concern, which will continue until effective preventative and management protocols are developed. Two retinal diseases responsible for the majority of vision loss in the working age adults and elderly populations are diabetic retinopathy (DR) and age-related macular degeneration (AMD), respectively. Model systems, which recapitulate aspects of human pathology, are valid experimental modalities that have contributed to the identification of signaling pathways involved in disease development and consequently potential therapies.
   Areas covered: The pathology of DR and AMD, which serve as the basis for designing appropriate models of disease, is discussed. The authors also review in vitro and in vivo models of DR and AMD and evaluate the utility of these models in exploratory and pre-clinical studies.
   Expert opinion: The complex nature of non-Mendelian diseases such as DR and AMD has made identification of effective therapeutic treatments challenging. However, the authors believe that while in vivo models are often criticized for not being a 'perfect' recapitulation of disease, they have been valuable experimentally when used with consideration of the strengths and limitations of the experimental model selected and have a place in the drug discovery process.
C1 [Malek, Goldis; Choudhary, Mayur] Duke Univ, Sch Med, Dept Ophthalmol, Durham, NC USA.
   [Malek, Goldis] Duke Univ, Sch Med, Dept Pathol, Durham, NC 27706 USA.
   [Busik, Julia] Michigan State Univ, Dept Physiol, E Lansing, MI 48824 USA.
   [Grant, Maria B.] Univ Alabama Birmingham, Dept Ophthalmol, Birmingham, AL USA.
C3 Duke University; Duke University; Michigan State University; University
   of Alabama System; University of Alabama Birmingham
RP Malek, G (通讯作者)，Duke Univ, 2351 Erwin Rd,POB 3802, Durham, NC 27710 USA.
EM gmalek@duke.edu
RI Busik, Julia V/A-2698-2010; Choudhary, Mayur/AAU-3497-2021
OI Busik, Julia V/0000-0003-3453-7124; Choudhary,
   Mayur/0000-0001-8056-011X; Malek, Goldis/0000-0003-0026-2388
FU National Eye Institute [EY025383, EY02868, EY016077, P30 EY005722];
   Research to Prevent Blindness, Inc (RPB); Edward N. & Della L. Thome
   Memorial Foundation; BrightFocus Macular Degeneration Grant; NATIONAL
   EYE INSTITUTE [R01EY016077, R01EY020868, P30EY005722, R01EY025383]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DIABETES AND
   DIGESTIVE AND KIDNEY DISEASES [P30DK020572] Funding Source: NIH RePORTER
FX The authors acknowledge the following funding agencies for their support
   of our ongoing research projects: the National Eye Institute grants:
   EY02868 (to G Malek), EY016077 (to JV Busik), EY025383 (to MB Grant and
   JV Busik), and P30 EY005722 (to the Duke Eye Center); the Edward N. &
   Della L. Thome Memorial Foundation Award (to G Malek); BrightFocus
   Macular Degeneration Grant (to G Malek) and the Research to Prevent
   Blindness, Inc (RPB) Core grant (to the Duke Eye Center).
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NR 261
TC 22
Z9 22
U1 0
U2 12
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.
PY 2018
VL 13
IS 4
BP 359
EP 377
DI 10.1080/17460441.2018.1430136
PG 19
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA FY7PZ
UT WOS:000427056500008
PM 29382242
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Minasyan, L
   Sreekumar, PG
   Hinton, DR
   Kannan, R
AF Minasyan, Leonid
   Sreekumar, Parameswaran G.
   Hinton, David R.
   Kannan, Ram
TI Protective Mechanisms of the Mitochondrial-Derived Peptide Humanin in
   Oxidative and Endoplasmic Reticulum Stress in RPE Cells
SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
LA English
DT Review
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION AMD;
   ALZHEIMERS-DISEASE; DNA DAMAGE; SKELETAL-MUSCLES; FREE-RADICALS; ER;
   APOPTOSIS; DEATH; TARGET
AB Age-related macular degeneration (AMD) is the leading cause of severe and irreversible vision loss and is characterized by progressive degeneration of the retina resulting in loss of central vision. The retinal pigment epithelium (RPE) is a critical site of pathology of AMD. Mitochondria and the endoplasmic reticulum which lie in close anatomic proximity to each other are targets of oxidative stress and endoplasmic reticulum (ER) stress, respectively, and contribute to the progression of AMD. The two organelles exhibit close interactive function via various signaling mechanisms. Evidence for ER-mitochondrial crosstalk in RPE under ER stress and signaling pathways of apoptotic cell death is presented. The role of humanin (HN), a prominent member of a newly discovered family of mitochondrial-derived peptides (MDPs) expressed from an open reading frame of mitochondrial 16S rRNA, in modulation of ER and oxidative stress in RPE is discussed. HN protected RPE cells from oxidative and ER stress-induced cell death by upregulation of mitochondrial GSH, inhibition of ROS generation, and caspase 3 and 4 activation. The underlying mechanisms of ER-mitochondrial crosstalk and modulation by exogenous HN are discussed. The therapeutic use of HN and related MDPs could potentially prove to be a valuable approach for treatment of AMD.
C1 [Minasyan, Leonid; Hinton, David R.] Univ Southern Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA USA.
   [Sreekumar, Parameswaran G.; Kannan, Ram] Doheny Eye Inst, Arnold & Mabel Beckman Macular Res Ctr, 1355 San Pablo St, Los Angeles, CA 90033 USA.
   [Hinton, David R.] Univ Southern Calif, USC Roski Eye Inst, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA USA.
C3 University of Southern California; Doheny Eye Institute; University of
   Southern California
RP Kannan, R (通讯作者)，Doheny Eye Inst, Arnold & Mabel Beckman Macular Res Ctr, 1355 San Pablo St, Los Angeles, CA 90033 USA.
EM rkannan@doheny.org
RI kannan, ram/ABB-7154-2020
OI kannan, ram/0000-0002-1583-3414; /0000-0002-9425-3986
FU Core Grant [EY03040]; Arnold and Mabel Beckman Foundation;  [EY01545]
FX The authors thank Ernesto Barron and Eric Barron for the help with
   figures and Jan Lee for secretarial assistance. Work from their
   laboratory was supported by Grant EY01545 (David R. Hinton) and by Core
   Grant EY03040 and the Arnold and Mabel Beckman Foundation (David R.
   Hinton and Ram Kannan).
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NR 101
TC 40
Z9 42
U1 0
U2 9
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 2017
VL 2017
AR 1675230
DI 10.1155/2017/1675230
PG 11
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA FD1TK
UT WOS:000407319400001
PM 28814984
OA gold, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Zhang, SX
   Ma, JH
   Bhatta, M
   Fliesler, SJ
   Wang, JJ
AF Zhang, Sarah X.
   Ma, Jacey H.
   Bhatta, Maulasri
   Fliesler, Steven J.
   Wang, Joshua J.
TI The unfolded protein response in retinal vascular diseases: Implications
   and therapeutic potential beyond protein folding
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Article
DE Endoplasmic reticulum stress; Unfolded protein response; Retina;
   Angiogenesis; VEGF; Endothelial cells
ID ENDOPLASMIC-RETICULUM STRESS; ENDOTHELIAL PROGENITOR CELLS;
   THIOREDOXIN-INTERACTING PROTEIN; PIGMENT EPITHELIAL-CELLS; AMINO-ACID
   DEPRIVATION; XBP1 MESSENGER-RNA; ALPHA-B-CRYSTALLIN; ER QUALITY-CONTROL;
   GROWTH-FACTOR; BONE-MARROW
AB Angiogenesis is a complex, step-wise process of new vessel formation that is involved in both normal embryonic development as well as postnatal pathological processes, such as cancer, cardiovascular disease, and diabetes. Aberrant blood vessel growth, also known as neovascularization, in the retina and the choroid is a major cause of vision loss in severe eye diseases, such as diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, and central and branch retinal vein occlusion. Yet, retinal neovascularization is causally and dynamically associated with vasodegeneration, ischemia, and vascular remodeling in retinal tissues. Understanding the mechanisms of retinal neovascularization is an urgent unmet need for developing new treatments for these devastating diseases. Accumulating evidence suggests a vital role for the unfolded protein response (UPR) in regulation of angiogenesis, in part through coordinating the secretion of pro-angiogenic growth factors, such as VEGF, and modulating endothelial cell survival and activity. Herein, we summarize current research in the context of endoplasmic reticulum (ER) stress and UPR signaling in retinal angiogenesis and vascular remodeling, highlighting potential implications of targeting these stress response pathways in the prevention and treatment of retinal vascular diseases that result in visual deficits and blindness. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Zhang, Sarah X.; Ma, Jacey H.; Bhatta, Maulasri; Fliesler, Steven J.; Wang, Joshua J.] SUNY Buffalo, Dept Ophthalmol, Buffalo, NY 14214 USA.
   [Zhang, Sarah X.; Ma, Jacey H.; Bhatta, Maulasri; Fliesler, Steven J.; Wang, Joshua J.] SUNY Buffalo, Dept Biochem, Buffalo, NY 14214 USA.
   [Zhang, Sarah X.; Ma, Jacey H.; Bhatta, Maulasri; Fliesler, Steven J.] SUNY Eye Inst, Buffalo, NY USA.
   [Ma, Jacey H.] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China.
   [Fliesler, Steven J.] Vet Adm Western New York Healthcare Syst, Res Serv, Buffalo, NY USA.
C3 State University of New York (SUNY) System; State University of New York
   (SUNY) Buffalo; State University of New York (SUNY) System; State
   University of New York (SUNY) Buffalo; Sun Yat Sen University
RP Zhang, SX (通讯作者)，SUNY Buffalo, Dept Ophthalmol, Farber Hall 308, Buffalo, NY 14214 USA.
EM xzhang38@buffalo.edu
RI Fliesler, Steven J./AAE-9243-2020
OI Fliesler, Steven/0000-0002-2557-142X
FU NIH/NEI [EY019949, EY025061, EY007361]; Oklahoma Center for the
   Advancement of Science and Technology [HR10-060]; American Diabetes
   Association [7-11-BS-182]; Research to Prevent Blindness; NATIONAL EYE
   INSTITUTE [R01EY019949, R21EY025061, R01EY007361] Funding Source: NIH
   RePORTER
FX This work was supported, in part, by NIH/NEI grants EY019949 (SXZ),
   EY025061 (SXZ) and EY007361 (SJF), by grants from the Oklahoma Center
   for the Advancement of Science and Technology HR10-060 (SXZ) and the
   American Diabetes Association, 7-11-BS-182 (SXZ), by an Unrestricted
   Grant to the Department of Ophthalmology, SUNY-Buffalo, from Research to
   Prevent Blindness (SJF, SXZ), and by facilities and resources provided
   by the Veterans Administration Western New York Healthcare System (SJF).
   The views expressed herein do not necessarily reflect those of the
   Veterans Administration or the U.S. Government.
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NR 253
TC 52
Z9 53
U1 0
U2 19
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 2015
VL 45
BP 111
EP 131
DI 10.1016/j.preteyeres.2014.12.001
PG 21
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CD1LL
UT WOS:000350836300004
PM 25529848
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Li, MY
   Jia, C
   Kazmierkiewicz, KL
   Bowman, AS
   Tian, LF
   Liu, YC
   Gupta, NA
   Gudiseva, HV
   Yee, SS
   Kim, M
   Dentchev, T
   Kimble, JA
   Parker, JS
   Messinger, JD
   Hakonarson, H
   Curcio, CA
   Stambolian, D
AF Li, Mingyao
   Jia, Cheng
   Kazmierkiewicz, Krista L.
   Bowman, Anita S.
   Tian, Lifeng
   Liu, Yichuan
   Gupta, Neel A.
   Gudiseva, Harini V.
   Yee, Stephanie S.
   Kim, Mijin
   Dentchev, Tzvete
   Kimble, James A.
   Parker, John S.
   Messinger, Jeffrey D.
   Hakonarson, Hakon
   Curcio, Christine A.
   Stambolian, Dwight
TI Comprehensive analysis of gene expression in human retina and supporting
   tissues
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID AGE-RELATED MACULOPATHY; SUBRETINAL DRUSENOID DEPOSITS; MACULAR
   DEGENERATION; ALZHEIMERS-DISEASE; PIGMENT EPITHELIUM; GEOGRAPHIC
   ATROPHY; BRUCHS MEMBRANE; PHOTORECEPTOR TOPOGRAPHY; REFRACTIVE ERROR;
   GANGLION-CELLS
AB Understanding the influence of gene expression on the molecular mechanisms underpinning human phenotypic diversity is fundamental to being able to predict health outcomes and treat disease. We have carried out whole transcriptome expression analysis on a series of eight normal human postmortem eyes by RNA sequencing. Here we present data showing that similar to 80% of the transcriptome is expressed in the posterior layers of the eye and that there is significant differential expression not only between the layers of the posterior part of the eye but also between locations of a tissue layer. These differences in expression also extend to alternative splicing and splicing factors. Differentially expressed genes are enriched for genes associated with psychiatric, immune and cardiovascular disorders. Enrichment categories for gene ontology included ion transport, synaptic transmission and visual and sensory perception. Lastly, allele-specific expression was found to be significant for CFH, C3 and CFB, which are known risk genes for age-related macular degeneration. These expression differences should be useful in determining the underlying biology of associations with common diseases of the human retina, retinal pigment epithelium and choroid and in guiding the analysis of the genomic regions involved in the control of normal gene expression.
C1 [Li, Mingyao; Jia, Cheng; Liu, Yichuan] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
   [Kazmierkiewicz, Krista L.; Bowman, Anita S.; Gudiseva, Harini V.; Yee, Stephanie S.; Kim, Mijin; Stambolian, Dwight] Univ Penn, Perelman Sch Med, Dept Ophthalmol, Philadelphia, PA 19104 USA.
   [Dentchev, Tzvete] Univ Penn, Perelman Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA.
   [Hakonarson, Hakon] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.
   [Tian, Lifeng; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
   [Hakonarson, Hakon] Childrens Hosp Philadelphia, Div Pulm Med, Philadelphia, PA 19104 USA.
   [Gupta, Neel A.] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA.
   [Kimble, James A.] Retina Specialists Alabama, Birmingham, AL 35294 USA.
   [Kimble, James A.; Parker, John S.; Messinger, Jeffrey D.; Curcio, Christine A.] Univ Alabama Sch Med, Dept Ophthalmol, Birmingham, AL 35294 USA.
C3 University of Pennsylvania; Pennsylvania Medicine; University of
   Pennsylvania; Pennsylvania Medicine; University of Pennsylvania;
   Pennsylvania Medicine; University of Pennsylvania; Pennsylvania
   Medicine; University of Pennsylvania; Pennsylvania Medicine; Childrens
   Hospital of Philadelphia; University of Pennsylvania; Pennsylvania
   Medicine; Childrens Hospital of Philadelphia; Drexel University
RP Stambolian, D (通讯作者)，Univ Penn, Perelman Sch Med, Dept Ophthalmol, Philadelphia, PA 19104 USA.
EM stamboli@mail.med.upenn.edu; stamboli@mail.med.upenn.edu
RI Liu, Yichuan/AAF-3893-2021
OI LIU, YICHUAN/0000-0003-2023-072X; Bowman, Anita S./0000-0002-8651-5317
FU Arnold and Mabel Beckman Initiative for Macular Research
FX The Arnold and Mabel Beckman Initiative for Macular Research.
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NR 68
TC 79
Z9 79
U1 0
U2 9
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 AUG 1
PY 2014
VL 23
IS 15
BP 4001
EP 4014
DI 10.1093/hmg/ddu114
PG 14
WC Biochemistry & Molecular Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AM2GV
UT WOS:000339669200007
PM 24634144
OA hybrid, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Li, CP
   Yao, J
   Tao, ZF
   Li, XM
   Jiang, Q
   Yan, B
AF Li, Chao-Peng
   Yao, Jin
   Tao, Zhi-Fu
   Li, Xiu-Miao
   Jiang, Qin
   Yan, Biao
TI Epigallocatechin-gallate (EGCG) regulates autophagy in human retinal
   pigment epithelial cells: A potential role for reducing UVB
   light-induced retinal damage
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE EGCG; Autophagy; RPE cells; mTOR signaling
ID (-)-EPIGALLOCATECHIN GALLATE; INDUCED APOPTOSIS; OXIDATIVE STRESS;
   DISEASE; HEALTH; MECHANISMS; PATHWAYS; PROTECTS; DEATH
AB Autophagy is an intracellular catabolic process involved in protein and organelle degradation via the lysosomal pathway that has been linked in the pathogenesis of age-related macular degeneration (AMD). UVB irradiation-mediated degeneration of the macular retinal pigment epithelial (RPE) cells is an important hallmark of AMD, which is along with the change in RPE autophagy. Thus, pharmacological manipulation of RPE autophagy may offer an alternative therapeutic target in AMD. Here, we found that epigallocatechin-3-gallate (EGCG), a polyphenolic compound from green tea, plays a regulatory role in UVB irradiation-induced autophagy in RPE cells. UVB irradiation results in a marked increase in the amount of LC3-II protein in a dose-dependent manner. EGCG administration leads to a significant reduction in-the formation of LC3-II and autophagosomes. mTOR signaling activation is required for EGCG-induced LC3-II formation, as evidenced by the fact that EGCG-induced LC3-II formation is significantly impaired by rapamycin administration. Moreover, EGCG significantly alleviates the toxic effects of UVB irradiation on RPE cells in an autophagy-dependent manner. Collectively, our study reveals a novel role of EGCG in RPE autophagy. EGCG may be exploited as a potential therapeutic reagent for the treatment of pathological conditions associated with abnormal autophagy. Published by Elsevier Inc.
C1 [Li, Chao-Peng; Yao, Jin; Tao, Zhi-Fu; Li, Xiu-Miao; Jiang, Qin; Yan, Biao] Nanjing Med Univ, Hosp Eye, Nanjing 210029, Jiangsu, Peoples R China.
C3 Nanjing Medical University
RP Jiang, Q (通讯作者)，Nanjing Med Univ, Hosp Eye, 138 Han Zhong Rd, Nanjing 210029, Jiangsu, Peoples R China.
EM jqin710@vip.sina.com; yanbiao1982@hotmail.com
FU National Natural Science Foundation of China [81070744, 81271028];
   Medical Science and Technology Development Project Fund of Nanjing
   [ZKX12047, YKK12208]
FX This work was generously supported by Grants from the National Natural
   Science Foundation of China (Grant No. 81070744 to Q.J. and Grant No.
   81271028 to J.Y.), and the Medical Science and Technology Development
   Project Fund of Nanjing (Grant No. ZKX12047 to Q.J. and Grant No.
   YKK12208 to J.Y.).
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NR 33
TC 35
Z9 40
U1 0
U2 44
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD SEP 6
PY 2013
VL 438
IS 4
BP 739
EP 745
DI 10.1016/j.bbrc.2013.07.097
PG 7
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 218TG
UT WOS:000324454800028
PM 23916613
DA 2022-11-30
ER

PT J
AU Skaat, A
   Chetrit, A
   Belkin, M
   Kinori, M
   Kalter-Leibovici, O
AF Skaat, Alon
   Chetrit, Angela
   Belkin, Michael
   Kinori, Michael
   Kalter-Leibovici, Ofra
TI Time Trends in the Incidence and Causes of Blindness in Israel
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; DIABETIC-RETINOPATHY; MACULAR DEGENERATION;
   VISUAL IMPAIRMENT; INCIDENCE RATES; PREVALENCE; PHARMACOTHERAPY;
   GLAUCOMA
AB PURPOSE: To evaluate time trends in the incidence and causes of new cases of blindness in Israel between 1999 and 2008.
   DESIGN: Descriptive, retrospective population-based study.
   METHODS: During the decade of the study, 19 862 inhabitants of Israel were newly registered as legally blind. Data were retrieved from the 1999 to 2008 annual reports of the National Registry of the Blind in Israel and were reviewed retrospectively. Specific rates by age, gender, calendar year, and cause of blindness were calculated. Total and cause-specific annual age-standardized rates were calculated as well. Findings were evaluated by the use of Poisson regression models.
   RESULTS: The age-standardized rate of incidence of newly registered legal blindness at the end of the studied decade was half of that at the beginning, declining from 33.8 per 100 000 in 1999 to 16.6 per 100 000 in 2008. The decline mainly was attributable to a decreased incidence of blindness resulting from age-related macular degeneration, glaucoma, diabetic retinopathy, and cataract.
   CONCLUSIONS: Contemporary interventions in ophthalmology combined with widely available universal free access to healthcare seem to be effective in causing a major reduction in the incidence of blindness. (Am J Ophthalmol 2012;153:214-221. 2012 by Elsevier Inc. All rights reserved.)
C1 [Skaat, Alon; Kinori, Michael] Tel Aviv Univ, Goldschleger Eye Inst, Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel.
   [Chetrit, Angela; Kalter-Leibovici, Ofra] Gertner Inst Epidemiol & Hlth Policy Res, Cardiovasc Epidemiol Unit, Tel Hashomer, Israel.
   [Belkin, Michael] Tel Aviv Univ, Goldschleger Eye Res Inst, IL-52621 Tel Hashomer, Israel.
   [Kalter-Leibovici, Ofra] Tel Aviv Univ, Sackler Fac Med, Dept Epidemiol & Prevent Med, IL-69978 Tel Aviv, Israel.
C3 Chaim Sheba Medical Center; Tel Aviv University; Tel Aviv University;
   Tel Aviv University; Sackler Faculty of Medicine
RP Skaat, A (通讯作者)，Tel Aviv Univ, Goldschleger Eye Inst, Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel.
EM skaatalon@gmail.com
RI Belkin, Michael/AAK-4728-2020
OI Kinori, Michael/0000-0002-7162-8116
CR Abu Asleh S, 2007, ISRAEL MED ASSOC J, V9, P656
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NR 30
TC 79
Z9 84
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 FEB
PY 2012
VL 153
IS 2
BP 214
EP 221
DI 10.1016/j.ajo.2011.08.035
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 884OQ
UT WOS:000299717800005
PM 22264945
DA 2022-11-30
ER

PT J
AU Bartlett, H
   Eperjesi, F
AF Bartlett, Hannah
   Eperjesi, Frank
TI Apparent motion photometry: evaluation and reliability of a novel method
   for the measurement of macular pigment
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID HETEROCHROMATIC FLICKER PHOTOMETRY; OPTICAL-DENSITY; PRIMATE RETINAS;
   PROTECTIVE ROLE; OLDER SUBJECTS; EYE DISEASE; AGE; DEGENERATION;
   CAROTENOIDS; SAMPLE
AB Background/aims Macular pigment is thought to protect the macula against exposure to light and oxidative stress, both of which may play a role in the development of age-related macular degeneration. The aim was to clinically evaluate a novel cathode-ray-tube-based method for measurement of macular pigment optical density (MPOD) known as apparent motion photometry (AMP).
   Methods The authors took repeat readings of MPOD centrally (0 degrees) and at 3 degrees eccentricity for 76 healthy subjects (mean (+/- SD) 26.5 +/- 13.2 years, range 18-74 years).
   Results The overall mean MPOD for the cohort was 0.50 +/- 0.24 at 0 degrees, and 0.28 +/- 0.20 at 3 degrees eccentricity; these values were significantly different (t = -8.905, p<0.001). The coefficients of repeatability were 0.60 and 0.48 for the 0 and 3 degrees measurements respectively.
   Conclusions The data suggest that when the same operator is taking repeated 0 degrees AMP MPOD readings over time, only changes of more than 0.60 units can be classed as clinically significant. In other words, AMP is not suitable for monitoring changes in MPOD over time, as increases of this magnitude would not be expected, even in response to dietary modification or nutritional supplementation.
C1 [Bartlett, Hannah; Eperjesi, Frank] Aston Univ, Sch Life & Hlth Sci, Ophthalm Res Grp, Birmingham B4 7ET, W Midlands, England.
C3 Aston University
RP Bartlett, H (通讯作者)，Aston Univ, Sch Life & Hlth Sci, Ophthalm Res Grp, Birmingham B4 7ET, W Midlands, England.
EM h.e.bartlett@aston.ac.uk
RI Eperjesi, Frank/A-9275-2013
OI Eperjesi, Frank/0000-0003-4358-0095; Bartlett Eperjesi, Hannah
   E/0000-0002-7531-6902
FU Macular Disease Society
FX HB was funded by a grant from the Macular Disease Society.
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NR 25
TC 4
Z9 4
U1 0
U2 5
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD MAY
PY 2011
VL 95
IS 5
BP 662
EP 665
DI 10.1136/bjo.2009.178137
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 752TN
UT WOS:000289717300016
PM 20805121
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Bonilha, VL
   Rayborn, ME
   Shadrach, KG
   Li, Y
   Lundwal, A
   Malm, J
   Hollyfield, JG
AF Bonilha, Vera L.
   Rayborn, Mary E.
   Shadrach, Karen G.
   Li, Yong
   Lundwal, Ake
   Malm, Johan
   Hollyfield, Joe G.
TI Semenogelins in the human retina: Differences in distribution and
   content between AMD and normal donor tissues
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE semenogelins; zinc; immunohistochemistry; AMD; retina
ID MACULAR DEGENERATION; HUMAN-SEMEN; PREDOMINANT PROTEIN; PIGMENT
   EPITHELIUM; ZINC-DEFICIENCY; BRUCHS MEMBRANE; MAIN PROTEIN; AGE;
   EXPRESSION; DEPOSITS
AB The two cellular targets of interest in age-related macular degeneration (AMD) are the photoreceptors and the RPE. However, the mechanisms involved in AMD pathology are not yet fully understood. In the present report, we extend our previous studies on semenogelin proteins (Sgs) in normal human retina and compare these with the distribution in retinas from AMD donor eyes. Semenogelins I (SaI) and II (SaII) are the major structural protein components of semen coagulum, but have been recently found in non-genital tissues as well. Cryo and paraffin sections of human retina were processed for both immunofluorescence and DAB reaction with a specific antibody. The presence of Sal was analyzed in retina and RPE total lysates and SaI was detected by western blot in human retina and RPE. The intensity of immunoreactivity was significantly reduced in the AMD eyes. Sal is expressed in the normal human retina and in the retina of AMD donor eyes, where localization was detected in the photoreceptors and in a few ganglion cells. We find the distribution of Sal in the AMD retinas substantially lower than observed in normal retina. Sal localization to photoreceptors and the RPE suggests a possible function related to the ability of these cells to sequester zinc. (C) 2007 Elsevier Ltd. All rights reserved.
C1 [Bonilha, Vera L.; Rayborn, Mary E.; Shadrach, Karen G.; Li, Yong; Hollyfield, Joe G.] Cleveland Clin, Lerner Coll Med, Cole Eye Inst, Dept Ophthalmol, Cleveland, OH 44195 USA.
   [Lundwal, Ake; Malm, Johan] Lund Univ, Univ Hosp, Dept Lab Med, MAS, S-20502 Malmo, Sweden.
C3 Case Western Reserve University; Cleveland Clinic Foundation; Lund
   University; Skane University Hospital
RP Bonilha, VL (通讯作者)，Cleveland Clin, Lerner Coll Med, Cole Eye Inst, Dept Ophthalmol, 9500 Euclid Ave, Cleveland, OH 44195 USA.
EM bonilhav@ccf.org
RI Bonilha, Vera/AAS-8566-2020
OI Bonilha, Vera/0000-0002-6166-5124; Lundwall, Ake/0000-0001-9199-9160
FU NATIONAL EYE INSTITUTE [R24EY015638, R21EY017153, R56EY014240,
   R01EY014240] Funding Source: NIH RePORTER; NEI NIH HHS [R21
   EY017153-01A1, R01 EY014240, EY015638, R21 EY017153, R56 EY014240,
   EY017153, EY014240, R24 EY015638] Funding Source: Medline
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NR 28
TC 5
Z9 5
U1 0
U2 0
PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
J9 EXP EYE RES
JI Exp. Eye Res.
PD JAN
PY 2008
VL 86
IS 1
BP 150
EP 156
DI 10.1016/j.exer.2007.10.006
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 249ED
UT WOS:000252209100017
PM 18036592
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Lang, UE
   Stogowski, D
   Schuze, D
   Domula, M
   Schmidt, E
   Gallinat, J
   Tugtekin, SM
   Felber, W
AF Lang, Undine E.
   Stogowski, Dariusz
   Schuze, Doreen
   Domula, Markus
   Schmidt, Eckart
   Gallinat, Jueergen
   Tugtekin, Sems Malte
   Felber, Werner
TI Charles Bonnet Syndrome: Successful treatment of visual hallucinations
   due to vision loss with selective serotonin reuptake inhibitors
SO JOURNAL OF PSYCHOPHARMACOLOGY
LA English
DT Article
DE serotonin; Charles Bonnet Syndrome; CBS; hallucinations; epileptic;
   SSRI; venlafaxine; escitalopram
ID CITALOPRAM; BRAIN
AB Visual hallucinations are a common and often distressing consequence of vision toss, 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. So far, although this condition is frequent, no established treatment for CBS has been stated. We report here the case of a 78-year-old woman, who came in our hospital because of a 4-week tong mild depressive symptomatology. For 1 year she experienced daily sudden, unexpected, vivid and elaborate hallucinations. Insight was completely present, so the patient stated that the hallucinations were unreal and that the faces, geometrical figures and animals she saw every day were possibly due to her vision loss. The Mini Mental State Examination, digit span and verbal fluency were administered and no cognitive impairment was reported. The visual acuity was hand motion. After 4 days of treatment with venlafaxine the hallucinations completely disappeared. This is the first case to show that selective serotonin (and noradrenalin) reuptake inhibitors may be an effective and well-tolerated treatment for visual hallucinations associated with vision Loss, and it adds to evidence implicating serotonergic pathways in the pathogenesis of visual hallucinations.
C1 Univ Dresden, Dept Psychiat, D-01099 Dresden, Germany.
   Univ Dresden, Dept Ophthalmol, Dresden, Germany.
   Heart Ctr Dresden, Dept Cardiac Surg, Dresden, Germany.
C3 Technische Universitat Dresden; Technische Universitat Dresden;
   Technische Universitat Dresden
RP Lang, UE (通讯作者)，Univ Dresden, Dept Psychiat, Fetscherstr 74, D-01099 Dresden, Germany.
EM undine.lang@gmx.de
RI Lang, Undine Emmi E/K-5553-2015
OI Lang, Undine Emmi E/0000-0002-3585-6533
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NR 19
TC 30
Z9 33
U1 0
U2 11
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0269-8811
J9 J PSYCHOPHARMACOL
JI J. Psychopharmacol.
PD JUL
PY 2007
VL 21
IS 5
BP 553
EP 555
DI 10.1177/0269881106075275
PG 3
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 200WJ
UT WOS:000248793200014
PM 17446204
DA 2022-11-30
ER

PT J
AU Bora, PS
   Kallappan, S
   Lyzogubov, VV
   Tytarenko, RG
   Thotakura, S
   Viswanathan, T
   Bora, NS
AF Bora, Puran S.
   Kallappan, Sankaranarayanan
   Lyzogubov, Valerly V.
   Tytarenko, Ruslana G.
   Thotakura, Sushma
   Viswanathan, Tito
   Bora, Nalini S.
TI Expression of adiponectin in choroidal tissue and inhibition of laser
   induced choroidal neovascularization by adiponectin
SO FEBS LETTERS
LA English
DT Article
DE choroid; neovascularization; angiogenesis; adipocyte; macular
   degeneration and adiponectin
ID MOLECULE T-CADHERIN; INSULIN-RESISTANCE; COMPLEMENT; RECEPTORS; FAT;
   ACRP30/ADIPONECTIN; ACTIVATION; CYTOKINES; GLUCOSE; MUSCLE
AB The aim of this study was to investigate the role of adiponectin (APN) in a mouse model of laser induced choroidal neovascularization (CNV). We have shown by immunohistochemistry that the expression of APN, adiponectin receptor 1, adiponectin receptor 2 and T cadherin gradually increased from day I to day 7 post-laser in laser treated mice compared to controls. Recombinant APN (rAPN) was injected intraperitoneally (i.p., 25 mu g/mouse) or intravitreally (2 mu g/eye) in lasered mice. Another set of lasered mice received APN peptide via i.p. (75 mu g/mouse) or intravitreal (30 mu g/eye) route. Control mice received a similar treatment with PBS, control protein or control peptide after laser treatment. We found that in the i.p. and intravitreal injection of rAPN resulted in 78% and 68% inhibition respectively in the size of CNV complex compared to control mice. Similar results were observed when APN peptide was injected intravitreally or i.p. Treatment with rAPN or the peptide resulted in decreased levels of vascular endothelial growth factor. Thus, APN inhibited choroidal angiogenesis and may have therapeutic implications in the treatment of wet age related macular degeneration. 2007 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
C1 Univ Arkansas Med Sci, Dept Ophthalmol, Jones Eye Inst, Pat & Willard Walker Eye Res Ctr, Little Rock, AR 72205 USA.
   Univ Arkansas, Dept Chem, Little Rock, AR 72204 USA.
C3 University of Arkansas System; University of Arkansas Medical Sciences;
   University of Arkansas System; University of Arkansas Fayetteville;
   University of Arkansas Little Rock
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
CR AMIN R, 1994, INVEST OPHTH VIS SCI, V35, P3178
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NR 39
TC 31
Z9 41
U1 0
U2 1
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-5793
EI 1873-3468
J9 FEBS LETT
JI FEBS Lett.
PD MAY 15
PY 2007
VL 581
IS 10
BP 1977
EP 1982
DI 10.1016/j.febslet.2007.04.024
PG 6
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 171IF
UT WOS:000246728700008
PM 17466298
OA Bronze
DA 2022-11-30
ER

PT J
AU Krebs, I
   Binder, S
   Stolba, U
   Brunner, S
AF Krebs, I
   Binder, S
   Stolba, U
   Brunner, S
TI Reading ability and central visual field after photodynamic therapy
SO OPHTHALMOLOGICA
LA English
DT Article
DE age-related macular degeneration; photodynamic therapy; reading acuity;
   static threshold perimetry; subfoveal choroidal neovascularization
   verteporphin; Visudyne (R)
ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; LASER
   PHOTOCOAGULATION; VERTEPORFIN; ACUITY; EYES
AB Purpose: We examined whether photodynamic therapy (PDT) can prevent severe loss of reading acuity and further depression of the visual field in cases of predominantly classic subfoveal neovascularization due to age-related macular degeneration. Patients and Methods: Sixty eyes of 52 patients underwent biomicroscopy, assessment of reading and distance acuity, 10degrees static threshold perimetry, distance acuity, and fluorescein angiography at baseline, after 6 weeks, 3 months and then every 3 months after therapy. Results: After 18 months only 16.7% had lost more than 3 levels of reading acuity, 23.3% had lost less than 3 levels, 6.7% had remained unchanged and 53.3% had gained reading acuity, 18.7% of these more than 3 levels. 81.7% of the eyes lost less than 3 lines of distance acuity. 78.3% did not show any increase of the mean defect in the central visual field. Conclusion: PDT can prevent severe loss of distance and reading acuity and further deterioration of the central visual field in about 80% of the eyes. The baseline reading acuity was poor and the patients should be aware of the fact that loss of reading acuity cannot be regained even after successful PDT. Copyright (C) 2004 S. Karger AG, Basel.
C1 Ludwig Boltzman Inst Retinol & Biomciroscop Surg, Rudolf Fdn Clin, Dept Ophthalmol, AT-1030 Vienna, Austria.
C3 Ludwig Boltzmann Institute
RP Krebs, I (通讯作者)，Ludwig Boltzman Inst Retinol & Biomciroscop Surg, Rudolf Fdn Clin, Dept Ophthalmol, Juchgasse 25, AT-1030 Vienna, Austria.
EM Ilse.Krebs@wienkav.at
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NR 28
TC 10
Z9 10
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3755
J9 OPHTHALMOLOGICA
JI Ophthalmologica
PY 2004
VL 218
IS 3
BP 185
EP 192
DI 10.1159/000076843
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 814KT
UT WOS:000220974300005
PM 15103215
DA 2022-11-30
ER

PT J
AU Bhardwaj, T
   Jha, SK
AF Bhardwaj, Tanu
   Jha, Sandeep Kumar
TI On-Line PAT Monitoring of Lucentis in the Fermenter Using Aptamer-Based
   Capacitive Microfluidic Chip Biosensor
SO JOURNAL OF THE ELECTROCHEMICAL SOCIETY
LA English
DT Article
ID RANIBIZUMAB; TECHNOLOGY
AB In this study, we have developed an aptamer-based PDMS/glass microfluidic chip biosensor employing the capacitance based method of detection, which has the tendency to work as an on-line Process Analytical Technology (PAT) monitoring tool to detect Lucentis in the fermenters. The limit of detection (LOD) and linear range of detection of the chip was determined to be 8.5 nM and 8.5-100 nM, respectively which was better than HPLC based method of Lucentis estimation. In real sample analysis, a significant correlation was obtained between the reported microchip based biosensor and HPLC-based detection method. Moreover, pre-concentration or pre-processing of media broth was not necessary with our method, which reduced the analysis time to 30 min. The chip was determined to be miniaturized, selective, specific, interference-free, label-free, rapid, and reusable with a long shelf-life. Additionally, the chip demonstrated the requirement of a small direct sample volume of 10 mu l and simple automation using a peristaltic pump. The chip biosensor is expected to have on-line PAT monitoring use for checking the production of Lucentis in the fermenter leading to a reduction in the cost of the therapy and better affordability of the treatment to the age-related macular degeneration (AMD) patients.
C1 [Bhardwaj, Tanu; Jha, Sandeep Kumar] Indian Inst Technol, Ctr Biomed Engn, New Delhi 110016, India.
C3 Indian Institute of Technology System (IIT System); Indian Institute of
   Technology (IIT) - Delhi
RP Jha, SK (通讯作者)，Indian Inst Technol, Ctr Biomed Engn, New Delhi 110016, India.
EM sandeepjha@iitd.ac.in
FU Department of Science & Technology SERB grant [EMR/2015/002354];
   Department of Biotechnology, Ministry of Science and Technology [BT/
   COE/34/SP15097/2015]
FX The work was supported partially through Department of Science &
   Technology SERB grant no. EMR/2015/002354 and Department of
   Biotechnology, Ministry of Science and Technology grant number BT/
   COE/34/SP15097/2015.
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NR 29
TC 0
Z9 0
U1 4
U2 4
PU ELECTROCHEMICAL SOC INC
PI PENNINGTON
PA 65 SOUTH MAIN STREET, PENNINGTON, NJ 08534 USA
SN 0013-4651
EI 1945-7111
J9 J ELECTROCHEM SOC
JI J. Electrochem. Soc.
PD MAY 1
PY 2022
VL 169
IS 5
AR 057512
DI 10.1149/1945-7111/ac5799
PG 11
WC Electrochemistry; Materials Science, Coatings & Films
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Electrochemistry; Materials Science
GA 1J1DN
UT WOS:000797664900001
DA 2022-11-30
ER

PT J
AU Ahani-Nahayati, M
   Niazi, V
   Moradi, A
   Pourjabbar, B
   Roozafzoon, R
   Baradaran-Rafii, A
   Keshel, SH
AF Ahani-Nahayati, Milad
   Niazi, Vahid
   Moradi, Alireza
   Pourjabbar, Bahareh
   Roozafzoon, Reza
   Baradaran-Rafii, Alireza
   Keshel, Saeed Heidari
TI Cell-based Therapy for Ocular Disorders: A Promising Frontier
SO CURRENT STEM CELL RESEARCH & THERAPY
LA English
DT Review
DE Ocular diseases; cell-based therapy; regenerative medicine; stem cell;
   multipotent stem cells; pluripotent stem
ID MESENCHYMAL STEM-CELLS; AMNIOTIC MEMBRANE TRANSPLANTATION; VESICLES
   PROMOTE NEUROPROTECTION; RETINAL GANGLION-CELLS; LONG-TERM SAFETY;
   NEUROMYELITIS-OPTICA; RETINITIS-PIGMENTOSA; MACULAR DEGENERATION;
   EPITHELIAL-CELLS; MOUSE MODEL
AB As the ocular disorders causing the long-term blindness or optical abnormalities of the ocular tissue entirely affect life quality, an insight into their corresponding pathogenesis and the expansion of attitudes authorizing earlier detection and treatment need more consideration. Though current therapeutics result in desirable outcomes, they do not offer an inclusive solution for hindrance of development of visual impairment to blindness. Accordingly, stem cells because of their particular competencies have attracted pronounced attention to be applied in regenerative medicine of ocular diseases. In the last decades, a wide spectrum of stem cells surrounding Mesenchymal Stem/Stromal Cells (MSC), Neural Stem Cells (NSCs), and embryonic/induced pluripotent stem cells (ESCs/iPSCs) accompanied by Muller glia, ciliary epithelia-derived stem cells, and Retinal Pigment Epithelial (RPE) stem cells have been widely investigated to report their safety and efficacy in preclinical models and also human subjects. In this regard and the first interventions, RPE cell suspensions were successfully utilized to ameliorate visual defects of the patients suffering from Age-related Macular Degeneration (AMD) after subretinal transplantation. Herein, we will explain the pathogenesis of ocular diseases and highlight the novel discoveries and recent findings in the context of stem cell-based therapies in these disorders, focusing on the last decade's in vivo reports.
C1 [Ahani-Nahayati, Milad; Niazi, Vahid; Pourjabbar, Bahareh; Roozafzoon, Reza; Keshel, Saeed Heidari] Shahid Beheshti Univ Med Sci, Sch Adv Technol Med, Dept Tissue Engn & Appl Cell Sci, Tehran, Iran.
   [Moradi, Alireza] Iran Univ Med Sci, Sch Med, Dept Physiol, Tehran, Iran.
   [Roozafzoon, Reza; Keshel, Saeed Heidari] Shahid Beheshti Univ Med Sci, Med Nanotechnol Res Ctr, Tehran, Iran.
   [Ahani-Nahayati, Milad; Baradaran-Rafii, Alireza] Shahid Beheshti Univ Med Sci, Ophthalm Res Ctr, Tehran, Iran.
C3 Shahid Beheshti University Medical Sciences; Iran University of Medical
   Sciences; Shahid Beheshti University Medical Sciences; Shahid Beheshti
   University Medical Sciences
RP Keshel, SH (通讯作者)，Shahid Beheshti Univ Med Sci, Sch Adv Technol Med, Dept Tissue Engn & Appl Cell Sci, Tehran, Iran.; Keshel, SH (通讯作者)，Shahid Beheshti Univ Med Sci, Med Nanotechnol Res Ctr, Tehran, Iran.
EM Saeedhey@gmail.com
RI Niazi, Vahid/CAF-4738-2022; Heidari keshel, Saeed/M-5936-2016
OI Heidari keshel, Saeed/0000-0003-2637-2825; pourjabbar,
   bahareh/0000-0001-8632-0475
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NR 140
TC 1
Z9 1
U1 1
U2 7
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 1574-888X
EI 2212-3946
J9 CURR STEM CELL RES T
JI Curr. Stem Cell Res. Ther.
PY 2022
VL 17
IS 2
BP 147
EP 165
DI 10.2174/1574888X16666210622124555
PG 19
WC Cell & Tissue Engineering; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA YL7NK
UT WOS:000746075100004
PM 34161213
DA 2022-11-30
ER

PT J
AU Ho, AC
   Kleinman, DM
   Lum, FC
   Heier, JS
   Lindstrom, RL
   Orr, SC
   Chang, GC
   Smith, EL
   Pollack, JS
AF Ho, Allen C.
   Kleinman, David M.
   Lum, Flora C.
   Heier, Jeffrey S.
   Lindstrom, Richard L.
   Orr, Susan C.
   Chang, Grace C.
   Smith, Eleanor L.
   Pollack, John S.
TI Baseline Visual Acuity at Wet AMD Diagnosis Predicts Long-Term Vision
   Outcomes: An Analysis of the IRIS Registry
SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA
LA English
DT Article
ID MACULAR DEGENERATION; RANIBIZUMAB; BEVACIZUMAB; MULTICENTER
AB BACKGROUND AND OBJECTIVE: Clinical trials in neovascular age-related macular degeneration (nAMD) demonstrate that high visual acuity (VA) can be maintained, and low VA can be improved with anti-vascular endothelial growth factor (VEGF) treatment. Few real-world data investigating the relationship between baseline VA and long-term outcomes exist. This study compares VA at diagnosis and after treatment using data from a large patient registry.
   PATIENTS AND METHODS: Retrospective study of IRIS Registry patients diagnosed with nAMD in one or both eyes between January 2013 and June 2017. Patients received at least two anti-VEGF injections in the study eye(s) less than 45 days apart during the study period. Primary outcomes were the percentage of eyes with 20/40 VA or better at diagnosis and association of VA at diagnosis with longer-term visual outcomes.
   RESULTS: The study included 162.902 eyes. Among all included eyes, 34.3% presented with 20/40 VA or better at diagnosis. Patients with 20/40 vision or better at baseline maintained a mean VA of 20/40 or better for 2 years after treatment initiation.
   CONCLUSIONS: Baseline. VA at nAMD diagnosis predicts long-term VA outcomes. Early diagnosis before VA is adversely affected is a key factor in preserving vision in patients with nAMD.
C1 [Ho, Allen C.] Wills Eye Hosp & Res Inst, Retina Serv, 10th Floor,840 Walnut St, Philadelphia, PA 19107 USA.
   [Kleinman, David M.] Univ Rochester, Rochester, NY USA.
   [Lum, Flora C.] Amer Acad Ophthalmol, San Francisco, CA USA.
   [Heier, Jeffrey S.] Ophthalm Consultants Boston, Boston, MA USA.
   [Lindstrom, Richard L.] Minnesota Eye Consultants, Bloomington, MN USA.
   [Orr, Susan C.; Chang, Grace C.] Notal Vis, Manassas, VA USA.
   [Smith, Eleanor L.] Beacon Clin Consultants, Portland, ME USA.
   [Pollack, John S.] Illinois Retina Associates, Chicago, IL USA.
C3 Jefferson University; University of Rochester; Ophthalmic Consultants of
   Boston
RP Ho, AC (通讯作者)，Wills Eye Hosp & Res Inst, Retina Serv, 10th Floor,840 Walnut St, Philadelphia, PA 19107 USA.
EM achomd@gmail.com
OI Ho, Allen/0000-0003-3921-608X
FU Notal Vision
FX Notal Vision supported the conduct of the study and provided editorial
   and writing assistance.
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TC 5
Z9 5
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 NOV
PY 2020
VL 51
IS 11
BP 633
EP 639
DI 10.3928/23258160-20201104-05
PG 7
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA PA2RK
UT WOS:000595480800005
PM 33231696
OA hybrid
DA 2022-11-30
ER

PT J
AU Lin, FL
   Wang, PY
   Chuang, YF
   Wang, JH
   Wong, VHY
   Bui, BV
   Liu, GS
AF Lin, Fan-Li
   Wang, Peng-Yuan
   Chuang, Yu-Fan
   Wang, Jiang-Hui
   Wong, Vickie H. Y.
   Bui, Bang, V
   Liu, Guei-Sheung
TI Gene Therapy Intervention in Neovascular Eye Disease: A Recent Update
SO MOLECULAR THERAPY
LA English
DT Review
ID ENDOTHELIAL GROWTH-FACTOR; EPITHELIUM-DERIVED FACTOR; PRECLINICAL SAFETY
   EVALUATION; MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; IN-VIVO;
   OCULAR NEOVASCULARIZATION; DIABETIC-RETINOPATHY; TARGETING VEGF; CORNEAL
   NEOVASCULARIZATION
AB Aberrant growth of blood vessels (neovascularization) is a key feature of severe eye diseases that can cause legal blindness, including neovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR). The development of anti-vascular endothelial growth factor (VEGF) agents has revolutionized the treatment of ocular neovascularization. Novel proangiogenic targets, such as angiopoietin and platelet-derived growth factor (PDGF), are under development for patients who respond poorly to anti-VEGF therapy and to reduce adverse effects from long-term VEGF inhibition. A rapidly advancing area is gene therapy, which may provide significant therapeutic benefits. Viral vector-mediated transgene delivery provides the potential for continuous production of antiangiogenic proteins, which would avoid the need for repeated anti-VEGF injections. Gene silencing with RNA interference to target ocular angiogenesis has been investigated in clinical trials. Proof-of-concept gene therapy studies using gene-editing tools such as CRISPR-Cas have already been shown to be effective in suppressing neovascularization in animal models, highlighting the therapeutic potential of the system for treatment of aberrant ocular angiogenesis. This review provides updates on the development of anti-VEGF agents and novel antiangiogenic targets. We also summarize current gene therapy strategies already in clinical trials and those with the latest approaches utilizing CRISPR-Cas gene editing against aberrant ocular neovascularization.
C1 [Lin, Fan-Li; Wang, Peng-Yuan; Chuang, Yu-Fan] Chinese Acad Sci, Shenzhen Key Lab Biomimet Mat & Cellular Immunomo, Shenzhen Inst Adv Technol, 1068 Xueyuan Ave, Shenzhen 518055, Guangdong, Peoples R China.
   [Lin, Fan-Li; Chuang, Yu-Fan; Liu, Guei-Sheung] Univ Tasmania, Menzies Inst Med Res, 17 Liverpool St, Hobart, Tas 7000, Australia.
   [Wang, Peng-Yuan] Swinburne Univ Technol, Dept Chem & Biotechnol, Hawthorn, Vic 3122, Australia.
   [Wang, Jiang-Hui] Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, East Melbourne, Vic 3002, Australia.
   [Wong, Vickie H. Y.; Bui, Bang, V] Univ Melbourne, Dept Optometry & Vis Sci, Parkville, Vic 3010, Australia.
   [Liu, Guei-Sheung] Univ Melbourne, Ophthalmol, Dept Surg, East Melbourne, Vic 3002, Australia.
C3 Chinese Academy of Sciences; Shenzhen Institute of Advanced Technology,
   CAS; University of Tasmania; Menzies Institute for Medical Research;
   Swinburne University of Technology; Centre for Eye Research Australia;
   Royal Victorian Eye & Ear Hospital; University of Melbourne; University
   of Melbourne
RP Wang, PY (通讯作者)，Chinese Acad Sci, Shenzhen Key Lab Biomimet Mat & Cellular Immunomo, Shenzhen Inst Adv Technol, 1068 Xueyuan Ave, Shenzhen 518055, Guangdong, Peoples R China.; Liu, GS (通讯作者)，Univ Tasmania, Menzies Inst Med Res, 17 Liverpool St, Hobart, Tas 7000, Australia.
EM py.wang@siat.ac.cn; rickliu0817@gmail.com
RI Bui, Bang/AAD-2679-2021; Liu, Guei-Sheung/Q-6472-2018
OI Bui, Bang/0000-0001-7298-1352; Liu, Guei-Sheung/0000-0003-3379-724X;
   Lin, Fan-Li/0000-0001-8348-9873
FU National Health and Medical Research Council of Australia [GNT1185600];
   Ophthalmic Research Institute of Australia; Shenzhen Key Laboratory of
   Biomimetic Materials and Cellular Immunomodulation
   [ZDSYS20190902093409851]; Victorian Government
FX This work was supported by grants from the National Health and Medical
   Research Council of Australia (GNT1185600), the Ophthalmic Research
   Institute of Australia, and the Shenzhen Key Laboratory of Biomimetic
   Materials and Cellular Immunomodulation (ZDSYS20190902093409851). The
   Centre for Eye Research Australia receives Operational Infrastructure
   Support from the Victorian Government.
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NR 230
TC 15
Z9 16
U1 4
U2 30
PU CELL PRESS
PI CAMBRIDGE
PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD OCT 7
PY 2020
VL 28
IS 10
BP 2120
EP 2138
DI 10.1016/j.ymthe.2020.06.029
PG 19
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 OD0HW
UT WOS:000579536500007
PM 32649860
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Chung, SH
   Mollhoff, IN
   Nguyen, U
   Nguyen, A
   Stucka, N
   Tieu, E
   Manna, S
   Meleppat, RK
   Zhang, PF
   Nguyen, EL
   Fong, J
   Zawadzki, R
   Yiu, G
AF Chung, Sook Hyun
   Mollhoff, Iris Natalie
   Nguyen, Uyen
   Nguyen, Amy
   Stucka, Natalie
   Tieu, Eric
   Manna, Suman
   Meleppat, Ratheesh Kumar
   Zhang, Pengfei
   Nguyen, Emerald Lovece
   Fong, Jared
   Zawadzki, Robert
   Yiu, Glenn
TI Factors Impacting Efficacy of AAV-Mediated CRISPR-Based Genome Editing
   for Treatment of Choroidal Neovascularization
SO MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; GEOGRAPHIC ATROPHY;
   VEGF EXPRESSION; GENE; DELIVERY; RETINOPATHY; INJECTION; MODEL; CAS9
AB Frequent injections of anti-vascular endothelial growth factor (anti-VEGF) agents are a clinical burden for patients with neo-vascular age-related macular degeneration (AMD). Genomic disruption of VEGF-A using adeno-associated viral (AAV) delivery of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 has the potential to permanently suppress aberrant angiogenesis, but the factors that determine the optimal efficacy are unknown. Here, we investigate two widely used Cas9 endonucleases, SpCas9 and SaCas9, and evaluate the relative contribution of AAV-delivery efficiency and genome-editing rates in vivo to determine the mechanisms that drive successful CRISPR-based suppression of VEGF-A, using a mouse model of laser-induced choroidal neovascularization (CNV). We found that SpCas9 demonstrated higher genome-editing rates, greater VEGF reduction, and more effective CNV suppression than SaCas9, despite similar AAV transduction efficiency between a dual-vector approach for SpCas9 and single-vector system for SaCas9 to deliver the Cas9 orthologs and single guide RNAs (gRNAs). Our results suggest that successful VEGF knockdown using AAV-mediated CRISPR systems may be determined more by the efficiency of genome editing rather than viral transduction and that SpCas9 may be more effective than SaCas9 as a potential therapeutic strategy for CRISPR-based treatment of CNV in neovascular AMD.
C1 [Chung, Sook Hyun; Mollhoff, Iris Natalie; Nguyen, Uyen; Nguyen, Amy; Stucka, Natalie; Tieu, Eric; Manna, Suman; Meleppat, Ratheesh Kumar; Zhang, Pengfei; Nguyen, Emerald Lovece; Fong, Jared; Zawadzki, Robert; Yiu, Glenn] Univ Calif Davis, Dept Ophthalmol & Vis Sci, Davis, CA 95616 USA.
C3 University of California System; University of California Davis
RP Yiu, G (通讯作者)，Univ Calif Davis, Dept Ophthalmol & Vis Sci, Davis, CA 95616 USA.
EM gyiu@ucdavis.edu
RI Zhang, Pengfei/G-8826-2019; Zawadzki, Robert J./S-3236-2019; Meleppat,
   Ratheesh Kumar/AAG-4806-2020
OI Zhang, Pengfei/0000-0003-4437-8112; Zawadzki, Robert
   J./0000-0002-9574-156X; Meleppat, Ratheesh Kumar/0000-0003-0240-9419
FU NIH (Bethesda, MD) [K08 EY026101, R21 EY031108, R01 026556]; E. Matilda
   Ziegler Foundation for the Blind (Darien, CT); Barr Foundation for
   Retinal Research (Sacramento, CA); ARVO Foundation (Rockville, MD);
   Alcon Research Institute (Geneva, Switzerland); Macula Society
   (Beachwood, OH); NIH [P30 EY012576]
FX This study was supported by NIH (Bethesda, MD) K08 EY026101, R21
   EY031108, and R01 026556; the E. Matilda Ziegler Foundation for the
   Blind (Darien, CT); the Barr Foundation for Retinal Research
   (Sacramento, CA); the ARVO Foundation (Rockville, MD); the Alcon
   Research Institute (Geneva, Switzerland); and the Macula Society
   (Beachwood, OH). Histological and ultrastructural studies were conducted
   at the Center for Vision Sciences (CVS) Structure-Function core
   facility; AAV production was conducted at the CVS Molecular Packaging
   and Construct core facility, and in vivo mouse imaging was conducted at
   the CVS "EyePod" Small Animal Ocular Imaging Laboratory, which are
   supported by NIH P30 EY012576. No funding organizations had any role in
   the design or conduct of this research. The content is solely the
   responsibility of the authors and does not necessarily represent the
   official views of the funding agencies.
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NR 52
TC 14
Z9 14
U1 4
U2 19
PU CELL PRESS
PI CAMBRIDGE
PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
EI 2329-0501
J9 MOL THER-METH CLIN D
JI Mol.Ther.-Methods Clin. Dev.
PD JUN 12
PY 2020
VL 17
BP 409
EP 417
DI 10.1016/j.omtm.2020.01.006
PG 9
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA LZ0FC
UT WOS:000540906400037
PM 32128346
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Touhami, S
   Beguier, F
   Augustin, S
   Charles-Messance, H
   Vignaud, L
   Nandrot, EF
   Reichman, S
   Forster, V
   Mathis, T
   Sahel, JA
   Bodaghi, B
   Guillonneau, X
   Sennlaub, F
AF Touhami, Sara
   Beguier, Fanny
   Augustin, Sebastien
   Charles-Messance, Hugo
   Vignaud, Lucile
   Nandrot, Emeline F.
   Reichman, Sacha
   Forster, Valerie
   Mathis, Thibaud
   Sahel, Jose-Alain
   Bodaghi, Bahram
   Guillonneau, Xavier
   Sennlaub, Florian
TI Chronic exposure to tumor necrosis factor alpha induces retinal pigment
   epithelium cell dedifferentiation
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
DE Retinal pigment epithelium; Tumor necrosis factor alpha; Transforming
   growth factor beta; Age-related macular degeneration; Neuroinflammation;
   Neurodegenerative disease
ID MACULAR DEGENERATION; TNF-ALPHA; AGE; INFLAMMATION; EXPRESSION;
   CYTOKINES; ACTIVATION; MICROGLIA; DISEASE; MICE
AB Background: The retinal pigment epithelium (RPE) is a monolayer of pigmented cells with important barrier and immuno-suppressive functions in the eye. We have previously shown that acute stimulation of RPE cells by tumor necrosis factor alpha (TNF alpha) downregulates the expression of OTX2 (Orthodenticle homeobox 2) and dependent RPE genes. We here investigated the long-term effects of TNF alpha on RPE cell morphology and key functions in vitro.
   Methods: Primary porcine RPE cells were exposed to TNF alpha (at 0.8, 4, or 20 ng/ml per day) for 10 days. RPE cell morphology, phagocytosis, barrier-and immunosuppressive-functions were assessed.
   Results: Chronic (10 days) exposure of primary RPE cells to TNF alpha increases RPE cell size and polynucleation, decreases visual cycle gene expression, impedes RPE tight-junction organization and transepithelial resistance, and decreases the immunosuppressive capacities of the RPE. TNF alpha-induced morphological-and transepithelial-resistance changes were prevented by concomitant Transforming Growth Factor beta inhibition.
   Conclusions: Our results indicate that chronic TNF alpha-exposure is sufficient to alter RPE morphology and impede cardinal features that define the differentiated state of RPE cells with striking similarities to the alterations that are observed with age in neurodegenerative diseases such as age-related macular degeneration.
C1 [Touhami, Sara; Beguier, Fanny; Augustin, Sebastien; Charles-Messance, Hugo; Vignaud, Lucile; Nandrot, Emeline F.; Reichman, Sacha; Forster, Valerie; Mathis, Thibaud; Sahel, Jose-Alain; Guillonneau, Xavier; Sennlaub, Florian] Sorbonne Univ, CNRS, INSERM, Inst Vis, 17 Rue Moreau, F-75012 Paris, France.
   [Touhami, Sara; Bodaghi, Bahram] Univ Paris VI, Hop Pitie Salpetriere, Dept Ophthalmol, DHU Sight Restore,Reference Ctr Rare Dis, 47-83 Blvd Hop, F-75013 Paris, France.
   [Sahel, Jose-Alain] INSERM, DGOS CIC 1423, DHU Sight Restore, CHNO Quinze Vingts, 28 Rue Charenton, F-75012 Paris, France.
C3 Centre National de la Recherche Scientifique (CNRS); Institut National
   de la Sante et de la Recherche Medicale (Inserm); UDICE-French Research
   Universities; Sorbonne Universite; Universite Paris Cite; Assistance
   Publique Hopitaux Paris (APHP); Hopital Universitaire Pitie-Salpetriere
   - APHP; UDICE-French Research Universities; Sorbonne Universite; CHNO
   des Quinze-Vingts; Institut National de la Sante et de la Recherche
   Medicale (Inserm); UDICE-French Research Universities; Sorbonne
   Universite
RP Touhami, S (通讯作者)，Sorbonne Univ, CNRS, INSERM, Inst Vis, 17 Rue Moreau, F-75012 Paris, France.; Touhami, S (通讯作者)，Univ Paris VI, Hop Pitie Salpetriere, Dept Ophthalmol, DHU Sight Restore,Reference Ctr Rare Dis, 47-83 Blvd Hop, F-75013 Paris, France.
EM saratouhami@gmail.com
RI Guillonneau, xavier/E-3995-2017; Mathis, Thibaud/AAK-5745-2021; Mathis,
   Thibaud/R-3696-2016; Bodaghi, Bahram/AAS-1160-2021; Sahel,
   Jose-Alain/F-3172-2017; Nandrot, Emeline F./AAN-3925-2020; Touhami,
   Sara/AAF-7836-2021; Reichman, Sacha/R-7581-2017; Sennlaub,
   Florian/F-2756-2017; guillonneau, xavier/AAF-9495-2021; Beguier,
   Fanny/AAY-8581-2020
OI Guillonneau, xavier/0000-0001-7379-3935; Mathis,
   Thibaud/0000-0002-1418-1872; Sahel, Jose-Alain/0000-0002-4831-1153;
   Reichman, Sacha/0000-0003-1776-6339; Sennlaub,
   Florian/0000-0003-4412-1341; guillonneau, xavier/0000-0001-7379-3935;
   Beguier, Fanny/0000-0002-6123-2978; Michaelides,
   Michel/0000-0002-1552-7046; Nandrot, Emeline/0000-0003-3087-078X
FU INSERM; ANR Geno [R09099DS]; ANR MACLEAR [ANR-15-CE14-0015-01]; LABEX
   LIFESENSES - ANR [ANR-10-LABX-65, ANR-11-IDEX0004-02]
FX This work was supported by grants from INSERM, ANR Geno 2009 (R09099DS),
   ANR MACLEAR (ANR-15-CE14-0015-01), LABEX LIFESENSES [ANR-10-LABX-65]
   supported by the ANR (Investissements d'Avenir programme
   [ANR-11-IDEX0004-02]), and a generous donation by Doris and Michael
   Bunte.
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SN 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD MAR 16
PY 2018
VL 15
AR 85
DI 10.1186/s12974-018-1106-8
PG 11
WC Immunology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology; Neurosciences & Neurology
GA FZ9BN
UT WOS:000427904700002
PM 29548329
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Ang, M
   Tan, ACS
   Cheung, CMG
   Keane, PA
   Dolz-Marco, R
   Sng, CCA
   Schmetterer, L
AF Ang, Marcus
   Tan, Anna C. S.
   Cheung, Chui Ming Gemmy
   Keane, Pearse A.
   Dolz-Marco, Rosa
   Sng, Chelvin C. A.
   Schmetterer, Leopold
TI Optical coherence tomography angiography: a review of current and future
   clinical applications
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Review
DE Optical coherence tomography; Angiography; Vascularisation; Retina;
   Glaucoma; Cornea
ID INDOCYANINE GREEN ANGIOGRAPHY; FOVEAL AVASCULAR ZONE;
   DIABETIC-RETINOPATHY; FLUORESCEIN ANGIOGRAPHY; CHOROIDAL
   NEOVASCULARIZATION; IMAGE ARTIFACTS; CORNEAL; DENSITY; RETINA; EYES
AB Optical coherence tomography angiography is a non-invasive imaging technique that now allows for simultaneous in vivo imaging of the morphology as well as the vasculature in the eye. In this review, we provide an update on the existing clinical applications of optical coherence tomography angiography technology from the anterior to posterior segment of the eye. We also discuss the limitations of optical coherence tomography angiography technology, as well as the caveats to the interpretation of images. As current optical coherence tomography angiography systems are optimized for the retina, most studies have focused on interpreting images from conditions such as age related macular degeneration and retinal vascular diseases. However, the interpretation of these optical coherence tomography angiography images should be taken in consideration with other multi-modal imaging to overcome the limitations of each technique. In addition, there are a growing variety of clinical applications for optical coherence tomography angiography imaging in optic nerve head evaluation for glaucoma and optic neuropathies. Further developments in anterior optical coherence tomography angiography have now allowed for evaluation of anterior segment pathology such as glaucoma, ocular surface diseases, corneal vascularisation, and abnormal iris vasculature. Future developments in software could allow for improved segmentation and image resolution with automated measurements and analysis.
C1 [Ang, Marcus; Tan, Anna C. S.; Cheung, Chui Ming Gemmy] Singapore Natl Eye Ctr, 11 Third Hosp Ave, Singapore 168751, Singapore.
   [Ang, Marcus; Tan, Anna C. S.; Cheung, Chui Ming Gemmy; Schmetterer, Leopold] Duke NUS Med Sch, Singapore, Singapore.
   [Ang, Marcus; Tan, Anna C. S.; Cheung, Chui Ming Gemmy; Sng, Chelvin C. A.; Schmetterer, Leopold] Singapore Eye Res Inst, Singapore, Singapore.
   [Ang, Marcus; Keane, Pearse A.; Sng, Chelvin C. A.] Moorfields Eye Hosp, London, England.
   [Keane, Pearse A.] UCL, Inst Ophthalmol, London, England.
   [Dolz-Marco, Rosa] FISABIO Ophthalm Med, Valencia, Spain.
   [Sng, Chelvin C. A.] Natl Univ Hlth Syst, Singapore, Singapore.
   [Schmetterer, Leopold] Nanyang Technol Univ, Lee Kong Med Sch, Singapore, Singapore.
   [Schmetterer, Leopold] Med Univ Vienna, Ctr Med Phys & Biomed Engn, Vienna, Austria.
   [Schmetterer, Leopold] Med Univ Vienna, Dept Clin Pharmacol, Vienna, Austria.
C3 Singapore National Eye Center; National University of Singapore;
   National University of Singapore; Singapore National Eye Center;
   University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; University of London; University College London;
   National University of Singapore; Nanyang Technological University &
   National Institute of Education (NIE) Singapore; Nanyang Technological
   University; Medical University of Vienna; Medical University of Vienna
RP Ang, M (通讯作者)，Singapore Natl Eye Ctr, 11 Third Hosp Ave, Singapore 168751, Singapore.; Ang, M (通讯作者)，Duke NUS Med Sch, Singapore, Singapore.; Ang, M (通讯作者)，Singapore Eye Res Inst, Singapore, Singapore.; Ang, M (通讯作者)，Moorfields Eye Hosp, London, England.
EM marcus.ang@snec.com.sg
RI Keane, Pearse/AAE-5709-2019
OI Keane, Pearse/0000-0002-9239-745X; Sng, Chelvin/0000-0002-9837-6019;
   Cheung, Chui Ming Gemmy/0000-0003-3358-3516; Schmetterer,
   Leopold/0000-0002-7189-1707
FU Department of Health [CS-2014-14-023] Funding Source: Medline; National
   Institute for Health Research [CS-2014-14-023] Funding Source:
   researchfish
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NR 61
TC 91
Z9 98
U1 12
U2 54
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 FEB
PY 2018
VL 256
IS 2
BP 237
EP 245
DI 10.1007/s00417-017-3896-2
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FU2WB
UT WOS:000423709600001
PM 29318383
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Koc, F
   Erden, V
   Sefi-Yurdakul, N
AF Koc, Feray
   Erden, Veysi
   Sefi-Yurdakul, Nazife
TI Causes of low vision and blindness in a Turkish adult population: the
   Izmir eye study
SO EASTERN MEDITERRANEAN HEALTH JOURNAL
LA English
DT Article
DE Blindness; low vision; adults; Izmir
ID PREVALENCE
AB Background: Data from Turkey show that sense organ diseases were the second leading cause of years lost due to disability in 2015. However, there are no reliable data on either the baseline causative disorders of visual impairment or the burden of these disorders on the population in Izmir region. Izmir is the third most populated city of Turkey with a population of approximately 4.2 million.
   Aim: The purpose of this study was to define the baseline disorders causing low vision and blindness in accordance with World Health Organization criteria in an adult population in Izmir.
   Methods: We evaluated the ophthalmologic reports of 20 790 people in Izmir, Turkey. Age- and sex-specific causes of low vision and blindness were identified.
   Results: Bilateral low vision and blindness was detected in 347 people, 172 males and 175 females. For those aged 18-50 years, retinal dystrophies (37%), congenital eye anomalies (14%) and myopic degenerations (13%) were the most common causes. For those aged 50+years, age-related macular degeneration (21%) was the leading cause. Diabetic retinopathy (17%), corneal opacities (14%), cataract (12%) and glaucoma (9%) were also important. Sex was not a significant determinant.
   Conclusion: The specific causes of visual impairment vary greatly with age, however, unavoidable retinal pathologies were the predominant causes at all ages.
C1 [Koc, Feray; Erden, Veysi] Izmir Ataturk Educ & Res Hosp, Izmir, Turkey.
   [Sefi-Yurdakul, Nazife] Baskent Univ, Izmir, Turkey.
C3 Izmir Ataturk Training & Research Hospital; Baskent University
RP Koc, F (通讯作者)，Izmir Ataturk Educ & Res Hosp, Izmir, Turkey.
EM dr_feray@yahoo.com
RI Koc, Filiz/A-9125-2017; Yurdakul, Nazife Sefi/AAF-4678-2020
OI Yurdakul, Nazife Sefi/0000-0003-2005-9256
CR [Anonymous], 2002, ANK STAT I STAT PRES
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NR 23
TC 5
Z9 5
U1 0
U2 0
PU WHO EASTERN MEDITERRANEAN REGIONAL OFFICE
PI NASR CITY, CAIRO
PA P. O. BOX 7608, NASR CITY, CAIRO, EGYPT
SN 1020-3397
EI 1687-1634
J9 E MEDITERR HEALTH J
JI East Mediterr. Health J.
PD FEB
PY 2018
VL 24
IS 2
BP 161
EP 168
DI 10.26719/2018.24.2.161
PG 8
WC Health Care Sciences & Services; Health Policy & Services; Public,
   Environmental & Occupational Health
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Health Care Sciences & Services; Public, Environmental & Occupational
   Health
GA GI6LK
UT WOS:000434481700007
PM 29748945
OA Bronze
DA 2022-11-30
ER

PT J
AU Tian, B
   Al-Moujahed, A
   Bouzika, P
   Hu, YJ
   Notomi, S
   Tsoka, P
   Miller, JW
   Lin, HJ
   Vavvas, DG
AF Tian, Bo
   Al-Moujahed, Ahmad
   Bouzika, Peggy
   Hu, Yijun
   Notomi, Shoji
   Tsoka, Pavlina
   Miller, Joan W.
   Lin, Haijiang
   Vavvas, Demetrios G.
TI Atorvastatin Promotes Phagocytosis and Attenuates Pro-Inflammatory
   Response in Human Retinal Pigment Epithelial Cells
SO SCIENTIFIC REPORTS
LA English
DT Article
ID LOW-DENSITY-LIPOPROTEIN; BLOOD-BRAIN-BARRIER; MACULAR DEGENERATION;
   IN-VITRO; STATINS; CHOLESTEROL; PROGRESSION; SIMVASTATIN; INHIBITION;
   PROTEIN
AB Phagocytosis of daily shed photoreceptor outer segments is an important function of the retinal pigment epithelium (RPE) and it is essential for retinal homeostasis. RPE dysfunction, especially impairment of its phagocytic ability, plays an essential role in the pathogenesis of age-related macular degeneration (AMD). Statins, or HMG CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, are drugs with multiple properties that have been extensively used to treat hyperlipidemia. However, their effect on RPE cells has not been fully elucidated. Here we report that high dose atorvastatin increased the phagocytic function of ARPE-19 cells, as well as rescue the cells from the phagocytic dysfunction induced by cholesterol crystals and oxidized low-density lipoproteins (ox-LDL), potentially by increasing the cellular membrane fluidity. Similar effects were observed when evaluating two other hydrophobic statins, lovastatin and simvastatin. Furthermore, atorvastatin was able to block the induction of interleukins IL-6 and IL-8 triggered by pathologic stimuli relevant to AMD, such as cholesterol crystals and ox-LDL. Our study shows that statins, a well-tolerated class of drugs with rare serious adverse effects, help preserve the phagocytic function of the RPE while also exhibiting anti-inflammatory properties. Both characteristics make statins a potential effective medication for the prevention and treatment of AMD.
C1 [Tian, Bo; Al-Moujahed, Ahmad; Bouzika, Peggy; Notomi, Shoji; Tsoka, Pavlina; Miller, Joan W.; Lin, Haijiang; Vavvas, Demetrios G.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Angiogenesis Lab,Retina Serv, Boston, MA 02114 USA.
   [Al-Moujahed, Ahmad] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA.
   [Hu, Yijun] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China.
   [Lin, Haijiang] Univ Massachusetts, Med Sch, Dept Ophthalmol & Visual Sci, Worcester, MA 01605 USA.
C3 Harvard University; Harvard Medical School; Massachusetts Eye & Ear
   Infirmary; Boston University; Sun Yat Sen University; University of
   Massachusetts System; University of Massachusetts Worcester
RP Lin, HJ; Vavvas, DG (通讯作者)，Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Angiogenesis Lab,Retina Serv, Boston, MA 02114 USA.; Lin, HJ (通讯作者)，Univ Massachusetts, Med Sch, Dept Ophthalmol & Visual Sci, Worcester, MA 01605 USA.
EM Haijiang_Lin@meei.harvard.edu; Demetrios_Vavvas@meei.harvard.edu
RI Hu, Yijun/J-4044-2016
OI Miller, Joan/0000-0003-2046-3996; Lin, Haijiang/0000-0003-2931-468X;
   Vavvas, Demetrios/0000-0002-8622-6478; /0000-0002-5435-8804; Hu,
   Yijun/0000-0002-6424-7905
FU NEI [R21EY023079-01A1, EY014104]; Yeatts Family Foundation; Loefflers
   Family Fund; Macula Society Research Grant award; Physician Scientist
   Award; research to prevent blindness foundation; NATIONAL EYE INSTITUTE
   [R01EY025362, R21EY023079] Funding Source: NIH RePORTER
FX This work was supported by: NEI R21EY023079-01A1 (D.G.V.); the Yeatts
   Family Foundation (D.G.V., J.W.M.); the Loefflers Family Fund (D.G.V.,
   J.W.M.); the 2013 Macula Society Research Grant award (D.G.V.); a
   Physician Scientist Award (D.G.V.), an unrestricted grant (J.W.M.) from
   the research to prevent blindness foundation; NEI grant EY014104 (Meei
   Core Grant).
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NR 70
TC 18
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U1 1
U2 3
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD MAY 24
PY 2017
VL 7
AR 2329
DI 10.1038/s41598-017-02407-7
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA FX2RR
UT WOS:000425909700002
PM 28539592
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Mao, XY
   Fang, WY
   Liu, QH
AF Mao, Xiying
   Fang, Wangyi
   Liu, Qinghuai
TI An Emerging Role of Alu RNA in Geographic Atrophy Pathogenesis: the
   Implication for Novel Therapeutic Strategies
SO DISCOVERY MEDICINE
LA English
DT Article
ID NLRP3 INFLAMMASOME ACTIVATION; OXIDATIVE STRESS; MACULAR DEGENERATION;
   CELL-DEATH; RETINAL DYSTROPHIES; MITOCHONDRIAL-DNA; GENE-REGULATION;
   KAPPA-B; APOPTOSIS; CASPASE-8
AB It is generally accepted that geographic atrophy (GA), a currently untreatable advanced form of age-related macular degeneration (AMD), is a multifactorial disease resulting in gradual and permanent blindness. Various risk factors are demonstrated to be responsible for its pathogenesis, such as aging, light exposure, and smoking. Molecular components associated with those risk factors form a complex and interwoven network at the confluence of inflammation, highlighting the significance of inflammasome activation in GA progression. Recently, a new type of modification in AMD microenvironment has been discovered, other than extensively-studied complement dysregulation, lipofuscin deposit, and oxidative by-products, to activate inflammasome. The accumulation of Alu RNA, resulting from DICER1 deficiency, is shown capable of triggering the activation of NLRP3 inflammasome and causing caspase-8-activated apoptosis in an IL-18/MyD88-dependent manner, which provides a new source of evidence for the interplay between cell death and inflammasome. In this review, we lay the emphasis on the mechanism by which Alu RNA activates NLRP3 inflammasome and downstream apoptotic proteins, and on its clinical relevance to GA and potential therapeutic approaches. We also point out several possible crosstalks among inflammasome and different acts of cell death which remain to be further investigated in Alu RNA-induced RPE degeneration.
C1 [Mao, Xiying; Fang, Wangyi; Liu, Qinghuai] Nanjing Med Univ, Dept Ophthalmol, Affiliated Hosp 1, Nanjing 210029, Jiangsu, Peoples R China.
C3 Nanjing Medical University
RP Liu, QH (通讯作者)，Nanjing Med Univ, Dept Ophthalmol, Affiliated Hosp 1, Nanjing 210029, Jiangsu, Peoples R China.
EM liuqh@njmu.edu.cn
OI Liu, Qinghuai/0000-0003-1605-1964
FU National Basic Research Program ("973" Program) of China [2013CB967500,
   2011CB65102]
FX This work was supported by grants from the National Basic Research
   Program ("973" Program) of China (2013CB967500, 2011CB65102).
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NR 91
TC 7
Z9 8
U1 0
U2 3
PU DISCOVERY MEDICINE
PI TIMONIUM
PA 10 GERARD AVE, STE 201, TIMONIUM, MD 21093 USA
SN 1539-6509
EI 1944-7930
J9 DISCOV MED
JI Discov. Med.
PD DEC
PY 2016
VL 22
IS 123
BP 337
EP 349
PG 13
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA ES4IL
UT WOS:000399497300002
PM 28147216
DA 2022-11-30
ER

PT J
AU Arteni, AA
   Fradot, M
   Galzerano, D
   Mendes-Pinto, MM
   Sahel, JA
   Picaud, S
   Robert, B
   Pascal, AA
AF Arteni, Ana-Andreea
   Fradot, Mathias
   Galzerano, Denise
   Mendes-Pinto, Maria M.
   Sahel, Jose-Alain
   Picaud, Serge
   Robert, Bruno
   Pascal, Andrew A.
TI Structure and Conformation of the Carotenoids in Human Retinal Macular
   Pigment
SO PLOS ONE
LA English
DT Article
ID LIGHT-HARVESTING PROTEINS; IN-VIVO; BINDING-PROTEIN; PHOTOSYSTEM-II;
   HIGHER-PLANTS; ZEAXANTHIN; MECHANISM; LUTEIN; PHOTOPROTECTION;
   IDENTIFICATION
AB Human retinal macular pigment (MP) is formed by the carotenoids lutein and zeaxanthin (including the isomer meso-zeaxanthin). MP has several functions in improving visual performance and protecting against the damaging effects of light, and MP levels are used as a proxy for macular health-specifically, to predict the likelihood of developing age-related macular degeneration. While the roles of these carotenoids in retinal health have been the object of intense study in recent years, precise mechanistic details of their protective action remain elusive. We have measured the Raman signals originating from MP carotenoids in ex vivo human retinal tissue, in order to assess their structure and conformation. We show that it is possible to distinguish between lutein and zeaxanthin, by their excitation profile (related to their absorption spectra) and the position of their V-1 Raman mode. In addition, analysis of the V-4 Raman band indicates that these carotenoids are present in a specific, constrained conformation in situ, consistent with their binding to specific proteins as postulated in the literature. We discuss how these conclusions relate to the function of these pigments in macular protection. We also address the possibilities for a more accurate, consistent measurement of MP levels by Raman spectroscopy.
C1 [Arteni, Ana-Andreea; Galzerano, Denise; Mendes-Pinto, Maria M.; Robert, Bruno; Pascal, Andrew A.] Univ Paris Saclay, CEA, UMR CNRS 8221, Inst Integrat Biol Cell I2BC, Gif Sur Yvette, France.
   [Arteni, Ana-Andreea; Galzerano, Denise; Mendes-Pinto, Maria M.; Robert, Bruno; Pascal, Andrew A.] Univ Paris Saclay, CEA, UMR CNRS 8221, Inst Biol & Technol Saclay, Gif Sur Yvette, France.
   [Fradot, Mathias; Sahel, Jose-Alain; Picaud, Serge] INSERM, UMR S968, Inst Vis, Paris, France.
C3 CEA; Centre National de la Recherche Scientifique (CNRS); UDICE-French
   Research Universities; Universite Paris Saclay; CEA; Centre National de
   la Recherche Scientifique (CNRS); UDICE-French Research Universities;
   Universite Paris Saclay; Institut National de la Sante et de la
   Recherche Medicale (Inserm); UDICE-French Research Universities;
   Sorbonne Universite
RP Pascal, AA (通讯作者)，Univ Paris Saclay, CEA, UMR CNRS 8221, Inst Integrat Biol Cell I2BC, Gif Sur Yvette, France.
EM andrew.pascal@cea.fr
RI Sahel, Jose-Alain/F-3172-2017; Arteni, Ana Andreea/AAK-8561-2020; Pinto,
   Maria Manuela Mendes/M-2804-2013; Robert, Bruno/D-1264-2012; Picaud,
   Serge/H-4012-2014; pascal, andrew/B-6186-2014
OI Sahel, Jose-Alain/0000-0002-4831-1153; Robert,
   Bruno/0000-0001-5999-4538; Picaud, Serge/0000-0002-0548-5145; Mendes
   Pinto, Maria Manuela/0000-0001-7541-7335; ARTENI, Ana
   Andreea/0000-0001-6462-905X; pascal, andrew/0000-0002-1844-6065
FU European Research Council [267333]; French Infrastructure for Integrated
   Structural Biology [ANR-10-INSB-05-01]; CEA interdisciplinary program
   Technology for Health (MEDIASPEC project)
FX This work was supported by the European Research Council
   (http://erc.europa.eu/) through the Advanced Grant PHOTPROT (contract
   number 267333, to BR); the French Infrastructure for Integrated
   Structural Biology https://www.structuralbiology.eu/networks/frisbi
   (grant number ANR-10-INSB-05-01, to BR); and the CEA interdisciplinary
   program Technology for Health (MEDIASPEC project, to BR). The funders
   had no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript.
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NR 28
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Z9 21
U1 2
U2 45
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 27
PY 2015
VL 10
IS 8
AR e0135779
DI 10.1371/journal.pone.0135779
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA CP8KZ
UT WOS:000360144000025
PM 26313550
OA gold, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Hanus, J
   Zhang, HM
   Chen, DH
   Zhou, QB
   Jin, P
   Liu, QH
   Wang, SS
AF Hanus, Jakub
   Zhang, Hongmei
   Chen, David H.
   Zhou, Qinbo
   Jin, Peng
   Liu, Qinghua
   Wang, Shusheng
TI Gossypol Acetic Acid Prevents Oxidative Stress-Induced Retinal Pigment
   Epithelial Necrosis by Regulating the FoxO3/Sestrin2 Pathway
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID FOXO TRANSCRIPTION FACTORS; CELL-DEATH; GENE; ANTIOXIDANT; INHIBITOR;
   APOPTOSIS; IDENTIFICATION; INDUCTION; LONGEVITY; SURVIVAL
AB The late stage of dry age-related macular degeneration (AMD), or geographic atrophy (GA), is characterized by extensive retinal pigment epithelial (RPE) cell death, and a cure is not available currently. We have recently demonstrated that RPE cells die from necrosis in response to oxidative stress, providing a potential novel mechanism for RPE death in AMD. In this study, we screened U.S. Food and Drug Administration-approved natural compounds and identified gossypol acetic acid (GAA) as a potent inhibitor of oxidative stress-induced RPE cell death. GAA induces antioxidative response and inhibits accumulation of excessive reactive oxygen species in cells, through which it prevents the activation of intrinsic necrotic pathway in response to oxidative stress. Sestrin2 (SESN2) is found to mediate GAA function in antioxidative response and RPE survival upon oxidative stress. Moreover, Forkhead box O3 transcription factor (FoxO3) is further found to be required for GAA-mediated SESN2 expression and RPE survival. Mechanistically, GAA promotes FoxO3 nuclear translocation and binding to the SESN2 enhancer, which in turn increases its transcriptional activity. Taken together, we have identified GAA as a potent inhibitor of oxidative stress-induced RPE necrosis by regulating the FoxO3/SESN2 pathway. This study may have significant implications in the therapeutics of age-related diseases, especially GA.
C1 [Hanus, Jakub; Chen, David H.; Zhou, Qinbo; Wang, Shusheng] Tulane Univ, Dept Cell & Mol Biol, New Orleans, LA 70118 USA.
   [Wang, Shusheng] Tulane Univ, Dept Ophthalmol, New Orleans, LA 70118 USA.
   [Zhang, Hongmei] Univ Texas SW Med Ctr Dallas, Dept Ophthalmol, Dallas, TX 75390 USA.
   [Liu, Qinghua] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
   [Jin, Peng] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA.
C3 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;
   Emory University
RP Wang, SS (通讯作者)，Tulane Univ, Dept Cell & Mol Biol, New Orleans, LA 70118 USA.
EM swang1@tulane.edu
FU Tulane University, National Institutes of Health [EY021862]; Research to
   Prevent Blindness Foundation; Bright Focus Foundation; NATIONAL EYE
   INSTITUTE [R01EY021862] Funding Source: NIH RePORTER
FX S.W. was supported by a Startup fund from Tulane University, National
   Institutes of Health grant EY021862, a career development award from
   Research to Prevent Blindness Foundation, and a Bright Focus Foundation
   Award in Age-Related Macular Degeneration. D.H.C. was a summer research
   student from the University of Southern California.
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NR 55
TC 17
Z9 17
U1 0
U2 17
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD JUN
PY 2015
VL 35
IS 11
BP 1952
EP 1963
DI 10.1128/MCB.00178-15
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA CH3FI
UT WOS:000353913000006
PM 25802279
OA Green Published
DA 2022-11-30
ER

PT J
AU Segal, O
   Ferencz, JR
   Cohen, P
   Nemet, AY
   Nesher, R
AF Segal, Ori
   Ferencz, Joseph R.
   Cohen, Perri
   Nemet, Arie Y.
   Nesher, Ronit
TI Persistent Elevation of Intraocular Pressure Following Intravitreal
   Injection of Bevacizumab
SO ISRAEL MEDICAL ASSOCIATION JOURNAL
LA English
DT Article
DE age-related macular degeneration (AMD); avastin; bevacizumab; glaucoma;
   intraocular pressure (IOP); intravitreal injection; anti-vascular
   endothelial growth factor (VEGF)
ID TRABECULAR MESHWORK; RANIBIZUMAB; PEGAPTANIB; SECONDARY; EYES
AB Background: The number of patients treated with intravitreal injections has increased significantly over the past few years, mainly following the introduction of anti-vascular endothelial growth factor antibody intraocular drugs. Bevacizumab is mostly used in this group of medications.
   Objectives: To describe persistent elevation of intraocular pressure (IOP) following intravitreal injection of bevacizumab.
   Methods: We reviewed consecutive cases of persistent IOP elevation after intravitreal bevacizumab injection for exudative age-related macular degeneration (AMD). A total of 424 patients (528 eyes) met the inclusion criteria and received 1796 intravitreal injections of bevacizumab. Persistent IOP elevation was found in 19 eyes (3.6%, 19/528) of 18 patients (4.2%, 18/424) with IOP elevated 30-70 mmHg 3-30 days after injection.
   Results: Mean IOP was 42.6 mmHg (range 30-70); IOP elevations occurred after an average of 7.8 injections of bevacizumab (range 3-13). Injected eyes (19/528) had a significantly higher incidence of elevated IOP than uninjected eyes (fellow eyes), 1/328, P < 0.001.
   Conclusions: Like other anti-vascular endothelial growth factor (VEGF) substances reported in a few recent studies, intravitreal injection of bevacizumab for neovascular AMD may be associated with persistent IOP elevation. Providers should be aware that significant IOP elevation might occur after repeated treatments.
C1 Meir Med Ctr, Dept Ophthalmol, Kefar Sava, Israel.
   Tel Aviv Univ, Sackler Fac Med, Ramat Aviv, Israel.
C3 Tel Aviv University; Sackler Faculty of Medicine; Tel Aviv University;
   Sackler Faculty of Medicine
RP Segal, O (通讯作者)，18 Shoham St, IL-69359 Tel Aviv, Israel.
EM orisegal@gmail.com
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NR 19
TC 18
Z9 19
U1 0
U2 1
PU ISRAEL MEDICAL ASSOC JOURNAL
PI RAMAT GAN
PA 2 TWIN TOWERS, 11TH FL, 35 JABOTINSKY ST, PO BOX 3604, RAMAT GAN 52136,
   ISRAEL
SN 1565-1088
J9 ISR MED ASSOC J
JI Isr. Med. Assoc. J.
PD JUL
PY 2013
VL 15
IS 7
BP 352
EP 355
PG 4
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 199WC
UT WOS:000323025200005
PM 23943979
DA 2022-11-30
ER

PT J
AU Bunnik, EM
   Schermer, MHN
   Janssens, ACJW
AF Bunnik, Eline M.
   Schermer, Maartje H. N.
   Janssens, A. Cecile J. W.
TI The role of disease characteristics in the ethical debate on personal
   genome testing
SO BMC MEDICAL GENOMICS
LA English
DT Article
ID RISK; INFORMATION; CHILDREN; ILLNESS; OBESITY; IMPACT; LEGAL
AB Background: Companies are currently marketing personal genome tests directly-to-consumer that provide genetic susceptibility testing for a range of multifactorial diseases simultaneously. As these tests comprise multiple risk analyses for multiple diseases, they may be difficult to evaluate. Insight into morally relevant differences between diseases will assist researchers, healthcare professionals, policy-makers and other stakeholders in the ethical evaluation of personal genome tests.
   Discussion: In this paper, we identify and discuss four disease characteristics - severity, actionability, age of onset, and the somatic/psychiatric nature of disease - and show how these lead to specific ethical issues. By way of illustration, we apply this framework to genetic susceptibility testing for three diseases: type 2 diabetes, age-related macular degeneration and clinical depression. For these three diseases, we point out the ethical issues that are relevant to the question whether it is morally justifiable to offer genetic susceptibility testing to adults or to children or minors, and on what conditions.
   Summary: We conclude that the ethical evaluation of personal genome tests is challenging, for the ethical issues differ with the diseases tested for. An understanding of the ethical significance of disease characteristics will improve the ethical, legal and societal debate on personal genome testing.
C1 [Bunnik, Eline M.; Schermer, Maartje H. N.] Erasmus Univ, Med Ctr, Dept Med Eth & Philosophy Med, NL-3015 GE Rotterdam, Netherlands.
   [Janssens, A. Cecile J. W.] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.
C3 Erasmus University Rotterdam; Erasmus MC; Erasmus University Rotterdam;
   Erasmus MC
RP Bunnik, EM (通讯作者)，Erasmus Univ, Med Ctr, Dept Med Eth & Philosophy Med, Dr Molewaterpl 50, NL-3015 GE Rotterdam, Netherlands.
EM e.bunnik@erasmusmc.nl
OI Bunnik, Eline/0000-0003-1481-6222; Janssens, A
   Cecile/0000-0002-6153-4976; Schermer, Maartje/0000-0003-4283-9659
FU Netherlands Genomics Initiative
FX This text is a result of a research project of the Centre for Society
   and Genomics (CSG) in The Netherlands, funded by the Netherlands
   Genomics Initiative.
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NR 50
TC 22
Z9 23
U1 0
U2 20
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1755-8794
J9 BMC MED GENOMICS
JI BMC Med. Genomics
PD JAN 19
PY 2012
VL 5
AR 4
DI 10.1186/1755-8794-5-4
PG 9
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA 902XC
UT WOS:000301076200002
PM 22260407
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Zerbib, J
   Puche, N
   Richard, F
   Leveziel, N
   Cohen, SY
   Korobelnik, JF
   Sahel, J
   Munnich, A
   Kaplan, J
   Rozet, JM
   Souied, EH
AF Zerbib, Jennyfer
   Puche, Nathalie
   Richard, Florence
   Leveziel, Nicolas
   Cohen, Salomon Y.
   Korobelnik, Jean-Francois
   Sahel, Jose
   Munnich, Arnold
   Kaplan, Josseline
   Rozet, Jean-Michel
   Souied, Eric H.
TI No association between the T280M polymorphism of the CX3CR1 gene and
   exudative AMD
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE AMD; genetic factor; CX3CR1
ID COMPLEMENT FACTOR-H; AGE-RELATED MACULOPATHY; MACULAR DEGENERATION;
   FRENCH POPULATION; R102G POLYMORPHISM; FACTOR-B; RISK; DISEASE;
   SUSCEPTIBILITY; EXPRESSION
AB Major genetic factors for age-related macular degeneration (AMD) have recently been identified as susceptibility risk factors. The CX3CR1 gene has been shown to be associated with AMD in some studies. Our purpose was to analyze the role of the T280M polymorphism of the CX3CR1 gene in a large French population, in a case-control study. 1093 patients with exudative AMD and 396 controls have been recruited and genotyped for the Y402H of CFH, rs10490924 of ARMS2 and T280M of the CX3CR1 gene.The distribution of the Y402H of CFH and of the rs10490924 of ARMS2 was significantly different between cases and controls (p < 0.0001). The distribution of the T280M genotypes was not significantly different in the AMD patients compared to controls (p = 0.99). The Odds Ratio compared to TT individuals was 1.0(95% CI 0.8-1.3) for TM individuals and 1.0(95% CI 0.5-2.1) for MM individuals. The M allele frequency was 0.157 in cases and 0.154 in controls (p = 0.87).
   Our study exclude an association between the T280M of the CX3CR1 gene and exudative AMD in a French population. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Zerbib, Jennyfer; Puche, Nathalie; Leveziel, Nicolas; Souied, Eric H.] Univ Paris Est Creteil, Hop Intercommunal Creteil, Dept Ophthalmol, F-94000 Creteil, France.
   [Zerbib, Jennyfer; Munnich, Arnold; Kaplan, Josseline; Rozet, Jean-Michel] Necker Enfants Malades Hosp, INSERM, U781, Dept Genet, Paris, France.
   [Richard, Florence] Univ Lille Nord France, INSERM, UMR744, Inst Pasteur Lille, Lille, France.
   [Cohen, Salomon Y.] Ophthalmol Ctr Imaging & Laser, Paris, France.
   [Korobelnik, Jean-Francois] Univ Bordeaux 2, CHU Bordeaux, INSERM, U897, F-33076 Bordeaux, France.
   [Sahel, Jose] Univ Paris 06, INSERM, Inst Vis, Paris, France.
   [Souied, Eric H.] Unite Fonct Rech Clin, Creteil, France.
C3 Universite Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil;
   Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire
   Necker-Enfants Malades - APHP; 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); Le Reseau International des Instituts Pasteur (RIIP);
   Universite de Lille - ISITE; Institut Pasteur Lille; Universite de
   Lille; CHU Bordeaux; Institut National de la Sante et de la Recherche
   Medicale (Inserm); UDICE-French Research Universities; Universite de
   Bordeaux; Institut National de la Sante et de la Recherche Medicale
   (Inserm); UDICE-French Research Universities; Sorbonne Universite;
   Assistance Publique Hopitaux Paris (APHP); Universite
   Paris-Est-Creteil-Val-de-Marne (UPEC); Hopital Universitaire
   Henri-Mondor - APHP
RP Souied, EH (通讯作者)，Univ Paris Est Creteil, Hop Intercommunal Creteil, Dept Ophthalmol, 40 Ave Verdun, F-94000 Creteil, France.
EM esouied@hotmail.com
RI KOROBELNIK, Jean-Francois/A-5448-2016; Sahel, Jose-Alain/F-3172-2017;
   ROZET, Jean-Michel/E-5737-2016; KAPLAN, Josseline/I-2622-2017
OI Sahel, Jose-Alain/0000-0002-4831-1153; ROZET,
   Jean-Michel/0000-0001-7951-7886; KAPLAN, Josseline/0000-0002-1849-8658;
   Nicolas, Leveziel/0000-0001-8533-9457
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NR 28
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 OCT
PY 2011
VL 93
IS 4
BP 382
EP 386
DI 10.1016/j.exer.2011.05.005
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 853TZ
UT WOS:000297449900008
PM 21621535
DA 2022-11-30
ER

PT J
AU Francis, PJ
   Schultz, DW
   Gregory, AM
   Schain, MB
   Barra, R
   Majewski, J
   Ott, J
   Acott, T
   Weleber, RG
   Klein, ML
AF Francis, PJ
   Schultz, DW
   Gregory, AM
   Schain, MB
   Barra, R
   Majewski, J
   Ott, J
   Acott, T
   Weleber, RG
   Klein, ML
TI Genetic and phenotypic heterogeneity in pattern dystrophy
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; DOMINANT RETINITIS-PIGMENTOSA;
   PERIPHERIN/RDS GENE; CHOROIDAL NEOVASCULARIZATION; FOVEOMACULAR
   DYSTROPHY; MACULAR DYSTROPHY; RDS GENE; MUTATIONS; FAMILIES; DELETION
AB Background: The pattern dystrophies ( PD) represent a clinically heterogeneous family of inherited macular diseases frequently caused by mutations in the peripherin/ RDS gene. Most previous studies have detailed the clinical findings in single families, making it difficult to derive data from which progression and visual outcome can be generalised.
   Methods: Families were ascertained and clinically evaluated including angiography and electrophysiology where appropriate.
   Results: In each of the six families with autosomal dominant PD, a mutation in the peripherin/ RDS gene was identified, including a novel Cys250Phe variant. These data suggest that the condition is characterised by the accumulation of yellow to grey subretinal flecks, followed by pigmentary change accompanied by patches of chorioretinal atrophy. Subsequently, 50% ( 16/ 32) of individuals with PD developed poor central vision because of chorioretinal geographic atrophy or subretinal neovascularisation. The risk of these complications appears to increase with age.
   Conclusion: PD should not necessarily be considered a benign condition. Instead, patients should be counselled that there is a significant chance of losing central vision in their later years. Some elderly patients with probands showing PD may be misdiagnosed with age related macular degeneration owing to the phenotypic similarities between these conditions in the advanced state.
C1 Oregon Hlth & Sci Univ, Casey Eye Inst, Mol Degenerat Ctr, Portland, OR 97239 USA.
   Guys & St Thomas Hosp, London SE1 7EH, England.
   Rockefeller Univ, New York, NY 10021 USA.
C3 Oregon Health & Science University; Guy's & St Thomas' NHS Foundation
   Trust; Rockefeller University
RP Klein, ML (通讯作者)，Oregon Hlth & Sci Univ, Casey Eye Inst, Mol Degenerat Ctr, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA.
EM kleinm@ohsu.edu
FU NCRR NIH HHS [M01 RR000334, 5 M01 RR000334] Funding Source: Medline; NEI
   NIH HHS [EY012203, R01 EY012203] Funding Source: Medline; NATIONAL
   CENTER FOR RESEARCH RESOURCES [M01RR000334] Funding Source: NIH
   RePORTER; NATIONAL EYE INSTITUTE [R01EY012203] Funding Source: NIH
   RePORTER
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NR 22
TC 57
Z9 65
U1 0
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD SEP
PY 2005
VL 89
IS 9
BP 1115
EP 1119
DI 10.1136/bjo.2004.062695
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 956PW
UT WOS:000231313300014
PM 16113362
OA Green Published, Green Submitted, Bronze
DA 2022-11-30
ER

PT J
AU Xuan, B
   Xu, XR
   Chiou, GCY
   Zhang, YH
   Peng, SX
AF Xuan, B
   Xu, XR
   Chiou, GCY
   Zhang, YH
   Peng, SX
TI Relationship between nitric oxide production and choroidal. blood flow
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID RETINAL FUNCTION RECOVERY; NITROPYRAZOLES; PENETRATION; SCLERA; EYE
AB Purpose: To invent a drug which can specifically facilitate choroid blood flow via increase of nitric oxide (NO). Method: Cell culture was used for in vitro experiments to determine the production of NO by NO donors and colored microsphere technique was used for in vivo experiments to determine the blood flow in various tissues of rabbit eyes. Results: ZX-5 and ZX-4 are two geographic isomers with ZX-5 as trans-form and ZX-4 as cis-form. (1-phenyl-3-{3-methoxy-2-propoxy-5-[4-(3,4,5-trimethoxy-phenyl)-1,3-dithiolane-2-yl{phenyl}thiourea). It was found that ZX-5 released significant amount of NO at 3, 10, 30 mug/ml concentrations and increased choroid blood flow at 1%, 50mul instillation into eyes. It was not effective on the blood flow of iris or ciliary body. The corresponding ZX-4 was not effective on ocular blood flow nor it released NO. Conclusion: ZX-5 can specifically increase the choroidal blood flow which could be useful to suppress the choroidal neovascularization in age-related macular degeneration (AMD). It is hoped that ZX-5 type of compounds could be used for the treatment/prevention of AMD in the elderly.
C1 Texas A&M Univ, Syst Hlth Sci Ctr, Inst Ocular Pharmacol, College Stn, TX 77843 USA.
   Texas A&M Univ, Syst Hlth Sci Ctr, Dept Med Pharmacol & Toxicol, College Stn, TX 77843 USA.
   China Pharmaceut Univ, Ctr Drug Discovery, Nanjing 2100009, Peoples R China.
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; China
   Pharmaceutical University
RP Chiou, GCY (通讯作者)，Texas A&M Univ, Syst Hlth Sci Ctr, Inst Ocular Pharmacol, College Stn, TX 77843 USA.
CR Ambati J, 2000, INVEST OPHTH VIS SCI, V41, P1181
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NR 15
TC 9
Z9 14
U1 0
U2 3
PU MARY ANN LIEBERT INC PUBL
PI LARCHMONT
PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA
SN 1080-7683
J9 J OCUL PHARMACOL TH
JI J. Ocular Pharmacol. Ther.
PD JUN
PY 2003
VL 19
IS 3
BP 247
EP 253
DI 10.1089/108076803321908365
PG 7
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA 687CG
UT WOS:000183357800005
PM 12828842
DA 2022-11-30
ER

PT J
AU Khachik, F
AF Khachik, F
TI An efficient conversion of (3R,3 ' R,6 ' R)-lutein to (3R,3 ' S,6 '
   R)-lutein (3 '-epilutein) and (3R,3 ' R)-zeaxanthin
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Article
ID STRUCTURALLY RELATED-COMPOUNDS; ACTIVE NATURAL CAROTENOIDS; UNSATURATED
   ALCOHOLS; OXIDATION-PRODUCTS; IDENTIFICATION; ELUCIDATION; EXTRACTS;
   LUTEIN; METABOLITES; ZEAXANTHIN
AB Two dietary carotenoids, (3R,3'R,6'R)-lutein (1) and (3R,3R)-zeaxanthin (2), and their metabolite (3R,3'S,6'R)-lutein (3'-epilutein) (3) accumulate in human serum, milk, and ocular tissues. There is increasing evidence that compounds 1 and 2 play an important role in the prevention of age-related macular degeneration. Therefore, the availability of these carotenoids for metabolic studies and clinical trials is essential. Compound 1 is isolated from extracts of marigold flowers (Tagete erecta) and is commercially available, whereas 2 is only accessible by a lengthy total synthesis, and a viable method for synthesis of 3 has not yet been developed. This report describes an efficient conversion of technical grade 1 to 2 via 3. Acid-catalyzed epimerization of 1 yields an equimolar mixture of diastereomers 1 and 3. The mixture was separated by enzyme-mediated acylation with lipase AK from Pseudomonas fluorescens that preferentially esterified 3 and after alkaline hydrolysis yielded this carotenoid in 90% diastereomeric excess (de). Compound 3 was also separated from 1 in 56-88% de by solvent extraction and low-temperature crystallization, Soxhlet extraction, or supercritical fluid extraction. Base-catalyzed isomerization of 3 gave 2 in excellent yield, providing a convenient alternative to the total synthesis of this important dietary carotenoid.
C1 Univ Maryland, JIFSAN, Dept Chem & Biochem, College Pk, MD 20742 USA.
C3 University System of Maryland; University of Maryland College Park
RP Khachik, F (通讯作者)，Univ Maryland, JIFSAN, Dept Chem & Biochem, College Pk, MD 20742 USA.
EM fk17@umail.umd.edu
RI Khachik, Frederick/C-5055-2009
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NR 35
TC 25
Z9 27
U1 0
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
EI 1520-6025
J9 J NAT PROD
JI J. Nat. Prod.
PD JAN
PY 2003
VL 66
IS 1
BP 67
EP 72
DI 10.1021/np020376l
PG 6
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED); Current Chemical Reactions (CCR-EXPANDED)
SC Plant Sciences; Pharmacology & Pharmacy
GA 639HX
UT WOS:000180623400015
PM 12542348
DA 2022-11-30
ER

PT J
AU Shaban, H
   Borras, C
   Vina, J
   Richter, C
AF Shaban, H
   Borras, C
   Vina, J
   Richter, C
TI Phosphatidylglycerol potently protects human retinal pigment epithelial
   cells against apoptosis induced by A2E, a compound suspected to cause
   age-related macula degeneration
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE age-related macular degeneration; A2E; apoptosis; cardiolipin; coenzyme
   Q; cytochrome c; cytochrome c oxidase; light-induced damage; oxidative
   stress; phosphatidylglycerol; reactive nitrogen species; reactive oxygen
   species; retinal pigment epithelial cells
ID PERFORMANCE LIQUID-CHROMATOGRAPHY; N-RETINYLIDENE ETHANOLAMINE;
   LIPOFUSCIN FLUOROPHORE; OXIDIZED GLUTATHIONE; DAMAGE; BIOSYNTHESIS; ABCR
AB Age-related macular degeneration (AMD) affects about one fifth of the population older than 65 years and is one of the main causes of poor vision in the elderly in industrialized nations. The endogenous lipophilic and cationic compound N-retinyl-N-retinylidene ethanolamine (A2E) is suspected to cause the dry form of the disease, which currently cannot be treated. The authors recently reported that A2E induces apoptosis in several cell types including porcine retinal pigment epithelial cells, detaches proapoptotic proteins from mitochondria, and inhibits cytochrome c oxidase. A2E acts primarily at the level of cardiolipin/cytochrome c oxidase, which in the light becomes permanently inactivated by A2E. The authors now report that A2E at low concentrations causes apoptosis in cultured human retinal pigment epithelial cells. These cells are more sensitive to A2E in the light than in the dark. Phosphatidylglycerol, a negatively charged phospholipid and immediate biosynthetic precursor of cardiolipin readily inhibits apoptosis. Exposure of cells to A2E results in the formation of reactive oxygen and nitrogen species, and exposure of mitochondria to A2E results in oxidative stress. Accordingly, the potent antioxidant coenzyme Q also protects cells against A2E-induced apoptosis, These findings are highly relevant for the treatment and/or prevention of AMD. (C) 2002 Elsevier Science Ltd.
C1 Swiss Fed Inst Technol, Swiss Fed Inst Technol, Inst Biochem, CH-8092 Zurich, Switzerland.
   Fac Med, Dept Fisiol, ES-46010 Valencia, Spain.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Richter, C (通讯作者)，Swiss Fed Inst Technol, Swiss Fed Inst Technol, Inst Biochem, Univ Str 16, CH-8092 Zurich, Switzerland.
EM richter@bc.biol.ethz.ch
RI shaban, Hamdy/C-1939-2014; Vina, Jose/AAB-3069-2021; Shaban,
   Hamdy/ABD-5617-2021
OI shaban, Hamdy/0000-0003-3760-6113; Vina, Jose/0000-0001-9709-0089;
   Shaban, Hamdy/0000-0003-3760-6113; Borras, Consuelo/0000-0003-4606-1792
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NR 23
TC 29
Z9 34
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 JUL
PY 2002
VL 75
IS 1
BP 99
EP 108
DI 10.1006/exer.2001.1192
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 600UK
UT WOS:000178410000010
PM 12123641
DA 2022-11-30
ER

PT J
AU Saptarshi, N
   Porter, LF
   Paraoan, L
AF Saptarshi, Neil
   Porter, Louise F.
   Paraoan, Luminita
TI PERK/EIF2AK3 integrates endoplasmic reticulum stress-induced apoptosis,
   oxidative stress and autophagy responses in immortalised retinal pigment
   epithelial cells
SO SCIENTIFIC REPORTS
LA English
DT Article
ID CYSTATIN-C; PERK; ACTIVATION; SURVIVAL; NRF2; RPE; CONTRIBUTES;
   MECHANISMS; PROTECTS; EFFECTOR
AB Retinal pigment epithelium (RPE) performs essential functions for ensuring retinal homeostasis and is a key site for pathogenic changes leading to age-related macular degeneration (AMD). Compromised proteostasis in RPE results in ER stress and ER stress-dependent antioxidant, apoptosis and autophagic responses. ER stress induces the unfolded protein response (UPR) in which EIF2AK3, encoding the protein kinase RNA-like ER kinase (PERK), acts as a key regulator. Downregulated EIF2AK3 gene expression has recently been identified in AMD using human donor RPE, however the molecular mechanisms that integrate the various ER-mediated cellular pathways underpinning progressive RPE dysfunction in AMD have not been fully characterised. This study investigated the downstream effects of PERK downregulation in response to Brefeldin A (BFA)-induced ER stress in ARPE-19 cells. PERK downregulation resulted in increased ER stress and impaired apoptosis induction, antioxidant responses and autophagic flux. ARPE-19 cells were unable to efficiently induce autophagy following PERK downregulation and PERK presented a role in regulating the rate of autophagy induction. The findings support PERK downregulation as an integrative event facilitating dysregulation of RPE processes critical to cell survival known to contribute to AMD development and highlight PERK as a potential future therapeutic target for AMD.
C1 [Saptarshi, Neil; Porter, Louise F.; Paraoan, Luminita] Univ Liverpool, Inst Life Course & Med Sci, Dept Eye & Vis Sci, Liverpool, Merseyside, England.
   [Porter, Louise F.] Univ Strasbourg, Lab Genet Med, Inst Genet Med Alsace, INSERM U1112,Federat Med Translat Strasbourg FMTS, Strasbourg, France.
   [Porter, Louise F.] Ctr Reference Affect Rares Genet Ophtalmol CARGO, Serv Genet Med, Inst Genet Med Alsace, Strasbourg, France.
   [Paraoan, Luminita] Edge Hill Univ, Dept Biol, Fac Arts & Sci, Ormskirk, England.
C3 University of Liverpool; Institut National de la Sante et de la
   Recherche Medicale (Inserm); UDICE-French Research Universities;
   Universites de Strasbourg Etablissements Associes; Universite de
   Strasbourg; Edge Hill University
RP Porter, LF; Paraoan, L (通讯作者)，Univ Liverpool, Inst Life Course & Med Sci, Dept Eye & Vis Sci, Liverpool, Merseyside, England.; Porter, LF (通讯作者)，Univ Strasbourg, Lab Genet Med, Inst Genet Med Alsace, INSERM U1112,Federat Med Translat Strasbourg FMTS, Strasbourg, France.; Porter, LF (通讯作者)，Ctr Reference Affect Rares Genet Ophtalmol CARGO, Serv Genet Med, Inst Genet Med Alsace, Strasbourg, France.; Paraoan, L (通讯作者)，Edge Hill Univ, Dept Biol, Fac Arts & Sci, Ormskirk, England.
EM lfporter@liverpool.ac.uk; luminita.paraoan@edgehill.ac.uk
RI Paraoan, Luminita/K-1066-2016; Porter, Louise/GQP-6108-2022
OI Paraoan, Luminita/0000-0001-7568-7116; 
FU Academy of Medical Sciences; National Eye Research Centre PhD
   Studentship
FX This project was funded by Academy of Medical Sciences Starter Grant for
   Clinical Lecturers awarded to L.F.P with L.P. as academic supervisor.
   N.S. was supported by a National Eye Research Centre PhD Studentship.
   L.F.P. was an NIHR Clinical Lecturer at the University of Liverpool. The
   views expressed are those of the authors and not necessarily those of
   the NHS, the NIHR, or the Department of Health. The funders had no role
   in the design, data collection, analysis, or conclusions drawn from this
   study.
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NR 53
TC 0
Z9 0
U1 1
U2 1
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD AUG 3
PY 2022
VL 12
IS 1
AR 13324
DI 10.1038/s41598-022-16909-6
PG 13
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 3N0FI
UT WOS:000835830500067
PM 35922637
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Benet, D
   Pellicer-Valero, OJ
AF Benet, David
   Pellicer-Valero, Oscar J.
TI Artificial intelligence: the unstoppable revolution in ophthalmology
SO SURVEY OF OPHTHALMOLOGY
LA English
DT Review
DE Artificial intelligence; Machine learning; Deep learning; Ophthalmology;
   Retina; Optical coherence tomography; Age-related macular degeneration;
   Diabetic retinopathy; Glaucoma; Retinopathy of prematurity
ID DIABETIC-RETINOPATHY; MACULAR DEGENERATION; AUTOMATED DETECTION;
   VALIDATION; VISION; PREDICTION; DISEASES
AB Artificial intelligence (AI) is an unstoppable force that is starting to permeate all aspects of our society as part of the revolution being brought into our lives (and into medicine) by the digital era, and accelerated by the current COVID-19 pandemic. As the population ages and developing countries move forward, AI-based systems may be a key asset in streamlining the screening, staging, and treatment planning of sight-threatening eye conditions, offloading the most tedious tasks from the experts, allowing for a greater population coverage, and bringing the best possible care to every patient. This paper presents a review of the state of the art of AI in the field of ophthalmology, focusing on the strengths and weaknesses of current systems, and defining the vision that will enable us to advance scientifically in this digital era. It starts with a thorough yet accessible introduction to the algorithms underlying all modern AI applications. Then, a critical review of the main AI applications in ophthalmology is presented, including diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, glaucoma, and other AI-related topics such as image enhancement. The review finishes with a brief discussion on the opportunities and challenges that the future of this field might hold. (c) 2021 Elsevier Inc. All rights reserved..
C1 [Pellicer-Valero, Oscar J.] Univ Valencia UV, ETSE Engn Sch, Dept Elect Engn, Intelligent Data Anal Lab, Valencia, Spain.
C3 University of Valencia
RP Benet, D (通讯作者)，Calle Montseny 28, Barcelona 08192, Spain.
EM davidbenetferrus@gmail.com
RI Ruperez, Maria Jose/K-5240-2014; Pellicer-Valero, Oscar Jose/E-3114-2019
OI Ruperez, Maria Jose/0000-0001-8457-7963; Pellicer-Valero, Oscar
   Jose/0000-0002-0104-1029
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NR 76
TC 9
Z9 9
U1 3
U2 19
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 JAN-FEB
PY 2022
VL 67
IS 1
BP 252
EP 270
DI 10.1016/j.survophthal.2021.03.003
EA DEC 2021
PG 19
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA XT2FE
UT WOS:000733409100017
PM 33741420
DA 2022-11-30
ER

PT J
AU Zhao, C
   Kam, HT
   Chen, Y
   Gong, GY
   Hoi, MPM
   Skalicka-Wozniak, K
   Dias, ACP
   Lee, SMY
AF Zhao, Chen
   Kam, Hio-Tong
   Chen, Yan
   Gong, Guiyi
   Hoi, Maggie Pui-Man
   Skalicka-Wozniak, Krystyna
   Dias, Alberto Carlos Pires
   Lee, Simon Ming-Yuen
TI Crocetin and Its Glycoside Crocin, Two Bioactive Constituents From
   Crocus sativus L. (Saffron), Differentially Inhibit Angiogenesis by
   Inhibiting Endothelial Cytoskeleton Organization and Cell Migration
   Through VEGFR2/SRC/FAK and VEGFR2/MEK/ERK Signaling Pathways
SO FRONTIERS IN PHARMACOLOGY
LA English
DT Article
DE crocetin; crocin; angiogenesis; VEGF; zebrafish; HUVEC
ID PHARMACOKINETIC PROPERTIES; IN-VITRO; GROWTH; MECHANISMS; TOXICITY;
   TUMOR
AB Crocetin and crocin are two important carotenoids isolated from saffron (Crocus sativus L.), which have been used as natural biomedicines with beneficial effects for improving the suboptimal health status associated with abnormal angiogenesis. However, the anti-angiogenic effects and underlying mechanisms of the effects of crocetin and crocin have not been investigated and compared. The anti-angiogenic effects of crocetin and crocin were tested on human umbilical vein endothelial cells (HUVECs) in vitro, and in zebrafish in vivo. In vivo, crocetin (20 mu M) and crocin (50 and 100 mu M) significantly inhibited subintestinal vein vessels formation, and a conversion process between them existed in zebrafish, resulting in a difference in their effective concentrations. In the HUVEC model, crocetin (10, 20 and 40 mu M) and crocin (100, 200 and 400 mu M) inhibited cell migration and tube formation, and inhibited the phosphorylation of VEGFR2 and its downstream pathway molecules. In silico analysis further showed that crocetin had a higher ability to bind with VEGFR2 than crocin. These results suggested that crocetin was more effective than crocin in inhibiting angiogenesis through regulation of the VEGF/VEGFR2 signaling pathway. These compounds, especially crocetin, are potential candidate natural biomedicines for the management of diseases associated with abnormal blood vessel growth, such as age-related macular degeneration.
C1 [Zhao, Chen; Kam, Hio-Tong; Chen, Yan; Gong, Guiyi; Hoi, Maggie Pui-Man; Lee, Simon Ming-Yuen] Univ Macau, State Key Lab Qual Res Chinese Med, Macau, Peoples R China.
   [Zhao, Chen; Kam, Hio-Tong; Chen, Yan; Gong, Guiyi; Hoi, Maggie Pui-Man; Lee, Simon Ming-Yuen] Univ Macau, Inst Chinese Med Sci, Macau, Peoples R China.
   [Skalicka-Wozniak, Krystyna] Med Univ Lublin, Dept Pharmacognosy, Independent Lab Nat Prod Chem, Lublin, Poland.
   [Dias, Alberto Carlos Pires] Univ Minho, Dept Biol, AgroBioPlant Grp, Ctr Res & Technol Agroenvironm & Biol Sci CITAB U, Braga, Portugal.
C3 University of Macau; University of Macau; Medical University of Lublin;
   Universidade do Minho
RP Lee, SMY (通讯作者)，Univ Macau, State Key Lab Qual Res Chinese Med, Macau, Peoples R China.; Lee, SMY (通讯作者)，Univ Macau, Inst Chinese Med Sci, Macau, Peoples R China.
EM simonlee@um.edu.mo
RI Hoi, Maggie Pui Man/AAY-5962-2021
OI Hoi, Maggie Pui Man/0000-0003-2630-3707; lee, Simon Ming
   Yuen/0000-0002-3966-6569; Gong, Guiyi/0000-0002-6495-0545
FU Science and Technology Development Fund, Macau SAR [0058/2019/A1,
   0016/2019/AKP]; University of Macau [MYRG201900105-ICMS]
FX This work was supported by The Science and Technology Development Fund,
   Macau SAR (File no. 0058/2019/A1 and 0016/2019/AKP), and University of
   Macau (MYRG201900105-ICMS).
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Z9 3
U1 0
U2 16
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 1663-9812
J9 FRONT PHARMACOL
JI Front. Pharmacol.
PD APR 30
PY 2021
VL 12
AR 675359
DI 10.3389/fphar.2021.675359
PG 13
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA SB7RT
UT WOS:000650187000001
PM 33995106
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Lafuente, M
   Gonzalez-Herrero, MER
   Villadoniga, SR
   Domingo, JC
AF Lafuente, Maria
   Rodriguez Gonzalez-Herrero, Maria Elena
   Romeo Villadoniga, Stephanie
   Domingo, Joan Carles
TI Antioxidant Activity and Neuroprotective Role of Docosahexaenoic Acid
   (DHA) Supplementation in Eye Diseases That Can Lead to Blindness: A
   Narrative Review
SO ANTIOXIDANTS
LA English
DT Review
DE omega-3 fatty acids; docosahexaenoic acid; glutathione; diabetic macular
   edema; glaucoma; oxidative stress; eye health
AB The objective of this narrative review is to provide updated evidence, based on data from experimental and clinical studies, of the prominent role of omega-3 polyunsaturated fatty acids (n-3 PUFAs) for a number of crucial mechanisms involved in counteracting cell damage induced by oxidative stress in eye diseases. This article is focused on the antioxidant and neuroprotective effects of docosahexaenoic acid (DHA), which have been assessed in different experimental models and clinical studies, particularly in proliferative diabetic retinopathy, age-related macular degeneration and glaucoma that are the most common eye diseases leading to severe vision loss. The mechanisms involved in the role of DHA in protecting human retinal pigment epithelial cells from oxidative stress as well as the interaction with glutathione (GSH) are also described. The review is intended to provide novel and salient findings supporting the rationale of the use of dietary supplementation with high-dose DHA (1050 mg/day) in the form of triglyceride as a potent antioxidant compound for improving the eye health. However, the overall clinical evidence for the use of dietary strategies based on supplementation with n-3 PUFAs in eye diseases linked to oxidative stress other than high-dose DHA triglyceride is both limited and inconsistent.
C1 [Lafuente, Maria; Rodriguez Gonzalez-Herrero, Maria Elena] Hosp Univ Virgen Arrixaca, Serv Ophthalmol, E-30120 Murcia, Spain.
   [Romeo Villadoniga, Stephanie] Complejo Hosp Univ Ferrol, Serv Ophthalmol, E-15405 La Coruna, Spain.
   [Domingo, Joan Carles] Univ Barcelona, Fac Biol, Dept Biochem & Mol Biomed, E-08028 Barcelona, Spain.
C3 Hospital Clinico Universitario Virgen de la Arrixaca; Complejo
   Hospitalario Universitario de Ferrol; University of Barcelona
RP Lafuente, M (通讯作者)，Hosp Univ Virgen Arrixaca, Serv Ophthalmol, E-30120 Murcia, Spain.
EM mariaelenargh@gmail.com; marialafuentelh@gmail.com;
   stephimed@hotmail.com; jcdomingo@ub.edu
RI ; Domingo Pedrol, Joan Carles/A-4856-2019
OI ROMEO VILLADONIGA, STEPHANIE/0000-0002-5194-3709; Domingo Pedrol, Joan
   Carles/0000-0002-6356-0836
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NR 71
TC 7
Z9 8
U1 4
U2 10
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2076-3921
J9 ANTIOXIDANTS-BASEL
JI Antioxidants
PD MAR
PY 2021
VL 10
IS 3
AR 386
DI 10.3390/antiox10030386
PG 13
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Food Science &
   Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Food Science
   & Technology
GA RD2DU
UT WOS:000633296400001
PM 33807538
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Vira, J
   Marchese, A
   Singh, RB
   Agarwal, A
AF Vira, Jayesh
   Marchese, Alessandro
   Singh, Rohan Bir
   Agarwal, Aniruddha
TI Swept-source optical coherence tomography imaging of the retinochoroid
   and beyond
SO EXPERT REVIEW OF MEDICAL DEVICES
LA English
DT Review
DE Swept-source; optical coherence tomography; OCTA; retina; imaging
ID INDOCYANINE GREEN ANGIOGRAPHY; CHOROIDAL NEOVASCULARIZATION;
   SPECTRAL-DOMAIN; SYMPATHETIC OPHTHALMIA; MACULAR DEGENERATION;
   HIGH-SPEED; CHORIOCAPILLARIS; FEATURES
AB Introduction: Swept-source optical coherence tomography (SS-OCT) imaging has ushered in an era of rapid and high-resolution imaging of the retinochoroid that provides detailed patho-anatomy of various layers. Areas covered: In this detailed review, the technology of swept-source imaging including its principles and working has been discussed. The applications of SS-OCT in various conditions including age-related macular degeneration, diabetic retinopathy, pachychoroid spectrum of diseases, and inflammatory vitreoretinal conditions have been elaborated. For each disease, a brief review of literature along with the utility of SS-OCT and optical coherence tomography angiography has been provided with supporting figures. The advantages of SS-OCT over spectral-domain have been discussed if there is sufficient evidence in the literature. Finally, the review summarizes the technological advantages in this field of retinal imaging. Expert opinion: The introduction of SS-OCT in our clinics has added newer devices in our armamentarium that can provide high-quality images of the deep retina and choroid. These advances in medical devices can help in improving our knowledge relating to the pathophysiology of diseases and their evolution. In the near future, rapid and high-resolution imaging may provide real-time volumetric information of the whole retina and the choroid that can be readily used for patient care.
C1 [Vira, Jayesh] Shroff Eye Ctr, Dept Ophthalmol, New Delhi, India.
   [Marchese, Alessandro] Univ Vita Salute San Raffaele, San Raffaele Sci Inst, Dept Ophthalmol, Milan, Italy.
   [Singh, Rohan Bir] Harvard Med Sch, Dept Ophthalmol, Boston, MA 02115 USA.
   [Agarwal, Aniruddha] PGIMER, Adv Eye Ctr, Sect 12, Chandigarh 160012, India.
C3 Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele;
   Harvard University; Harvard Medical School; Post Graduate Institute of
   Medical Education & Research (PGIMER), Chandigarh
RP Agarwal, A (通讯作者)，PGIMER, Adv Eye Ctr, Sect 12, Chandigarh 160012, India.
EM aniruddha9@gmail.com
RI Singh, Rohan/AAJ-6297-2021; Singh, Rohan Bir/AAF-2599-2020
OI Singh, Rohan/0000-0002-2426-3900; Agarwal, Aniruddha/0000-0003-4985-9855
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NR 62
TC 15
Z9 16
U1 0
U2 10
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1743-4440
EI 1745-2422
J9 EXPERT REV MED DEVIC
JI Expert Rev. Med. Devices
PD MAY 3
PY 2020
VL 17
IS 5
BP 413
EP 426
DI 10.1080/17434440.2020.1755256
EA APR 2020
PG 14
WC Engineering, Biomedical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering
GA LK7KM
UT WOS:000527587000001
PM 32275451
DA 2022-11-30
ER

PT J
AU Xu, XZ
   Tang, Y
   Cheng, LB
   Yao, J
   Jiang, Q
   Li, KR
   Zhen, YF
AF Xu, Xiang-zhong
   Tang, Yu
   Cheng, Li-bo
   Yao, Jin
   Jiang, Qin
   Li, Ke-ran
   Zhen, Yun-fang
TI Targeting Keap1 by miR-626 protects retinal pigment epithelium cells
   from oxidative injury by activating Nrf2 signaling
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Retinal pigment epithelium cells; Oxidative injury; Keap1; microRNA-626;
   Nrf2 signaling
ID MACULAR DEGENERATION; NONCODING RNA; MOLECULAR-MECHANISMS; STRESS;
   PATHWAY; PROLIFERATION; GENERATION; MICRORNAS; RADIATION; APOPTOSIS
AB Activation of the NF-E2-related factor 2 (Nrf2) cascade can offer significant protection against oxidative stress in retinal pigment epithelium (RPE) cells. Here, we identified a novel kelch-like ECH-associated protein 1 (Keap1)-targeting microRNA, microRNA-626 (miR-626) that activates Nrf2 signaling. In ARPE-19 cells and primary human RPE cells, ectopic overexpression of miR-626 targeting the 3'-UTR (3'-untranslated region) of Keap1 downregulated its expression, promoting Nrf2 protein stabilization and nuclear translocation, leading to expression of ARE-dependent genes (HO1, NOQ1 and GCLC). Functional studies showed that miR-626 protected RPE cells from hydrogen peroxide (H2O2)-induced oxidative injury. Conversely, miR-626 inhibition induced Keap1 upregulation and Nrf2 cascade inhibition, exacerbating oxidative injury in RPE cells. Further studies demonstrated that miR-626 was ineffective in Keap1-knockout or Nrf2-knockout RPE cells. Importantly, miR-626 also activated Keap1-Nrf2 signaling cascade in human lens epithelial cells (HLECs) and primary human retinal ganglion cells (RGCs), providing protection from H2O2. At last, we show that plasma miR-626 levels are significantly downregulated in age-related macular degeneration (AMD) patients than those in the healthy donors. We conclude that targeting Keap1 by miR-626 protects RPE cells and other ophthalmic cells from oxidative injury via activation of Nrf2 signaling cascade.
C1 [Xu, Xiang-zhong; Tang, Yu; Yao, Jin; Jiang, Qin; Li, Ke-ran] Nanjing Med Univ, Affiliated Eye Hosp, Sch Clin Med 4, 138 Han Zhong Rd, Nanjing 210029, Jiangsu, Peoples R China.
   [Cheng, Li-bo] Nanjing Med Univ, Wuxi Hosp 2, Dept Ophthalmol, Wuxi, Jiangsu, Peoples R China.
   [Zhen, Yun-fang] Soochow Univ, Childrens Hosp, Ctr Diag & Treatment Childrens Bone Dis, Suzhou 215100, Peoples R China.
C3 Nanjing Medical University; Nanjing Medical University; Soochow
   University - China
RP Jiang, Q; Li, KR (通讯作者)，Nanjing Med Univ, Affiliated Eye Hosp, Sch Clin Med 4, 138 Han Zhong Rd, Nanjing 210029, Jiangsu, Peoples R China.; Zhen, YF (通讯作者)，Soochow Univ, Childrens Hosp, Ctr Diag & Treatment Childrens Bone Dis, Suzhou 215100, Peoples R China.
EM Jqin710@vip.sina.com; 1150864285@qq.com; zhenyfsz9@163.com
FU National Natural Science Foundation of China [81570859, 81870679,
   81700859, 81800858, 81670878]; Medical Science and Technology
   Development Project Fund of Nanjing [YKK17273, ZKX17053]; Natural
   Science Foundation of Jiangsu Province [BK20161568, BK20171065];
   innovation team Project Fund of Jiangsu Province [CXTDB2017010]; Social
   Development Project of Jiangsu Science and Technology Department
   [BE2016674]; Science and Technology Development Plan Project Fund of
   Nanjing City [201716007, 201805007, 201803058]
FX This work was generously supported by the grants from the National
   Natural Science Foundation of China (81570859, 81870679, 81700859,
   81800858 and 81670878), grants from the Medical Science and Technology
   Development Project Fund of Nanjing (YKK17273 and ZKX17053), grants from
   Natural Science Foundation of Jiangsu Province (BK20161568 and
   BK20171065), grants from innovation team Project Fund of Jiangsu
   Province (CXTDB2017010), by Social Development Project of Jiangsu
   Science and Technology Department (BE2016674), and by Science and
   Technology Development Plan Project Fund of Nanjing City (201716007,
   201805007 and 201803058).
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TC 26
Z9 28
U1 1
U2 6
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 1
PY 2019
VL 143
BP 387
EP 396
DI 10.1016/j.freeradbiomed.2019.08.024
PG 10
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA JM3QK
UT WOS:000496132900037
PM 31446056
DA 2022-11-30
ER

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AF Blasiak, Janusz
   Watala, Cezary
   Tuuminen, Raimo
   Kivinen, Niko
   Koskela, Ali
   Uusitalo-Jarvinen, Hannele
   Tuulonen, Anja
   Winiarczyk, Mateusz
   Mackiewicz, Jerzy
   Zmorzynski, Szymon
   Filip, Agata
   Kaarniranta, Kai
TI Expression of VEGFA-regulating miRNAs and mortality in wet AMD
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Article
DE age-related macular degeneration; AMD; anti-VEGFA injection; miRNA;
   mortality; wet AMD therapy
ID MACULAR DEGENERATION PATIENTS; INFLAMMATORY RESPONSE; ENDOTHELIAL-CELLS;
   GENE-EXPRESSION; AGE; RISK; MICRORNA-126; ANGIOGENESIS; PROTEOLYSIS;
   GUIDELINES
AB MicroRNAs (miRNAs) regulate gene expression; many of them act in the retinal pigment epithelium (RPE), and RPE degeneration is known to be a critical factor in age-related macular degeneration (AMD). Repeated injections with anti-VEGFA (vascular endothelial growth factor A) are the only effective therapy in wet AMD. We investigated the correlation between the expression of 18 miRNAs involved in the regulation of the VEGFA gene in serum of 76 wet AMD patients and 70 controls. Efficacy of anti-VEGFA treatment was evaluated by counting the number of injections delivered up to 12 years. In addition, we compared the relative numbers of deaths in patient with AMD and control groups. We observed a decreased expression of miR-34-5p, miR-126-3p, miR-145-5p and miR-205-5p in wet AMD patients as compared with controls. These miRNAs are involved in the regulation of angiogenesis, cytoprotection and protein clearance. No miRNA was significantly correlated with the treatment outcome. Wet AMD patients had greater mortality than controls, and their survival was inversely associated with the number of anti-VEGFA injections per year. No association was observed between miRNA expression and mortality. Our study emphasizes the need to clarify the role of miRNA regulation in AMD pathogenesis.
C1 [Blasiak, Janusz] Univ Lodz, Fac Biol & Environm Protect, Dept Mol Genet, Lodz, Poland.
   [Watala, Cezary] Med Univ, Dept Haemostat Disorders, Lodz, Poland.
   [Tuuminen, Raimo] Univ Helsinki, Helsinki Retina Res Grp, Helsinki, Finland.
   [Tuuminen, Raimo] Kymenlaakso Cent Hosp, Dept Ophthalmol, Kotka, Finland.
   [Kivinen, Niko; Koskela, Ali; Kaarniranta, Kai] Univ Eastern Finland, Dept Ophthalmol, Kuopio 70211, Finland.
   [Uusitalo-Jarvinen, Hannele; Tuulonen, Anja] Tampere Univ Hosp, Dept Ophthalmol, Tampere, Finland.
   [Winiarczyk, Mateusz; Mackiewicz, Jerzy] Med Univ Lublin, Dept Vitreoretinal Surg, Lublin, Poland.
   [Zmorzynski, Szymon; Filip, Agata] Med Univ Lublin, Dept Canc Genet, Lublin, Poland.
   [Kaarniranta, Kai] Kuopio Univ Hosp, Dept Ophthalmol, Kuopio, Finland.
C3 University of Lodz; University of Helsinki; University of Eastern
   Finland; Tampere University; Tampere University Hospital; Medical
   University of Lublin; Medical University of Lublin; Kuopio University
   Hospital; University of Eastern Finland
RP Kaarniranta, K (通讯作者)，Univ Eastern Finland, Dept Ophthalmol, Kuopio 70211, Finland.; Kaarniranta, K (通讯作者)，Kuopio Univ Hosp, Kuopio 70211, Finland.
EM kai.kaarniranta@uef.fi
RI Watala, Cezary/ABF-4863-2020; Filip, Agata/O-6383-2018
OI Watala, Cezary/0000-0002-5627-7872; Filip, Agata/0000-0001-7591-5887;
   Winiarczyk, Mateusz/0000-0001-9704-3848; Mackiewicz,
   Jerzy/0000-0003-0984-8908; Zmorzynski, Szymon/0000-0002-2039-2908;
   Blasiak, Janusz/0000-0001-9539-9584
FU Narodowe Centrum Nauki [2017/25/N/NZ5/01875]; Sigrid Juselius
   Foundation; Health Research Council of the Academy of Finland [296840];
   University of Eastern Finland; Kuopio University Hospital [5503743];
   Paivikki ja Sakari Sohlbergin Saatio; Finnish Eye Foundation; Finnish
   Funding Agency for Technology and Innovation
FX Narodowe Centrum Nauki, Grant/Award Number: 2017/25/N/NZ5/01875; Sigrid
   Juselius Foundation; Health Research Council of the Academy of Finland,
   Grant/Award Number: 296840; University of Eastern Finland; Kuopio
   University Hospital, Grant/Award Number: 5503743; Paivikki ja Sakari
   Sohlbergin Saatio; Finnish Eye Foundation; Finnish Funding Agency for
   Technology and Innovation
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NR 62
TC 20
Z9 21
U1 3
U2 9
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 DEC
PY 2019
VL 23
IS 12
BP 8464
EP 8471
DI 10.1111/jcmm.14731
EA OCT 2019
PG 8
WC Cell Biology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine
GA JL9PD
UT WOS:000491204800001
PM 31633290
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Dawel, A
   Wong, TY
   McMorrow, J
   Ivanovici, C
   He, XM
   Barnes, N
   Irons, J
   Gradden, T
   Robbins, R
   Goodhew, SC
   Lane, J
   McKone, E
AF Dawel, Amy
   Wong, Tsz Ying
   McMorrow, Jodie
   Ivanovici, Callin
   He, Xuming
   Barnes, Nick
   Irons, Jessica
   Gradden, Tamara
   Robbins, Rachel
   Goodhew, Stephanie C.
   Lane, Jo
   McKone, Elinor
TI Caricaturing as a General Method to Improve Poor Face Recognition:
   Evidence From Low-Resolution Images, Other-Race Faces, and Older Adults
SO JOURNAL OF EXPERIMENTAL PSYCHOLOGY-APPLIED
LA English
DT Article
DE face recognition; caricature; blur; other-race effect; ageing
ID OWN-AGE BIAS; MEMORY TEST; SPACE; DISTINCTIVENESS; SHAPE;
   IDENTIFICATION; PROSOPAGNOSIA; INDIVIDUALS; INFORMATION; SENSITIVITY
AB There are multiple well-established situations in which humans' face recognition performance is poor, including for low-resolution images, other-race faces, and in older adult observers. Here we show that caricaturing faces-that is, exaggerating their appearance away from an average face-can provide a useful applied method for improving face recognition across all these circumstances. We employ a face-name learning task offering a number of methodological advantages (e.g., valid comparison of the size of the caricature improvement across conditions differing in overall accuracy). Across six experiments, we (a) extend previous evidence that caricaturing can improve recognition of low-resolution (blurred) faces; (b) show for the first time that caricaturing improves recognition and perception of other-race faces; and (c) show for the first time that caricaturing improves recognition in observers across the whole adult life span (testing older adults, M age = 71 years). In size. caricature benefits were at least as large where natural face recognition is poor (other-race, low resolution, older adults) as for the naturally best situation (own-race high-resolution faces in young adults). We discuss potential for practical applicability to improving face recognition in low-vision patients (age-related macular degeneration, bionic eye), security settings (police, passport control), eyewitness testimony, and prosopagnosia.
C1 [Dawel, Amy; Wong, Tsz Ying; McMorrow, Jodie; Ivanovici, Callin; He, Xuming; Barnes, Nick; Irons, Jessica; Gradden, Tamara; Robbins, Rachel; Goodhew, Stephanie C.; Lane, Jo; McKone, Elinor] Australian Natl Univ, Res Sch Psychol, Bldg 39, Canberra, ACT 2600, Australia.
   [Dawel, Amy; Wong, Tsz Ying; McMorrow, Jodie; Ivanovici, Callin; Irons, Jessica; Lane, Jo; McKone, Elinor] Australian Natl Univ, Arc Ctr Excellence Cognit & Its Disorders, Canberra, ACT, Australia.
   [He, Xuming] ShanghaiTech Univ, Sch Informat Sci & Technol, Shanghai, Peoples R China.
   [Barnes, Nick] CSIRO, Data61, Canberra, ACT, Australia.
   [Barnes, Nick] Bion Vis Australia, Carlton, Vic, Australia.
   [Irons, Jessica] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA.
C3 Australian National University; Australian National University;
   ShanghaiTech University; Commonwealth Scientific & Industrial Research
   Organisation (CSIRO); University System of Ohio; Ohio State University
RP Dawel, A (通讯作者)，Australian Natl Univ, Res Sch Psychol, Bldg 39, Canberra, ACT 2600, Australia.
EM amy.dawel@anu.edu.au
RI Barnes, Nick/Y-2744-2018; Dawel, Amy/AAY-2083-2020
OI Barnes, Nick/0000-0002-9343-9535; Dawel, Amy/0000-0001-6668-3121;
   Goodhew, Stephanie/0000-0002-5066-8303; McKone,
   Elinor/0000-0003-1655-4297; Lane, Jo/0000-0002-2518-1050; Wong, Tsz
   Ying/0000-0003-1275-2202
FU Australian Research Council [DE140101734, DP150100684]; ARC Centre of
   Excellence in Cognition and Its Disorders [CE110001021]
FX Funded by the Australian Research Council Grant DP150100684 to Elinor
   McKone and the ARC Centre of Excellence in Cognition and Its Disorders
   (CE110001021) http://www.ccd.edu.au (funding Elinor McKone and Amy
   Dawel); Stephanie C. Goodhew supported by Australian Research Council
   fellowship DE140101734. We thank Bionic Vision Australia, a Strategic
   Research Initiative of the Australian Research Council.
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NR 71
TC 6
Z9 6
U1 1
U2 15
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 1076-898X
EI 1939-2192
J9 J EXP PSYCHOL-APPL
JI J. Exp. Psychol.-Appl.
PD JUN
PY 2019
VL 25
IS 2
BP 256
EP 279
DI 10.1037/xap0000180
PG 24
WC Psychology, Applied
WE Social Science Citation Index (SSCI)
SC Psychology
GA IB1BT
UT WOS:000469999100008
PM 30321022
DA 2022-11-30
ER

PT J
AU Garg, A
   Yang, J
   Lee, W
   Tsang, SH
AF Garg, Aakriti
   Yang, Jin
   Lee, Winston
   Tsang, Stephen H.
TI Stem Cell Therapies in Retinal Disorders
SO CELLS
LA English
DT Review
DE stem cells; gene therapy; retina; disease modeling
ID MACULAR DEGENERATION; PIGMENT EPITHELIUM; GENERATION; INDUCTION;
   DISEASE; RPE; HETEROGENEITY; PREVALENCE; MEMORY
AB Stem cell therapy has long been considered a promising mode of treatment for retinal conditions. While human embryonic stem cells (ESCs) have provided the precedent for regenerative medicine, the development of induced pluripotent stem cells (iPSCs) revolutionized this field. iPSCs allow for the development of many types of retinal cells, including those of the retinal pigment epithelium, photoreceptors, and ganglion cells, and can model polygenic diseases such as age-related macular degeneration. Cellular programming and reprogramming technology is especially useful in retinal diseases, as it allows for the study of living cells that have genetic variants that are specific to patients' diseases. Since iPSCs are a self-renewing resource, scientists can experiment with an unlimited number of pluripotent cells to perfect the process of targeted differentiation, transplantation, and more, for personalized medicine. Challenges in the use of stem cells are present from the scientific, ethical, and political realms. These include transplant complications leading to anatomically incorrect placement, concern for tumorigenesis, and incomplete targeting of differentiation leading to contamination by different types of cells. Despite these limitations, human ESCs and iPSCs specific to individual patients can revolutionize the study of retinal disease and may be effective therapies for conditions currently considered incurable.
C1 [Garg, Aakriti; Yang, Jin; Lee, Winston; Tsang, Stephen H.] Columbia Univ, Med Ctr, Edward S Harkness Eye Inst, Jonas Childrens Vis Care, 635 West 165th St,Box 112, New York, NY 10032 USA.
   [Garg, Aakriti; Yang, Jin; Lee, Winston; Tsang, Stephen H.] Columbia Univ, Med Ctr, Edward S Harkness Eye Inst, Bernard & Shirlee Brown Glaucoma Lab,Dept Ophthal, 635 West 165th St,Box 112, New York, NY 10032 USA.
   [Yang, Jin; Lee, Winston; Tsang, Stephen H.] Columbia Univ, Coll Phys & Surg, Dept Pathol & Cell Biol, New York, NY 10032 USA.
C3 Columbia University; Columbia University; Columbia University
RP Tsang, SH (通讯作者)，Columbia Univ, Med Ctr, Edward S Harkness Eye Inst, Jonas Childrens Vis Care, 635 West 165th St,Box 112, New York, NY 10032 USA.; Tsang, SH (通讯作者)，Columbia Univ, Med Ctr, Edward S Harkness Eye Inst, Bernard & Shirlee Brown Glaucoma Lab,Dept Ophthal, 635 West 165th St,Box 112, New York, NY 10032 USA.; Tsang, SH (通讯作者)，Columbia Univ, Coll Phys & Surg, Dept Pathol & Cell Biol, New York, NY 10032 USA.
EM ag2965@columbia.edu; yangjinchina324@gmail.com;
   wl2355@cumc.columbia.edu; sht2@columbia.edu
RI Lee, Winston/CAA-0102-2022
OI Garg Shukla, Aakriti/0000-0002-0765-8337; Lee,
   Winston/0000-0002-1777-8519
FU National Institute of Health [5P30EY019007, R01EY018213, R01EY024698,
   R01EY026682, R21AG050437]; National Cancer Institute Core
   [5P30CA013696]; Research to Prevent Blindness (RPB) Physician-Scientist
   Award; RPB, New York, NY, USA; Tistou and Charlotte Kerstan Foundation;
   Schneeweiss Stem Cell Fund, New York State [C029572]; Foundation
   Fighting Blindness New York Regional Research Center Grant
   [C-NY05-0705-0312]; Crowley Family Fund; Gebroe Family Foundation;
   NATIONAL CANCER INSTITUTE [P30CA013696] Funding Source: NIH RePORTER;
   NATIONAL EYE INSTITUTE [R01EY026682, P30EY019007, R01EY024698,
   R01EY018213] Funding Source: NIH RePORTER; NATIONAL INSTITUTE ON AGING
   [R21AG050437] Funding Source: NIH RePORTER
FX Jonas Children's Vision Care, and Bernard & Shirlee Brown Glaucoma
   Laboratory are supported by the 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. S.H.T. is a member of the RD-CURE Consortium and is
   supported by the Tistou and Charlotte Kerstan Foundation, the
   Schneeweiss Stem Cell Fund, New York State [C029572], the Foundation
   Fighting Blindness New York Regional Research Center Grant
   [C-NY05-0705-0312], the Crowley Family Fund, and the Gebroe Family
   Foundation.
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NR 43
TC 25
Z9 27
U1 0
U2 10
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2073-4409
J9 CELLS-BASEL
JI Cells
PD MAR
PY 2017
VL 6
IS 1
AR 4
DI 10.3390/cells6010004
PG 7
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA FR0XJ
UT WOS:000418787000003
PM 28157165
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Ranjbar, M
   Brinkmann, MP
   Tura, A
   Rudolf, M
   Miura, Y
   Grisanti, S
AF Ranjbar, Mahdy
   Brinkmann, Max Philipp
   Tura, Ayseguel
   Rudolf, Martin
   Miura, Yoko
   Grisanti, Salvatore
TI Ranibizumab interacts with the VEGF-A/VEGFR-2 signaling pathway in human
   RPE cells at different levels
SO CYTOKINE
LA English
DT Article
DE Ranibizumab; RPE; VEGF-A; VEGFR-2; Oxidative stress
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL-PIGMENT EPITHELIUM; AUTOCRINE
   SURVIVAL FACTOR; MACULAR DEGENERATION; OXIDATIVE STRESS; FACTOR VEGF;
   IN-VITRO; BEVACIZUMAB; EXPRESSION; ATROPHY
AB Vascular endothelial growth factor (VEGF) secreted by the retinal pigment epithelium (RPE) plays an important role in ocular homeostasis, but also in diseases, most notably age-related macular degeneration (AMD). To date, anti-VEGF drugs like ranibizumab have been shown to be most effective in treating these pathologic conditions. However, clinical trials suggest that the RPE could degenerate and perish through anti-VEGF treatment. Herein, we evaluated possible pathways and outcomes of the interaction between ranibizumab and human RPE cells (ARPE-19). Results indicate that ranibizumab affects the VEGF-A metabolism in RPE cells from an extra- as well as intracellular site. The drug is taken up into the cells, with the VEGF receptor 2 (VEGFR-2) being involved, and decreases VEGF-A protein levels within the cells as well as extracellularly. Oxidative stress plays a key role in various inflammatory disorders of the eye. Our results suggest that oxidative stress inhibits RPE cell proliferation. This anti-proliferative effect on RPE cells is significantly enhanced through ranibizumab, which does not inhibit RPE cell proliferation substantially in absence of relevant oxidative stress. Therefore, we emphasize that anti-VEGF treatment should be selected carefully in AMD patients with preexistent extensive RPE atrophy. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Ranjbar, Mahdy; Brinkmann, Max Philipp; Tura, Ayseguel; Rudolf, Martin; Miura, Yoko; Grisanti, Salvatore] Univ Lubeck, Dept Ophthalmol, Lubeck, Germany.
   [Ranjbar, Mahdy; Brinkmann, Max Philipp] Univ Lubeck, Lab Angiogenesis & Ocular Cell Transplant, Lubeck, Germany.
   [Miura, Yoko] Med Univ Lubeck, Inst Biomed Opt, Lubeck, Germany.
C3 University of Lubeck; University of Lubeck; University of Lubeck
RP Ranjbar, M (通讯作者)，Med Univ Lubeck, Lab Angiogenesis & Ocular Cell Transplantat, Dept Ophthalmol, Ratzeburger Allee 160, D-23538 Lubeck, Germany.
EM eye.research101@gmail.com; maxphilipp.brinkmann@uksh.de;
   ayseguel.tura@uksh.de; mirudolf@aol.com; miura@bmo.uni-luebeck.de;
   salvatore.grisanti@uksh.de
RI Brinkmann, Max/AAA-1171-2021; Miura, Yoko/B-5588-2015
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NR 45
TC 12
Z9 12
U1 0
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD JUL
PY 2016
VL 83
BP 210
EP 216
DI 10.1016/j.cyto.2016.04.014
PG 7
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA DN7AS
UT WOS:000377228300028
PM 27163716
DA 2022-11-30
ER

PT J
AU Zhao, T
   Zhang, J
   Zhang, YY
   Huang, JJ
   Wang, X
   Zhang, YQ
   Zhang, M
   Yuan, Y
   Xiao, K
   Li, HX
   Zhong, ZH
AF Zhao, Tao
   Zhang, Jie
   Zhang, Yanyan
   Huang, Jingjing
   Wang, Xin
   Zhang, Yingqian
   Zhang, Ming
   Yuan, Ye
   Xiao, Kai
   Li, Hongxia
   Zhong, Zhihui
TI Vascular Endothelial Growth Factor Receptor 2 Antibody, BC001,
   Attenuates Laser-Induced Choroidal Neovascularization in Rhesus Monkeys
   (Macaca mulatta)
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID MACULAR DEGENERATION; DENDRITIC CELLS; VEGF-B; RANIBIZUMAB; BEVACIZUMAB
AB Purpose: A study was conducted to evaluate the inhibitory effects of vascular endothelial growth factor receptor 2 (VEGFR2) monoclonal antibody, BC001, against laser-induced choroidal neovascularization (CNV). Methods: We induced the experimental CNV in rhesus monkey eyes using laser photocoagulation. Monkeys were randomly assigned to 4 groups that received a single intravitreal administration of BC001 at 0 (vehicle-treated group), 0.05, 0.2, and 0.5mg/eye. Fundus fluorescein angiography, optical coherence tomography, and histological studies were used for evaluations. The ocular recovery was determined by comparing changes of fluorescein leaking area and thickness of disrupted retina around the laser burn spot before and after drug administration. Choroidal blood vessels were stained and quantified by lectin staining. Hematoxylin and eosin staining was performed to determine the general histological complications. Results: An intravitreal injection of BC001 at 0.05, 0.2, and 0.5mg per eye at 20 days after laser burn significantly reduced the CNV-induced fluorescein leakage, retina pathology, and aberrant choroidal vessel growth and did not change intraocular pressure or induce any immune response. Conclusion: BC001 confers significant inhibitory effects against laser-induced CNV in rhesus monkeys, thereby suggesting that prevention of VEGFR2 activation may be promising as an alternative therapeutic target for exudative age-related macular degeneration.
C1 [Zhao, Tao; Yuan, Ye] Shandong Buchang Pharmaceut Co, Heze, Peoples R China.
   [Zhang, Jie; Wang, Xin; Zhang, Yingqian; Xiao, Kai; Li, Hongxia; Zhong, Zhihui] Sichuan Univ, West China Hosp, Lab Nonhuman Primate Dis Modeling Res, State Key Lab Biotherapy, Chengdu 610041, Peoples R China.
   [Zhang, Yanyan; Huang, Jingjing; Wang, Xin; Xiao, Kai; Zhong, Zhihui] Sichuan Kangcheng Biotech Co Inc, Chengdu, Peoples R China.
   [Zhang, Ming] Sichuan Univ, West China Hosp, Dept Ophthalmol, Chengdu 610041, Peoples R China.
C3 Sichuan University; Sichuan University
RP Zhong, ZH (通讯作者)，Sichuan Univ, West China Hosp, Lab Nonhuman Primate Dis Modeling Res, State Key Lab Biotherapy, 28 Gaopeng Ave, Chengdu 610041, Peoples R China.
EM zhihui.zhong@gmail.com
OI Zhang, Ming/0000-0003-0151-7813
FU National Program of High Technology Research and Development of China
   [2012AA020702]
FX The authors thank Chunyan Hu and her colleagues in the Department of
   Pathology of the National Chengdu Center for Safety Evaluation of Drugs
   for their warm-hearted help and support in histological studies. The
   development of the monkey CNV model was supported by the National
   Program of High Technology Research and Development of China
   (2012AA020702). Shandong Buchang Pharmaceutical Company provided full
   support to the efficacy evaluation study of BC001.
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NR 32
TC 5
Z9 6
U1 0
U2 9
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1080-7683
EI 1557-7732
J9 J OCUL PHARMACOL TH
JI J. Ocular Pharmacol. Ther.
PD DEC 1
PY 2015
VL 31
IS 10
BP 611
EP 616
DI 10.1089/jop.2014.0148
PG 6
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA CX4TZ
UT WOS:000365694500004
PM 26334588
DA 2022-11-30
ER

PT J
AU Miere, A
   Querques, G
   Semoun, O
   El Ameen, A
   Capuano, V
   Souied, EH
AF Miere, Alexandra
   Querques, Giuseppe
   Semoun, Oudy
   El Ameen, Ala'a
   Capuano, Vittorio
   Souied, Eric H.
TI OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN EARLY TYPE 3
   NEOVASCULARIZATION
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; Type 3 neovascularization;
   chorioretinal anastomosis; retinal angiomatous proliferation; optical
   coherence tomography angiography
ID RETINAL ANGIOMATOUS PROLIFERATION; CHOROIDAL NEOVASCULARIZATION; MACULAR
   DEGENERATION; OCT ANGIOGRAPHY; ANASTOMOSIS; SPECTRUM; THERAPY; LAYERS
AB Purpose: To report the imaging features of Type 3 neovascularization secondary to exudative age-related macular degeneration on optical coherence tomography angiography (OCTA).
   Methods: All consecutive treatment-naive patients diagnosed with early-stage Type 3 neovascularization underwent imaging by color retinal photographs or multicolor imaging, fluorescein angiography, indocyanine green angiography, spectral domain optical coherence tomography, and OCTA. The OCTA features were analyzed and correlated with the findings of conventional angiography and spectral domain optical coherence tomography.
   Results: A total of 18 treatment-naive eyes of 18 consecutive patients (13 females and 5 males; mean age 81.3 6.0) were included in the analysis. Optical coherence tomography angiography showed lesions characterized by a retinal-retinal anastomosis that emerged from the deep capillary plexus, forming in all 18 eyes a clear tuft-shaped high-flow network in the outer retinal segmentation, finally abutting in the subretinal pigment epithelium space. In 15 of 18 eyes, in the choriocapillaris segmentation, there appeared a small clew-like lesion, which in 2 cases seemed connected with the choroid through a small caliber vessel.
   Conclusion: Optical coherence tomography angiography of treatment-naive Type 3 neovascularization showed almost constantly a high-flow, tuft-shaped abnormal outer retinal proliferation, frequently associated to a small clew-like lesion in the choriocapillaris layer.
C1 [Miere, Alexandra; Querques, Giuseppe; Semoun, Oudy; El Ameen, Ala'a; Capuano, Vittorio; Souied, Eric H.] Univ Paris Est Creteil, Ctr Hosp Intercommunal Creteil, Dept Ophthalmol, F-94000 Creteil, France.
C3 Universite Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil
RP Querques, G (通讯作者)，Univ Paris Est Creteil, Ctr Hosp Intercommunal Creteil, Dept Ophthalmol, 40 Ave Verdun, F-94000 Creteil, France.
EM giuseppe.querques@hotmail.it
RI Miere, Alexandra/AIC-4074-2022
OI Miere, Alexandra/0000-0003-4123-8210; EL AMEEN,
   Ala'a/0000-0001-8013-3708; Querques, Giuseppe/0000-0002-3292-9581
CR Bressler Neil M, 2004, JAMA, V291, P1900, DOI 10.1001/jama.291.15.1900
   Dansingani KK, 2015, EYE, V29, P703, DOI 10.1038/eye.2015.27
   de Carlo TE, 2015, OPHTHALMOLOGY, V122, P1228, DOI 10.1016/j.ophtha.2015.01.029
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NR 23
TC 64
Z9 66
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD NOV
PY 2015
VL 35
IS 11
BP 2236
EP 2241
DI 10.1097/IAE.0000000000000834
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CV5LD
UT WOS:000364311100010
PM 26457399
DA 2022-11-30
ER

PT J
AU Kalf, RRJ
   Mihaescu, R
   Kundu, S
   de Knijff, P
   Green, RC
   Janssens, ACJW
AF Kalf, Rachel R. J.
   Mihaescu, Raluca
   Kundu, Suman
   de Knijff, Peter
   Green, Robert C.
   Janssens, A. Cecile J. W.
TI Variations in predicted risks in personal genome testing for common
   complex diseases
SO GENETICS IN MEDICINE
LA English
DT Article
DE direct-to-consumer; genetic testing; genomics; personal genome testing;
   risk prediction
ID PATHWAY; CURVE
AB Purpose: The promise of personalized genomics for common complex diseases depends, in part, on the ability to predict genetic risks on the basis of single nucleotide polymorphisms. We examined and compared the methods of three companies (23andMe, deCODEme, and Navigenics) that have offered direct-to-consumer personal genome testing.
   Methods: We simulated genotype data for 100,000 individuals on the basis of published genotype frequencies and predicted disease risks using the methods of the companies. Predictive ability for six diseases was assessed by the AUC.
   Results: AUC values differed among the diseases and among the companies. The highest values of the AUC were observed for age-related macular degeneration, celiac disease, and Crohn disease. The largest difference among the companies was found for celiac disease: the AUC was 0.73 for 23andMe and 0.82 for deCODEme. Predicted risks differed substantially among the companies as a result of differences in the sets of single nucleotide polymorphisms selected and the average population risks selected by the companies, and in the formulas used for the calculation of risks.
   Conclusion: Future efforts to design predictive models for the genomics of common complex diseases may benefit from understanding the strengths and limitations of the predictive algorithms designed by these early companies.
C1 [Kalf, Rachel R. J.; Mihaescu, Raluca; Kundu, Suman; Janssens, A. Cecile J. W.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
   [de Knijff, Peter] Leiden Univ, Med Ctr, Dept Human & Clin Genet, Leiden, Netherlands.
   [Green, Robert C.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
   [Green, Robert C.] Harvard Univ, Sch Med, Boston, MA USA.
   [Janssens, A. Cecile J. W.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA.
C3 Erasmus University Rotterdam; Erasmus MC; Leiden University; Leiden
   University Medical Center (LUMC); Leiden University - Excl LUMC; Harvard
   University; Brigham & Women's Hospital; Harvard University; Harvard
   Medical School; Emory University; Rollins School Public Health
RP Janssens, ACJW (通讯作者)，Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
EM cecile.janssens@emory.edu
RI Kundu, Suman/I-2603-2019; de Knijff, Peter/Y-2519-2018
OI Kundu, Suman/0000-0002-6305-2559; de Knijff, Peter/0000-0002-0899-771X;
   Kalf, Rachel/0000-0002-9029-4713; Janssens, A Cecile/0000-0002-6153-4976
FU Centre for Medical Systems Biology; Netherlands Organization for
   Scientific Research; NATIONAL HUMAN GENOME RESEARCH INSTITUTE
   [R01HG005092] Funding Source: NIH RePORTER
FX This work was supported by the Centre for Medical Systems Biology and
   the Vidi grant from the Netherlands Organization for Scientific
   Research.
CR Cook NR, 2007, CIRCULATION, V115, P928, DOI 10.1161/CIRCULATIONAHA.106.672402
   deCODEme, SNP SEL RISK CALC DE
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   Navigenics, SCI NAV SERV
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   The Personalized Medicine Coalition, PERS GEN IND STAND S
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   Visscher PM, 2012, AM J HUM GENET, V90, P7, DOI 10.1016/j.ajhg.2011.11.029
NR 22
TC 47
Z9 48
U1 0
U2 19
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
EI 1530-0366
J9 GENET MED
JI Genet. Med.
PD JAN
PY 2014
VL 16
IS 1
BP 85
EP 91
DI 10.1038/gim.2013.80
PG 7
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA 284GO
UT WOS:000329304300012
PM 23807614
OA Bronze, Green Accepted
DA 2022-11-30
ER

PT J
AU Wysokinski, D
   Blasiak, J
   Dorecka, M
   Kowalska, M
   Robaszkiewicz, J
   Pawlowska, E
   Szaflik, J
   Szaflik, JP
AF Wysokinski, Daniel
   Blasiak, Janusz
   Dorecka, Mariola
   Kowalska, Marta
   Robaszkiewicz, Jacek
   Pawlowska, Elzbieta
   Szaflik, Jerzy
   Szaflik, Jacek Pawel
TI Variability of the Transferrin Receptor 2 Gene in AMD
SO DISEASE MARKERS
LA English
DT Article
ID MACULAR DEGENERATION; OXIDATIVE STRESS; IRON; HEMOCHROMATOSIS; SEVERITY
AB Oxidative stress is a major factor in the pathogenesis of age-related macular degeneration (AMD). Iron may catalyze the Fenton reaction resulting in overproduction of reactive oxygen species. Transferrin receptor 2 plays a critical role in iron homeostasis and variability in its gene may influence oxidative stress and AMD occurrence. To verify this hypothesis we assessed the association between polymorphisms of the TFR2 gene and AMD. A total of 493AMDpatients and 171matched controls were genotyped for the two polymorphisms of the TFR2 gene: c.1892C>T (rs2075674) and c.-258+123T>C (rs4434553). We also assessed the modulation of someAMDrisk factors by these polymorphisms. TheCCand TT genotypes of the c.1892C>Twere associatedwithAMDoccurrence but the latter only in obese patients. The other polymorphism was not associated with AMD occurrence, but the CC genotype was correlated with an increasing AMD frequency in subjects with BMI < 26. The TT genotype and the T allele of this polymorphism decreased AMD occurrence in subjects above 72 years, whereas the TC genotype and the C allele increased occurrence of AMD in this group. The c.1892C>T and c.-258+123T>C polymorphisms of the TRF2 gene may be associated with AMD occurrence, either directly or by modulation of risk factors.
C1 [Wysokinski, Daniel; Blasiak, Janusz] Univ Lodz, Dept Mol Genet, PL-90236 Lodz, Poland.
   [Dorecka, Mariola] Med Univ Silesia, Dept Ophthalmol, PL-40514 Katowice, Poland.
   [Kowalska, Marta; Robaszkiewicz, Jacek] Laser Ctr Okulisty, PL-00621 Warsaw, Poland.
   [Kowalska, Marta] Med Univ Warsaw, Dept Ophthalmol, PL-02005 Warsaw, Poland.
   [Pawlowska, Elzbieta] Med Univ Lodz, Dept Dev Dent, PL-92216 Lodz, Poland.
   [Szaflik, Jerzy; Szaflik, Jacek Pawel] Med Univ Warsaw, Dept Ophthalmol, PL-03709 Warsaw, Poland.
   [Szaflik, Jerzy; Szaflik, Jacek Pawel] Samodzielny Publ Klin Szpital Okulisty, PL-03709 Warsaw, Poland.
C3 University of Lodz; Medical University Silesia; Medical University of
   Warsaw; Medical University Lodz; Medical University of Warsaw
RP Szaflik, JP (通讯作者)，Med Univ Warsaw, Dept Ophthalmol, Sierakowskiego 13, PL-03709 Warsaw, Poland.
EM szaflik@ophthalmology.pl
OI Pawlowska, Elzbieta/0000-0002-5373-4783; Blasiak,
   Janusz/0000-0001-9539-9584; Dorecka, Mariola/0000-0003-1768-9628;
   Szaflik, Jerzy/0000-0002-7601-1326
FU Polish Ministry of Science and Higher Education [N N402 248 336]
FX This work was supported by Grant N N402 248 336 from the Polish Ministry
   of Science and Higher Education.
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NR 31
TC 4
Z9 4
U1 0
U2 4
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 0278-0240
EI 1875-8630
J9 DIS MARKERS
JI Dis. Markers
PY 2014
VL 2014
AR 507356
DI 10.1155/2014/507356
PG 8
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental; Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine; Pathology
GA AA7UN
UT WOS:000331302500001
PM 24648608
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Hassanshahi, M
   Khabbazi, S
   Hassanshahi, AR
   Mohammadi, O
AF Hassanshahi, Mohammadhossein
   Khabbazi, Samira
   Hassanshahi, Ali Reza
   Mohammadi, Omid
TI Angiogenesis and current approaches to deal with its misregulation in
   related diseases
SO LIFE SCIENCE JOURNAL-ACTA ZHENGZHOU UNIVERSITY OVERSEAS EDITION
LA English
DT Article
DE Angiogenesis; pre-existing; anti-angiogenic; blood; misregulation
ID INHIBITS ANGIOGENESIS; MONOCLONAL-ANTIBODIES; TUMOR ANGIOGENESIS;
   ANTIANGIOGENIC THERAPY; VASCULAR-PERMEABILITY; ENDOTHELIAL-CELLS;
   CANCER; GROWTH; INTEGRINS; PEPTIDE
AB Angiogenesis, which is the formation of blood vessels from pre-existing vessels, normally supply nutrition and oxygen to cells and tissues. In medicine point of view, regulation of angiogenesis is disrupted in many diseases such as cancers, psoriasis, age related macular degeneration, diabetes, proliferative retinopathies and rheumatoid arthritis. How to suppress, control and regulate the angiogenesis have been very challenging tasks in order to provide better and more effective treatments for related patients. With this regard, anti-angiogenic therapy has been considered as a potential approach to do so. However, anti-angiogenic agents are not completely safe and present side effects. Therefore, many attentions have been paid to understand more about molecular and cellular mechanisms involved in angiogenesis in order to prevent many life-threating side effects of anti-angiogenic agents. It may lead to discovering more desirable drugs to tackle angiogenesis. This review aims to give an overview about what angiogenesis is as well as present the most important factors involved in angiogenesis. It also attempts to describe current approaches and challenges in controlling angiogenesis. [Mohammadhossein Hassanshahi, Samira Khabbazi, Ali Reza Hassanshahi, omid mohammadi. Angiogenesis and current approaches to deal with its misregulation in related diseases. Life Sci J 2012; 9(4): 4892-4902] (ISSN: 1097-8135). http://www.lifesciencesite.com. 735
EM Hassanshahi.hossein@gmail.com
RI Hassanshahi, Mohammadhossein/ABF-5123-2020; Hassanshahi,
   Gholamhossein/O-1552-2017; khabbazi, samira/B-9907-2014
OI Hassanshahi, Gholamhossein/0000-0002-4829-1586; Hassanshahi,
   Mohammadhossein/0000-0002-4097-8527
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NR 52
TC 0
Z9 0
U1 1
U2 3
PU MARSLAND PRESS
PI LANSING
PA PO BOX 21126, LANSING, MI 48909 USA
SN 1097-8135
J9 LIFE SCI J
JI Life Sci. J.
PY 2012
VL 9
IS 4
BP 4892
EP 4902
PG 11
WC Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Life Sciences & Biomedicine - Other Topics
GA 113RQ
UT WOS:000316686000112
DA 2022-11-30
ER

PT J
AU Riveiro-Alvarez, R
   Aguirre-Lamban, J
   Lopez-Martinez, MA
   Trujillo-Tiebas, MJ
   Cantalapiedra, D
   Vallespin, E
   Avila-Fernandez, A
   Ramos, C
   Ayuso, C
AF Riveiro-Alvarez, R.
   Aguirre-Lamban, J.
   Angel Lopez-Martinez, M.
   Jose Trujillo-Tiebas, M.
   Cantalapiedra, D.
   Vallespin, E.
   Avila-Fernandez, A.
   Ramos, C.
   Ayuso, C.
TI Frequency of ABCA4 mutations in 278 Spanish controls: an insight into
   the prevalence of autosomal recessive Stargardt disease
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID GENE ABCR; MACULAR DEGENERATION; RETINITIS-PIGMENTOSA; DYSTROPHY;
   RETINOPATHIES
AB Aim: To determine the carrier frequency of ABCA4 mutations in order to achieve an insight into the prevalence of autosomal recessive Stargardt disease (arSTGD) in the Spanish population.
   Methods: arSTGD patients (n = 133) were analysed using ABCR400 microarray and sequencing. Control subjects were analysed by two different strategies: 200 individuals were screened for the p. Arg1129Leu mutation by denaturing-HPLC and sequencing; 78 individuals were tested for variants with the microarray and sequencing.
   Results: For the first strategy in control subjects, the p. Arg1129Leu variant was found in two heterozygous individuals, which would mean a carrier frequency for any variant of similar to 6.0% and a calculated arSTGD prevalence of 1:1000. For the second strategy, carrier frequency was 6.4% and therefore an estimated prevalence of the disease of 1:870.
   Conclusion: Calculated prevalence of arSTGD based on the ABCA4 carrier frequency could be considerably higher than previous estimation. This discrepancy between observed (genotypic) and estimated (phenotypic) prevalence could be due to the existence of non-pathological or low penetrance alleles, which may result in late-onset arSTGD or may be implicated in age-related macular degeneration. This situation should be regarded with especial care when genetic counselling is given and further follow-up of these patients should be recommended.
C1 [Riveiro-Alvarez, R.; Aguirre-Lamban, J.; Angel Lopez-Martinez, M.; Jose Trujillo-Tiebas, M.; Cantalapiedra, D.; Vallespin, E.; Avila-Fernandez, A.; Ramos, C.; Ayuso, C.] Fdn Jimenez Diaz, Dept Genet, E-28040 Madrid, Spain.
   [Riveiro-Alvarez, R.; Aguirre-Lamban, J.; Angel Lopez-Martinez, M.; Jose Trujillo-Tiebas, M.; Cantalapiedra, D.; Vallespin, E.; Avila-Fernandez, A.; Ramos, C.; Ayuso, C.] ISCIII, CIBERER, Madrid, Spain.
C3 CIBER - Centro de Investigacion Biomedica en Red; CIBERER; Instituto de
   Salud Carlos III
RP Riveiro-Alvarez, R (通讯作者)，Fdn Jimenez Diaz, Dept Genet, Avd Reyes Catolicos 2, E-28040 Madrid, Spain.
EM rriveiro@fjd.es
RI Vallespin, Elena/E-5277-2018
OI Vallespin, Elena/0000-0002-8080-8629; Ayuso, Carmen/0000-0002-9242-7065
FU FIS (Health Research Fund) [06/0027]; Fundacion Mutua Madrilena
   [30171/005]; EviGenoRet [LSHG-CT-2005-512036]; CIBER-ER from the
   Instituto de Salud Carlos III [06/07/0036]
FX Supported by FIS (Health Research Fund) 06/0027, Fundacion Mutua
   Madrilena (30171/005) and EviGenoRet (LSHG-CT-2005-512036). R R-A's work
   is supported by CIBER-ER from the Instituto de Salud Carlos III
   (06/07/0036).
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NR 21
TC 33
Z9 36
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 OCT
PY 2009
VL 93
IS 10
BP 1359
EP 1364
DI 10.1136/bjo.2008.148155
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 498JN
UT WOS:000270135700019
PM 18977788
OA Green Published, Green Submitted, hybrid
DA 2022-11-30
ER

PT J
AU Murdaugh, LS
   Dillon, J
   Gaillard, ER
AF Murdaugh, L. S.
   Dillon, J.
   Gaillard, E. R.
TI Modifications to the basement membrane protein laminin using
   glycolaldehyde and A2E: A model for aging in Bruch's membrane
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE A2E; blue light damage; oxidative stress; Bruch's membrane; age-related
   macular degeneration; reactive aldehydes
ID RETINAL-PIGMENT EPITHELIUM; GLYCATION END-PRODUCTS; AGE-RELATED-CHANGES;
   MACULAR DEGENERATION; IV COLLAGEN; NONENZYMATIC GLYCOSYLATION;
   EXTRACELLULAR-MATRIX; SCAVENGER RECEPTOR; LIPOFUSCIN; CELLS
AB In a variety of retinal diseases, including age-related macular degeneration (AMD); basement membranes are susceptible to alterations in structure and function. Chemical modifications to basement membrane proteins may deleteriously affect Bruch's membrane leading to the development of AMD. The purpose of this study was to investigate modifications from glycolaldehyde and A2E, which are present in the retinal pigment epithelium (RPE), on the membrane like protein fragment, laminin, as a model for aging of Bruch's membrane in age related eye diseases. Laminin was allowed to react with either glycolaldehyde or A2E during irradiation of A2E and then tryptically digested before analysis with electrospray ionization mass spectrometry (ESI-MS). Modifications to laminin occurred preferentially on lysine or arginine residues. The A2E modified laminin fragments are consistent with additions of A2E derived aldehydes resulting from cleavages closest to the pyridinium ring in A2E and oxidized A2E. These results provide evidence that A2E and advanced glycation endproducts (AGE) may be involved in modifications to essential basement membrane proteins leading to deleterious changes in the retinal pigment epithelium extracellular matrix (RPE-ECM) environment. These preliminary experiments are essential for the identification of these modifications in vivo. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Murdaugh, L. S.; Gaillard, E. R.] No Illinois Univ, Dept Chem & Biochem, De Kalb, IL 60115 USA.
   [Gaillard, E. R.] No Illinois Univ, Dept Biol Sci, De Kalb, IL 60115 USA.
   [Dillon, J.; Gaillard, E. R.] Columbia Univ, Coll Phys & Surg, Dept Ophthalmol, New York, NY USA.
C3 Northern Illinois University; Northern Illinois University; Columbia
   University
RP Gaillard, ER (通讯作者)，No Illinois Univ, Dept Chem & Biochem, De Kalb, IL 60115 USA.
EM gaillard@niu.edu
RI Gaillard, Elizabeth/M-2627-2019
FU Research to Prevent Blindness
FX The authors would like to thank Research to Prevent Blindness for
   generous support UPD).
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NR 51
TC 9
Z9 9
U1 0
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD AUG
PY 2009
VL 89
IS 2
BP 187
EP 192
DI 10.1016/j.exer.2009.03.021
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 480BQ
UT WOS:000268707200010
PM 19358843
DA 2022-11-30
ER

PT J
AU Stieger, K
   Mendes-Madeira, A
   Meur, GL
   Weber, M
   Deschamps, JY
   Nivard, D
   Provost, N
   Moullier, P
   Rolling, F
AF Stieger, K.
   Mendes-Madeira, A.
   Meur, G. L.
   Weber, M.
   Deschamps, J. -Y
   Nivard, D.
   Provost, N.
   Moullier, P.
   Rolling, F.
TI Oral administration of doxycycline allows tight control of transgene
   expression: a key step towards gene therapy of retinal diseases
SO GENE THERAPY
LA English
DT Article
DE doxycycline-regulated transgene expression; retina; nonhuman primate;
   AAV vectors; Epo; oral administration
ID CILIARY NEUROTROPHIC FACTOR; EPITHELIUM-DERIVED FACTOR; PIGMENTED
   EPITHELIUM; MEDIATED DELIVERY; NONHUMAN-PRIMATES; ANIMAL-MODELS;
   NEOVASCULARIZATION; DEGENERATION; INHIBITION; INJECTION
AB Gene transfer of neurotrophic or antiangiogenic factors has been shown to improve photoreceptor survival in retinal degenerative disorders (that is retinitis pigmentosa) and to prevent neovascularization in retinal vascular diseases (that is age-related macular degeneration, diabetic retinopathy). Expression of such neurotrophic or antiangiogenic factors after gene transfer requires the use of a regulatory system to control transgene expression to avoid unwanted side effects in cases of overexpression. In a previous study, we demonstrated that rAAV-mediated gene transfer of the tetracycline-regulatable (tetR) system allows transgene regulation in the retina of nonhuman primates after intravenous administration of doxycycline (Dox). The purpose of this study was to evaluate oral administration of Dox to control transgene expression in the retina, since the pharmacokinetics after oral administration of the inducer drug represent a key factor when considering advancing to clinical trials. We report on the outcome of this evaluation and demonstrate that oral administration of Dox at a dose that is clinically used in humans (5 mg kg(1) per day) is capable to continuously induce transgene expression in all macaques tested for 6 months. Moreover, control of transgene expression persists up to 4 years post-subretinal injection, with maximal induced levels of transgene product remaining stable over time.
C1 CHU Nantes, Hotel Dieu, INSERM, U649,UMR,Lab Therapie Genique, F-44035 Nantes 01, France.
   Estab Francais Sang, Nantes, France.
   CHU Nantes, Hotel Dieu, Serv Ophtalmol, F-44035 Nantes 01, France.
   Ecole Natl Vet Nantes, Serv Urgences, Nantes, France.
   Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL USA.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm);
   Nantes Universite; CHU de Nantes; Nantes Universite; CHU de Nantes;
   Ecole Nationale Veterinaire, Agroalimentaire et de l'Alimentation
   Nantes-Atlantique; State University System of Florida; University of
   Florida
RP Rolling, F (通讯作者)，CHU Nantes, Hotel Dieu, INSERM, U649,UMR,Lab Therapie Genique, Bat J Monnet,30 Ave J Monnet, F-44035 Nantes 01, France.
EM fabienne.rolling@univ-nantes.fr
RI Stieger, Knut/A-1600-2012
OI Stieger, Knut/0000-0002-8298-5629
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NR 36
TC 27
Z9 30
U1 0
U2 4
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 0969-7128
EI 1476-5462
J9 GENE THER
JI Gene Ther.
PD DEC
PY 2007
VL 14
IS 23
BP 1668
EP 1673
DI 10.1038/sj.gt.3303034
PG 6
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 235RM
UT WOS:000251252000008
PM 17914405
DA 2022-11-30
ER

PT J
AU Pickering, MC
   de Jorge, EG
   Martinez-Barricarte, R
   Recalde, S
   Garcia-Layana, A
   Rose, KL
   Moss, J
   Walport, MJ
   Cook, HT
   de Cordoba, SR
   Botto, M
AF Pickering, Matthew C.
   de Jorge, Elena Goicoechea
   Martinez-Barricarte, Ruben
   Recalde, Sergio
   Garcia-Layana, Alfredo
   Rose, Kirsten L.
   Moss, Jill
   Walport, Mark J.
   Cook, H. Terence
   de Cordoba, Santiago Rodriguez
   Botto, Marina
TI Spontaneous hemolytic uremic syndrome triggered by complement factor H
   lacking surface recognition domains
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; LIVER-TRANSPLANTATION;
   RENAL-TRANSPLANTATION; MACULAR DEGENERATION; DEPOSIT DISEASE; MUTATIONS;
   GENE; DEFICIENCY; ACTIVATION; REVEALS
AB Factor H (FH) is an abundant serum glycoprotein that regulates the alternative pathway of complement-preventing uncontrolled plasma C3 activation and nonspecific damage to host tissues. Age-related macular degeneration (AMD), atypical hemolytic uremic syndrome (aHUS), and membranoproliferative glomerulonephritis type II (MPGN2) are associated with polymorphisms or mutations in the FH gene (Cf h), suggesting the existence of a genotype phenotype relationship. Although AMD and MPGN2 share pathological similarities with the accumulation of complement-containing debris within the eye and kidney, respectively, aHUS is characterized by renal endothelial injury. This pathological distinction was reflected in our Cf h association analysis, which demonstrated that although AMD and MPGN2 share a Cf h at-risk haplotype, the haplotype for aHUS was unique. FH-deficient mice have uncontrolled plasma C3 activation and spontaneously develop MPGN2 but not aHUS. We show that these mice, transgenically expressing a mouse FH protein functionally equivalent to aHUS-associated human FH mutants, regulate C3 activation in plasma and spontaneously develop aHUS but not MPGN2. These animals represent the first model of aHUS and provide in vivo evidence that effective plasma C3 regulation and the defective control of complement activation on renal endothelium are the critical events in the molecular pathogenesis of FH-associated aHUS.
C1 Univ London Imperial Coll Sci & Technol, Fac Med, Dept Histopathol, Mol Genet & Rheumatol Sect, London W12 0NN, England.
   Ctr Invest Biol, Consejo Super Invest Cientif, Ctr Invest Biomed Red Enfermedades Raras, Inst Salud Carlos III,Dept Fisiopatol Celular Mol, Madrid 28040, Spain.
   Univ Navarra Clin, Dept Ophthalmol, Pamplona, Spain.
C3 Imperial College London; CIBER - Centro de Investigacion Biomedica en
   Red; CIBERER; Consejo Superior de Investigaciones Cientificas (CSIC);
   CSIC - Centro de Investigaciones Biologicas (CIB); Instituto de Salud
   Carlos III; University of Navarra
RP Pickering, MC (通讯作者)，Univ London Imperial Coll Sci & Technol, Fac Med, Dept Histopathol, Mol Genet & Rheumatol Sect, London W12 0NN, England.
EM matthew.pickering@imperial.ac.uk; SRdeCordoba@cib.csic.es
RI de Cordoba, Santiago Rodriguez/K-6727-2014; Mohammed, Imran/J-8271-2012;
   de Jorge, Elena Goicoechea/L-4580-2016; Recalde, Sergio/D-1815-2017;
   Barricarte, Ruben Martinez/W-8695-2019
OI de Cordoba, Santiago Rodriguez/0000-0001-6401-1874; Mohammed,
   Imran/0000-0002-8412-0768; de Jorge, Elena
   Goicoechea/0000-0002-4978-2483; Recalde, Sergio/0000-0002-9328-9725;
   Barricarte, Ruben Martinez/0000-0001-7925-449X; Walport,
   Mark/0000-0001-7220-5273; Pickering, Matthew/0000-0002-1153-0192
FU Wellcome Trust Funding Source: Medline
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NR 35
TC 201
Z9 223
U1 1
U2 9
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0022-1007
EI 1540-9538
J9 J EXP MED
JI J. Exp. Med.
PD JUN 11
PY 2007
VL 204
IS 6
BP 1249
EP 1256
DI 10.1084/jem.20070301
PG 8
WC Immunology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology; Research & Experimental Medicine
GA 177MX
UT WOS:000247158300003
PM 17517971
OA Green Submitted, Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Lu, JT
   Lee, CJ
   Bent, SF
   Fishman, HA
   Sabelman, EE
AF Lu, James T.
   Lee, Christina J.
   Bent, Stacey F.
   Fishman, Harvey A.
   Sabelman, Eric E.
TI Thin collagen film scaffolds for retinal epithelial cell culture
SO BIOMATERIALS
LA English
DT Article
DE retina; collagen; epithelial cell; cell viability
ID ANTERIOR LENS CAPSULE; PHYSICAL CROSS-LINKING; PIGMENT-EPITHELIUM;
   MACULAR DEGENERATION; AGE; TRANSPLANTATION; MEMBRANE; SUPPORT;
   PERMEABILITY; REATTACHMENT
AB Collagen films have been used in biological implantation and surgical grafts. The development of thin collagen films on the order of 10 mu m thick that ensure a planar distribution of implanted cells is a necessary step towards surgical grafts for treatment of age-related macular degeneration (AMD). Here, collagen films were manufactured on a Teflon support to a thickness of 2.4 +/- 0.2 mu m, comparable to that of native Bruch's membrane. Because one important function of Bruch's membrane is allowing the flow of nutrients and waste to and from the retinal pigment epithelium the diffusion properties of the collagen films were studied using blind-well chambers. The diffusion coefficient of the collagen film was determined to be 4.1 x 10(-10) cm(2)/s for 71,200 Da dextran molecules. Viability studies utilizing the blind-well chambers also confirmed that nutrient transport through the films was sufficient to sustain retinal pigment epithelial (RPE) cells. The films were bioassayed in a RPE cell culture model to confirm cell attachment and viability. RPE cells were shown to form an epithelial phenotype and were able to phagocytize photoreceptor outer segments. (c) 2006 Elsevier Ltd. All rights reserved.
C1 Stanford Univ, Dept Chem Engn, Stanford, CA 94305 USA.
   Plager Vis Ctr, Santa Cruz, CA 95065 USA.
   VA Palo Alto Hlth Care Syst, Rehabil R&D Ctr, Palo Alto, CA 94304 USA.
C3 Stanford University; US Department of Veterans Affairs; Veterans Health
   Administration (VHA); VA Palo Alto Health Care System
RP Lu, JT (通讯作者)，Stanford Univ, Dept Chem Engn, Stanford, CA 94305 USA.
EM jameslu@gmail.com
OI Bent, Stacey/0000-0002-1084-5336
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NR 36
TC 81
Z9 88
U1 0
U2 26
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 MAR
PY 2007
VL 28
IS 8
BP 1486
EP 1494
DI 10.1016/j.biomaterials.2006.11.023
PG 9
WC Engineering, Biomedical; Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Materials Science
GA 135BY
UT WOS:000244130000004
PM 17161864
DA 2022-11-30
ER

PT J
AU Ozawa, R
   Azuma, K
   Nomura, Y
   Murata, H
   Asaoka, R
   Kitamoto, K
   Ueda, K
   Inoue, T
   Obata, R
AF Ozawa, Rion
   Azuma, Keiko
   Nomura, Yoko
   Murata, Hiroshi
   Asaoka, Ryo
   Kitamoto, Kohdai
   Ueda, Kohei
   Inoue, Tatsuya
   Obata, Ryo
TI Association between retinal sensitivity and the presence of quiescent
   choroidal neovascularization in pachychoroid diseases
SO PLOS ONE
LA English
DT Article
ID CENTRAL SEROUS CHORIORETINOPATHY; OPTICAL COHERENCE TOMOGRAPHY;
   NONEXUDATIVE MACULAR NEOVASCULARIZATION; ANGIOGRAPHY; EYES;
   DEGENERATION; PREVALENCE
AB This study was conducted to examine retinal sensitivity (RS) in eyes with pachychoroid diseases and to analyze its association with the presence or absence of quiescent choroidal neovascularization (CNV), that can be protective against retinal dysfunction or atrophy in other macular diseases such as age-related macular degeneration. A total of 12 eyes of 12 patients aged >= 45 years having the characteristic findings of central serous chorioretinopathy but not presenting any exudative changes were included in this study. Choroidal vascular hyper permeability (CVH) was identified by indocyanine green angiography, and the presence or absence of CNV was evaluated by optical coherence tomography angiography. RS at 68 points was examined by microperimetry. The average RS corresponding to within and outside CVH was compared. The association between the difference in RS and the presence or absence of CNV was also analyzed. CNV was detected in six eyes (50%). In eyes without CNV, the RS within CVH was similar compared with that outside CVH. However, in eyes with CNV, the RS within CVH was significantly decreased compared with that outside CVH. Multiple regression analysis revealed the presence of CNV as an independent factor associated with RS. In eyes with pachychoroid diseases, RS decreased within the CVH area under the coexistence of nonexudative CNV.
C1 [Ozawa, Rion; Azuma, Keiko; Nomura, Yoko; Murata, Hiroshi; Kitamoto, Kohdai; Ueda, Kohei; Obata, Ryo] Univ Tokyo, Fac Med, Grad Sch Med, Dept Ophthalmol, Tokyo, Japan.
   [Asaoka, Ryo] Seirei Christopher Univ, Seirei Hamamatsu Gen Hosp, Dept Ophthalmol, Shizuoka, Japan.
   [Inoue, Tatsuya] Yokohama City Univ, Dept Ophthalmol & Microtechnol, Sch Med, Minami-ku, Yokohama, Kanagawa, Japan.
C3 University of Tokyo; Yokohama City University
RP Obata, R (通讯作者)，Univ Tokyo, Fac Med, Grad Sch Med, Dept Ophthalmol, Tokyo, Japan.
EM robatatky@g.ecc.u-tokyo.ac.jp
FU Japan Society for The Promotion of Science;  [21K16893]
FX Declarations Ethics approval and consent to participate. The study was
   conducted in accordance with the tenets of the Declaration of Helsinki
   and with the approval of the ethics committee at the coordinating center
   of the University of Tokyo. All patients provided written informed
   consent prior to participation in the study.
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NR 26
TC 0
Z9 0
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 26
PY 2022
VL 17
IS 7
DI 10.1371/journal.pone.0271543
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 4X1CI
UT WOS:000860587700025
PM 35881636
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Wei, Y
   Hsu, JC
   Chen, W
   Chew, EY
   Ding, Y
AF Wei, Yue
   Hsu, Jason C.
   Chen, Wei
   Chew, Emily Y.
   Ding, Ying
TI Identification and inference for subgroups with differential treatment
   efficacy from randomized controlled trials with survival outcomes
   through multiple testing
SO STATISTICS IN MEDICINE
LA English
DT Article
DE AMD progression; CE4; cross-talk plot; multiple testing; ratio of
   quantile survival; subgroup identification
ID MACULAR DEGENERATION; AREDS SUPPLEMENTS; CLINICAL-TRIAL; EYE DISEASE;
   PROGRESSION; ZINC; ASSOCIATION; REGRESSION; ANTIOXIDANT; CONFIDENT
AB With the uptake of targeted therapies, instead of the "one-fits-all" approach, modern randomized controlled trials (RCTs) often aim to develop treatments that target a subgroup of patients. Motivated by analyzing the Age-Related Eye Disease Study (AREDS) data, a large RCT to study the efficacy of nutritional supplements in delaying the progression of an eye disease, age-related macular degeneration (AMD), we develop a simultaneous inference procedure to identify and infer subgroups with differential treatment efficacy in RCTs with time-to-event outcomes. Specifically, we formulate the multiple testing problem through contrasts and construct their simultaneous confidence intervals, which appropriately control both within- and across-marker multiplicity. Realistic simulations are conducted using real genotype data to evaluate the method performance under various scenarios. The method is then applied to AREDS to assess the efficacy of antioxidants and zinc combination in delaying AMD progression. Multiple gene regions including ESRRB-VASH1 on chromosome 14 have been identified with subgroups showing differential efficacy. We further validate our findings in an independent subsequent RCT, AREDS2, by discovering consistent differential treatment responses in the targeted and non-targeted subgroups identified from AREDS. This multiple-testing-based simultaneous inference approach provides a step forward to confidently identify and infer subgroups in modern drug development.
C1 [Wei, Yue; Ding, Ying] Univ Pittsburgh, Dept Biostat, 130 De Soto St, Pittsburgh, PA 15261 USA.
   [Hsu, Jason C.] Ohio State Univ, Dept Stat, Columbus, OH 43210 USA.
   [Chen, Wei] Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15261 USA.
   [Chew, Emily Y.] NEI, NIH, Bethesda, MD 20892 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); University
   of Pittsburgh; University System of Ohio; Ohio State University;
   Pennsylvania Commonwealth System of Higher Education (PCSHE); University
   of Pittsburgh; National Institutes of Health (NIH) - USA; NIH National
   Eye Institute (NEI)
RP Ding, Y (通讯作者)，Univ Pittsburgh, Dept Biostat, 130 De Soto St, Pittsburgh, PA 15261 USA.
EM yingding@pitt.edu
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NR 50
TC 0
Z9 0
U1 0
U2 1
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD DEC 20
PY 2021
VL 40
IS 29
BP 6523
EP 6540
DI 10.1002/sim.9196
EA SEP 2021
PG 18
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 WX8YX
UT WOS:000697917800001
PM 34542190
DA 2022-11-30
ER

PT J
AU Khan, AH
   Sutton, J
   Cree, AJ
   Khandhadia, S
   De Salvo, G
   Tobin, J
   Prakash, P
   Arora, R
   Amoaku, W
   Issa, PC
   MacLaren, RE
   Bishop, PN
   Peto, T
   Mohamed, Q
   Steel, DH
   Sivaprasad, S
   Bailey, C
   Menon, G
   Kavanagh, D
   Lotery, AJ
AF Khan, Adnan H.
   Sutton, Janice
   Cree, Angela J.
   Khandhadia, Samir
   De Salvo, Gabriella
   Tobin, John
   Prakash, Priya
   Arora, Rashi
   Amoaku, Winfried
   Charbel Issa, Peter
   MacLaren, Robert E.
   Bishop, Paul N.
   Peto, Tunde
   Mohamed, Quresh
   Steel, David H.
   Sivaprasad, Sobha
   Bailey, Clare
   Menon, Geeta
   Kavanagh, David
   Lotery, Andrew J.
TI Prevalence and phenotype associations of complement factor I mutations
   in geographic atrophy
SO HUMAN MUTATION
LA English
DT Article
DE age-related macular degeneration; complement factor I; factor I;
   geographic atrophy; reticular pseudodrusen
ID RARE GENETIC-VARIANTS; SUBRETINAL DRUSENOID DEPOSITS; HEMOLYTIC-UREMIC
   SYNDROME; MACULAR DEGENERATION; RETICULAR PSEUDODRUSEN; FACTOR-H;
   HIGH-RISK; CFI GENE; DEFICIENCY; SUSCEPTIBILITY
AB Rare variants in the complement factor I (CFI) gene, associated with low serum factor I (FI) levels, are strong risk factors for developing the advanced stages of age-related macular degeneration (AMD). No studies have been undertaken on the prevalence of disease-causing CFI mutations in patients with geographic atrophy (GA) secondary to AMD. A multicenter, cross-sectional, noninterventional study was undertaken to identify the prevalence of pathogenic rare CFI gene variants in an unselected cohort of patients with GA and low FI levels. A genotype-phenotype study was performed. Four hundred and sixty-eight patients with GA secondary to AMD were recruited to the study, and 19.4% (n = 91) demonstrated a low serum FI concentration (below 15.6 mu g/ml). CFI gene sequencing on these patients resulted in the detection of rare CFI variants in 4.7% (n = 22) of recruited patients. The prevalence of CFI variants in patients with low serum FI levels and GA was 25%. Of the total patients recruited, 3.2% (n = 15) expressed a CFI variant classified as pathogenic or likely pathogenic. The presence of reticular pseudodrusen was detected in all patients with pathogenic CFI gene variants. Patients with pathogenic CFI gene variants and low serum FI levels might be suitable for FI supplementation in therapeutic trials.
C1 [Khan, Adnan H.; Sutton, Janice; Cree, Angela J.; Lotery, Andrew J.] Univ Southampton, Fac Med, Div Clin Neurosci Clin & Expt Sci, Southampton, Hants, England.
   [Khan, Adnan H.; Khandhadia, Samir; De Salvo, Gabriella; Lotery, Andrew J.] Univ Hosp Southampton NHS Fdn Trust, Southampton Eye Unit, Southampton, Hants, England.
   [Tobin, John] Gyroscope Therapeut Ltd, Stevenage, Herts, England.
   [Prakash, Priya] Princess Alexandra Hosp NHS Trust, Eye Unit, Harlow, Essex, England.
   [Arora, Rashi] Salisbury Dist Hosp, Salisbury NHS Fdn Trust, Dept Ophthalmol, Salisbury, Wilts, England.
   [Amoaku, Winfried] Nottingham Univ Hosp NHS Trust, Queens Med Ctr, Eye & ENT Ctr, Nottingham, England.
   [Charbel Issa, Peter; MacLaren, Robert E.] Oxford Univ Hosp NHS Fdn Trust, Oxford Eye Hosp, Oxford, England.
   [Charbel Issa, Peter; MacLaren, Robert E.] Oxford Univ Hosp NHS Fdn Trust, John Radcliffe Hosp, Oxford NIHR Biomed Res Ctr, Oxford, England.
   [Charbel Issa, Peter; MacLaren, Robert E.] Univ Oxford, Nuffield Dept Clin Neurosci, Nuffield Lab Ophthalmol, Oxford, England.
   [Bishop, Paul N.] Univ Manchester, Sch Biol Sci, Fac Med & Hlth, Div Evolut & Genom Sci, Manchester, Lancs, England.
   [Bishop, Paul N.] Manchester Univ NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester Royal Eye Hosp, Manchester, Lancs, England.
   [Peto, Tunde] Queens Univ Belfast, Inst Clin Sci, Sch Med, Ctr Publ Hlth, Belfast, Antrim, North Ireland.
   [Mohamed, Quresh] Gloucestershire Hosp NHS Fdn Trust, Gloucestershire Royal Hosp, Dept Ophthalmol, Gloucester, England.
   [Steel, David H.] South Tyneside & Sunderland NHS Fdn Trust, Sunderland Eye Infirm, Sunderland, England.
   [Steel, David H.] Newcastle Univ, Biosci Inst, Newcastle Upon Tyne, Tyne & Wear, England.
   [Sivaprasad, Sobha] UCL, Inst Ophthalmol, London, England.
   [Bailey, Clare] Univ Hosp Bristol NHS Fdn Trust, Bristol Eye Hosp, Clin Res Unit, Bristol, Avon, England.
   [Menon, Geeta] Frimley Hlth NHS Fdn Trust, Frimley Pk Hosp, Dept Ophthalmol, Camberley, England.
   [Kavanagh, David] Royal Victoria Infirm, Natl Renal Complement Therapeut Ctr, Newcastle Upon Tyne, Tyne & Wear, England.
   [Kavanagh, David] Newcastle Univ, Translat & Clin Res Inst, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
C3 University of Southampton; University of Southampton; University
   Hospital Southampton NHS Foundation Trust; Princess Alexandra Hospital
   NHS Trust; Salisbury District Hospital; Nottingham University Hospital
   NHS Trust; University of Nottingham; Oxford University Hospitals NHS
   Foundation Trust; Oxford University Hospitals NHS Foundation Trust;
   University of Oxford; University of Oxford; University of Manchester;
   Manchester Royal Eye Hospital; University of Manchester; Queens
   University Belfast; Gloucestershire Hospitals NHS Foundation Trust;
   Gloucestershire Royal Hospital; Newcastle University - UK; University of
   London; University College London; Bristol Eye Hospital; University of
   Bristol; Newcastle University - UK; Newcastle University - UK
RP Kavanagh, D (通讯作者)，Newcastle Univ, Translat & Clin Res Inst, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.; Lotery, AJ (通讯作者)，Univ Southampton, Fac Med, Clin & Expt Sci, Southampton SO17 1BJ, Hants, England.
EM david.kavanagh@newcastle.ac.uk; A.J.Lotery@soton.ac.uk
RI Khan, Adnan/CAH-3285-2022; Charbel Issa, Peter/E-8935-2018
OI Khan, Adnan/0000-0001-8153-8002; Sivaprasad, Sobha/0000-0001-8952-0659;
   Lotery, Andrew/0000-0001-5541-4305; DE SALVO,
   Gabriella/0000-0002-1185-6942; Amoaku, Winfried/0000-0001-5028-7984;
   Charbel Issa, Peter/0000-0002-0351-6673; Cree,
   Angela/0000-0002-1987-8900
FU Gyroscope Therapeutics Limited
FX Gyroscope Therapeutics Limited
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NR 62
TC 3
Z9 3
U1 1
U2 2
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 SEP
PY 2021
VL 42
IS 9
BP 1139
EP 1152
DI 10.1002/humu.24242
EA JUN 2021
PG 14
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA UD2DF
UT WOS:000667725000001
PM 34153144
OA Green Submitted, hybrid, Green Accepted, Green Published
DA 2022-11-30
ER

PT J
AU Pescina, S
   Sonvico, F
   Clementino, A
   Padula, C
   Santi, P
   Nicoli, S
AF Pescina, Silvia
   Sonvico, Fabio
   Clementino, Adryana
   Padula, Cristina
   Santi, Patrizia
   Nicoli, Sara
TI Preliminary Investigation on Simvastatin-Loaded Polymeric Micelles in
   View of the Treatment of the Back of the Eye
SO PHARMACEUTICS
LA English
DT Article
DE statins; simvastatin; ocular delivery; TPGS; polymeric micelles;
   trans-scleral; conjunctiva; ex vivo
ID OCULAR DRUG-DELIVERY; STATINS; MELANIN; CARRIERS; BINDING; NANOCARRIERS;
   ATORVASTATIN; ASSOCIATION; PROTEINS; DEPOSITS
AB There is increasing consensus in considering statins beneficial for age-related macular degeneration and in general, for immune and inflammatory mediated diseases affecting the posterior segment of the eye. However, all available data relate to oral administration, and safety and effectiveness of statins directly administered to the eye are not yet known, despite their ophthalmic administration could be beneficial. The aim was the development and the characterization of polymeric micelles based on TPGS or TPGS/poloxamer 407 to increase simvastatin solubility and stability and to enhance the delivery of the drug to the posterior segment of the eye via trans-scleral permeation. Simvastatin was chosen as a model statin and its active hydroxy acid metabolite was investigated as well. Results demonstrated that polymeric micelles increased simvastatin solubility at least 30-fold and particularly TPGS/poloxamer 407 mixed micelles, successfully stabilized simvastatin over time, preventing the hydrolysis when stored for 1 month at 4 degrees C. Furthermore, both TPGS (1.3 mPas) and mixed micelles (33.2 mPas) showed low viscosity, suitable for periocular administration. TPGS micelles resulted the best performing in delivery simvastatin either across conjunctiva or sclera in ex vivo porcine models. The data pave the way for a future viable ocular administration of statins.
C1 [Pescina, Silvia; Sonvico, Fabio; Clementino, Adryana; Padula, Cristina; Santi, Patrizia; Nicoli, Sara] Univ Parma, Dept Food & Drug, Parco Area Sci 27-A, I-43124 Parma, Italy.
C3 University of Parma
RP Pescina, S (通讯作者)，Univ Parma, Dept Food & Drug, Parco Area Sci 27-A, I-43124 Parma, Italy.
EM silvia.pescina@unipr.it; fabio.sonvico@unipr.it;
   adryana.rochaclementino@studenti.unipr.it; cristina.padula@unipr.it;
   patrizia.santi@unipr.it; sara.nicoli@unipr.it
RI Padula, Cristina/K-6372-2017; Sonvico, Fabio/G-7294-2012; Nicoli,
   Sara/J-5199-2012; Santi, Patrizia/G-8601-2011
OI Sonvico, Fabio/0000-0001-7372-1456; Nicoli, Sara/0000-0001-6955-0957;
   PESCINA, SILVIA/0000-0002-6131-4375; Santi, Patrizia/0000-0001-7601-7894
FU University of Parma
FX This work has been partially funded by grant from the University of
   Parma (FIL 2019-Fondi di Ateneo per la ricerca locale-to S.P.).
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NR 62
TC 1
Z9 1
U1 4
U2 10
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1999-4923
J9 PHARMACEUTICS
JI Pharmaceutics
PD JUN
PY 2021
VL 13
IS 6
AR 855
DI 10.3390/pharmaceutics13060855
PG 15
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA SY7GM
UT WOS:000666051800001
PM 34207544
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Delmas, D
   Cornebise, C
   Courtaut, F
   Xiao, JB
   Aires, V
AF Delmas, Dominique
   Cornebise, Clarisse
   Courtaut, Flavie
   Xiao, Jianbo
   Aires, Virginie
TI New Highlights of Resveratrol: A Review of Properties against Ocular
   Diseases
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Review
DE resveratrol; polyphenols; nutraceutical; ocular diseases; eyes; AMD;
   angiogenesis; diabetic retinopathy; cataract
ID PIGMENT EPITHELIAL-CELLS; ENDOTHELIAL GROWTH-FACTOR; CHEMOPREVENTIVE
   AGENT RESVERATROL; ACTIVATED PROTEIN-KINASE; OXIDATIVE DNA-DAMAGE;
   MACULAR DEGENERATION; TRANS-RESVERATROL; ANTIOXIDANT ACTIVITY;
   DOWN-REGULATION; MITOCHONDRIAL BIOGENESIS
AB Eye diseases are currently a major public health concern due to the growing number of cases resulting from both an aging of populations and exogenous factors linked to our lifestyles. Thus, many treatments including surgical pharmacological approaches have emerged, and special attention has been paid to prevention, where diet plays a preponderant role. Recently, potential antioxidants such as resveratrol have received much attention as potential tools against various ocular diseases. In this review, we focus on the mechanisms of resveratrol against ocular diseases, in particular age-related macular degeneration, glaucoma, cataract, diabetic retinopathy, and vitreoretinopathy. We analyze, in relation to the different steps of each disease, the resveratrol properties at multiple levels, such as cellular and molecular signaling as well as physiological effects. We show and discuss the relationship to reactive oxygen species, the regulation of inflammatory process, and how resveratrol can prevent ocular diseases through a potential epigenetic action by the activation of sirtuin-1. Lastly, various new forms of resveratrol delivery are emerging at the same time as some clinical trials are raising more questions about the future of resveratrol as a potential tool for prevention or in therapeutic strategies against ocular diseases. More preclinical studies are required to provide further insights into RSV's potential adjuvant activity.
C1 [Delmas, Dominique; Cornebise, Clarisse; Courtaut, Flavie; Aires, Virginie] Univ Bourgogne Franche Comte, F-21000 Dijon, France.
   [Delmas, Dominique; Cornebise, Clarisse; Courtaut, Flavie; Aires, Virginie] INSERM, Res Ctr U1231, Canc & Adapt Immune Response Team, Bioact Mol & Hlth Res Grp, F-21000 Dijon, France.
   [Delmas, Dominique] Ctr Anticancereux Georges Francois Leclerc, F-21000 Dijon, France.
   [Xiao, Jianbo] Univ Vigo, Fac Food Sci & Technol, Dept Analyt Chem & Food Sci, Nutr & Bromatol Grp, Ourense Campus, E-32004 Orense, Spain.
   [Xiao, Jianbo] Guangdong Ocean Univ, Coll Food Sci & Technol, Zhanjiang 524088, Peoples R China.
   [Xiao, Jianbo] Jiangsu Univ, Int Res Ctr Food Nutr & Safety, Zhenjiang 212013, Jiangsu, Peoples R China.
C3 Institut Agro; AgroSup Dijon; Institut National de la Sante et de la
   Recherche Medicale (Inserm); Universite de Bourgogne; UNICANCER; Centre
   Georges-Francois Leclerc; Universidade de Vigo; Guangdong Ocean
   University; Jiangsu University
RP Delmas, D (通讯作者)，Univ Bourgogne Franche Comte, F-21000 Dijon, France.; Delmas, D (通讯作者)，INSERM, Res Ctr U1231, Canc & Adapt Immune Response Team, Bioact Mol & Hlth Res Grp, F-21000 Dijon, France.; Delmas, D (通讯作者)，Ctr Anticancereux Georges Francois Leclerc, F-21000 Dijon, France.
EM dominique.delmas@u-bourgogne.fr; clarisse.cornebise@gmail.com;
   flavie.courtaut@gmail.com; jianboxiao@yahoo.com;
   virginie.aires02@u-bourgogne.fr
RI Xiao, Jianbo/C-7323-2012; Xiao, Jian/GYU-4351-2022
OI Xiao, Jianbo/0000-0003-3311-770X; Delmas, Dominique/0000-0002-8911-8499
FU ANRT [2016/0003]; French Government [ANR-11-LABX-0021]; Conseil Regional
   Bourgogne, Franche-Comte; FEDER (European Funding for Regional Economic
   Development); "Bureau Interprofessionnel des Vins de Bourgogne" (BIVB)
FX This work was supported by grants from the ANRT No 2016/0003, 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, Franche-Comte, the
   FEDER (European Funding for Regional Economic Development), and the
   "Bureau Interprofessionnel des Vins de Bourgogne" (BIVB). The authors
   thank Miss Isabella Athanassiou for valuable English corrections.
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NR 194
TC 22
Z9 23
U1 0
U2 10
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD FEB
PY 2021
VL 22
IS 3
AR 1295
DI 10.3390/ijms22031295
PG 29
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA QD3GE
UT WOS:000615410400001
PM 33525499
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Wolk, A
   Hatipoglu, D
   Cutler, A
   Ali, M
   Bell, L
   Qi, JH
   Singh, R
   Batoki, J
   Karle, L
   Bonilha, VL
   Wessely, O
   Stoehr, H
   Hascall, V
   Anand-Apte, B
AF Wolk, Alyson
   Hatipoglu, Dilara
   Cutler, Alecia
   Ali, Mariya
   Bell, Lestella
   Qi, Jian Hua
   Singh, Rupesh
   Batoki, Julia
   Karle, Laura
   Bonilha, Vera L.
   Wessely, Oliver
   Stoehr, Heidi
   Hascall, Vincent
   Anand-Apte, Bela
TI Role of FGF and Hyaluronan in Choroidal Neovascularization in Sorsby
   Fundus Dystrophy
SO CELLS
LA English
DT Article
DE sorsby's fundus dystrophy; hyaluronan; neovascularization; retina
ID LACKING TISSUE INHIBITOR; METALLOPROTEINASES-3 TIMP3; SULFATED
   GLYCOSAMINOGLYCANS; BRUCHS MEMBRANE; MUTATION; LOCALIZATION; EXPRESSION;
   SYNTHASES; ANGIOGENESIS; ACCUMULATION
AB Sorsby's fundus dystrophy (SFD) is an inherited blinding disorder caused by mutations in the tissue inhibitor of metalloproteinase-3 (TIMP3) gene. The SFD pathology of macular degeneration with subretinal deposits and choroidal neovascularization (CNV) closely resembles that of the more common age-related macular degeneration (AMD). The objective of this study was to gain further insight into the molecular mechanism(s) by which mutant TIMP3 induces CNV. In this study we demonstrate that hyaluronan (HA), a large glycosaminoglycan, is elevated in the plasma and retinal pigment epithelium (RPE)/choroid of patients with AMD. Mice carrying the S179C-TIMP3 mutation also showed increased plasma levels of HA as well as accumulation of HA around the RPE in the retina. Human RPE cells expressing the S179C-TIMP3 mutation accumulated HA apically, intracellularly and basally when cultured long-term compared with cells expressing wildtype TIMP3. We recently reported that RPE cells carrying the S179C-TIMP3 mutation have the propensity to induce angiogenesis via basic fibroblast growth factor (FGF-2). We now demonstrate that FGF-2 induces accumulation of HA in RPE cells. These results suggest that the TIMP3-MMP-FGF-2-HA axis may have an important role in the pathogenesis of CNV in SFD and possibly AMD.
C1 [Wolk, Alyson; Hatipoglu, Dilara; Cutler, Alecia; Ali, Mariya; Bell, Lestella; Qi, Jian Hua; Singh, Rupesh; Batoki, Julia; Karle, Laura; Bonilha, Vera L.; Anand-Apte, Bela] Cleveland Clin Fdn, Cole Eye Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA.
   [Wolk, Alyson; Hatipoglu, Dilara; Cutler, Alecia; Ali, Mariya; Bell, Lestella; Qi, Jian Hua; Singh, Rupesh; Batoki, Julia; Karle, Laura; Bonilha, Vera L.; Anand-Apte, Bela] Cleveland Clin Fdn, Lerner Res Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA.
   [Wolk, Alyson; Bonilha, Vera L.; Wessely, Oliver; Anand-Apte, Bela] Case Western Reserve Univ, Cleveland Clin Lerner Coll Med, Dept Mol Med, Cleveland, OH 44195 USA.
   [Bell, Lestella; Bonilha, Vera L.; Anand-Apte, Bela] Case Western Reserve Univ, Lerner Coll Med, Cleveland Clin, Dept Ophthalmol, Cleveland, OH 44195 USA.
   [Wessely, Oliver] Cleveland Clin Fdn, Lerner Res Inst, Dept Cardiovasc & Metab Sci, 9500 Euclid Ave, Cleveland, OH 44195 USA.
   [Stoehr, Heidi] Univ Regensburg, Inst Human Genet, D-93053 Regensburg, Germany.
   [Hascall, Vincent] Cleveland Clin Fdn, Lerner Res Inst, Dept Biomed Engn, 9500 Euclid Ave, Cleveland, OH 44195 USA.
C3 Cleveland Clinic Foundation; Cleveland Clinic Foundation; Case Western
   Reserve University; Cleveland Clinic Foundation; Case Western Reserve
   University; Cleveland Clinic Foundation; Cleveland Clinic Foundation;
   University of Regensburg; Cleveland Clinic Foundation
RP Anand-Apte, B (通讯作者)，Cleveland Clin Fdn, Cole Eye Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA.; Anand-Apte, B (通讯作者)，Cleveland Clin Fdn, Lerner Res Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA.; Anand-Apte, B (通讯作者)，Case Western Reserve Univ, Cleveland Clin Lerner Coll Med, Dept Mol Med, Cleveland, OH 44195 USA.; Anand-Apte, B (通讯作者)，Case Western Reserve Univ, Lerner Coll Med, Cleveland Clin, Dept Ophthalmol, Cleveland, OH 44195 USA.
EM wolka@ccf.org; Hatipod@ccf.org; cutlera@ccf.org; alim2@ccf.org;
   belll3@ccf.org; qij@ccf.org; Singhr4@ccf.org; Batokij@ccf.org;
   lauraikarle@gmail.com; bonilhav@ccf.org; Wesselo@ccf.org;
   Heidi.Stoehr@klinik.uni-regensburg.de; Hascalv@ccf.org; anandab@ccf.org
RI Bonilha, Vera/AAS-8566-2020
OI Bonilha, Vera/0000-0002-6166-5124; Anand-Apte, Bela/0000-0002-4845-9094;
   Singh, Rupesh/0000-0002-0938-9388; Hatipoglu,
   Dilara/0000-0003-2083-1293; Wolk, Alyson/0000-0002-1613-0251
FU US National Institute of Health [EY027083, EY026181, P30EY025585,
   T32EY024236, EY022768, EY027750]; Research to Prevent Blindness (RPB)
   Challenge Grant; RPB Lew Wasserman award; Cleveland Eye Bank Foundation;
   Cleveland Clinic Foundation
FX This work was supported in part by US National Institute of Health
   EY027083 (BA-A), EY026181 (BA-A), P30EY025585(BA-A), T32EY024236 (AW),
   EY022768 (JHQ), EY027750 (VLB), Research to Prevent Blindness (RPB)
   Challenge Grant and RPB Lew Wasserman award to BA-A, Cleveland Eye Bank
   Foundation Grant and funds from Cleveland Clinic Foundation.
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NR 61
TC 3
Z9 3
U1 0
U2 4
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2073-4409
J9 CELLS-BASEL
JI Cells
PD MAR
PY 2020
VL 9
IS 3
AR 608
DI 10.3390/cells9030608
PG 15
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA LI2TV
UT WOS:000529337400085
PM 32143276
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Garranzo-Asensio, M
   Montero-Calle, A
   Solis-Fernandez, G
   Barderas, R
   Guzman-Aranguez, A
AF Garranzo-Asensio, Maria
   Montero-Calle, Ana
   Solis-Fernandez, Guillermo
   Barderas, Rodrigo
   Guzman-Aranguez, Ana
TI Protein Microarrays: Valuable Tools for Ocular Diseases Research
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Review
DE Protein microarrays; ocular pathology; dry eye; glaucoma; age-related
   macular degeneration; diabetic retinopathy
ID DRY EYE PATIENTS; ANGLE-CLOSURE GLAUCOMA; HUMOR CYTOKINE LEVELS;
   AQUEOUS-HUMOR; INFLAMMATORY CYTOKINES; MACULAR DEGENERATION; MOUSE
   MODEL; INTRAVITREAL TRIAMCINOLONE; SERUM AUTOANTIBODIES;
   COLORECTAL-CANCER
AB The eye is a complex organ comprised of several compartments with exclusive and specialized properties that reflect their diverse functions. Although the prevalence of eye pathologies is increasing, mainly because of its correlation with aging and of generalized lifestyle changes, the pathogenic molecular mechanisms of many common ocular diseases remain poorly understood. Therefore, there is an unmet need to delve into the pathogenesis, diagnosis, and treatment of eye diseases to preserve ocular health and reduce the incidence of visual impairment or blindness. Proteomics analysis stands as a valuable tool for deciphering protein profiles related to specific ocular conditions. In turn, such profiles can lead to real breakthroughs in the fields of ocular science and ophthalmology. Among proteomics techniques, protein microarray technology stands out by providing expanded information using very small volumes of samples.
   In this review, we present a brief summary of the main types of protein microarrays and their application for the identification of protein changes in chronic ocular diseases such as thy eye, glaucoma, age-related macular degeneration, or diabetic retinopathy. The validation of these specific protein alterations could provide new biomarkers, disclose eye diseases pathways, and help in the diagnosis and development of novel therapies for eye pathologies.
C1 [Garranzo-Asensio, Maria; Guzman-Aranguez, Ana] Univ Complutense Madrid, Fac Opt & Optometry, Dept Biochem & Mol Biol, C Arcos de Jalon 118, Madrid 28037, Spain.
   [Garranzo-Asensio, Maria; Montero-Calle, Ana; Solis-Fernandez, Guillermo; Barderas, Rodrigo] Inst Salud Carlos III, Funct Prote Unit, Chron Dis Programme UFIEC, Madrid, Spain.
C3 Complutense University of Madrid; Instituto de Salud Carlos III; Unidad
   Funcional de Investigacion de Enfermedades Cronicas (UFIEC)
RP Guzman-Aranguez, A (通讯作者)，Univ Complutense Madrid, Fac Opt & Optometry, Dept Biochem & Mol Biol, C Arcos de Jalon 118, Madrid 28037, Spain.
EM aguzman@opt.ucm.es
RI Barderas, Rodrigo/K-3560-2014
OI Barderas, Rodrigo/0000-0003-3539-7469; Montero Calle,
   Ana/0000-0001-5141-0454; Solis Fernandez, Guillermo/0000-0002-4785-0040;
   Guzman-Aranguez, Ana/0000-0001-6722-2044
FU Fondo Europeo de Desarrollo Regional-FEDER from the Spanish Ministry of
   Economy and Competitivity [SAF2014-53209-R, SAF2016-77084-R]; Instituto
   de Salud Carlos III [RETICS RD16/0008/0001, FIS-PI13/02177,
   PI17CIII/00045-UFIEC PY 124/18]; Spanish Ministerio de Educacion,
   Cultura y Deporte, Madrid, Spain
FX This work has been supported by grants co-founded by Fondo Europeo de
   Desarrollo Regional-FEDER, SAF2014-53209-R and SAF2016-77084-R from the
   Spanish Ministry of Economy and Competitivity; RETICS RD16/0008/0001,
   FIS-PI13/02177 and PI17CIII/00045-UFIEC PY 124/18 from Instituto de
   Salud Carlos III; A.M.C. FPU predoctoral contract is supported by the
   Spanish Ministerio de Educacion, Cultura y Deporte, Madrid, Spain.
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NR 125
TC 0
Z9 0
U1 2
U2 14
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 2020
VL 27
IS 27
BP 4549
EP 4566
DI 10.2174/0929867326666190627131300
PG 18
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
   Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA MX7HN
UT WOS:000557891800009
PM 31244416
DA 2022-11-30
ER

PT J
AU Brinks, MV
   Redd, T
   Lambert, WE
   Zaback, T
   Randall, J
   Field, T
   Wilson, D
AF Brinks, Mitchell V.
   Redd, Travis
   Lambert, William E.
   Zaback, Tosha
   Randall, Joan
   Field, Teresa
   Wilson, David
TI Using registry data to characterize the incidence and causes of
   blindness in Oregon
SO PLOS ONE
LA English
DT Article
ID VISUAL IMPAIRMENT; TIME TRENDS
AB In the United States, there is no reliable data to describe the prevalence of eye diseases leading to visual impairment and little active surveillance to address this knowledge gap. Data that is readily available from many state blind registries may provide helpful information on trends and causes of blindness. We analyzed new registrations with the Oregon Commission for the Blind (OCB) and Oregon State Department of Administrative Services (DAS) from 1961 to 2016 for causes of and trends in blindness. Persons with blindness self-refer into the OCB registry and the Oregon State Department of Administrative Services (DAS) includes those receiving social security disability financial support and other state services. Data for 9,273 blind persons registered were analyzed. The most frequent causes of blindness were age related macular degeneration (AMD) 3,308 (38%), followed by diabetic retinopathy (DR) 729 (8%), congenital conditions 697 (8%), optic nerve atrophy 611 (7%), glaucoma 549 (6%), retinitis pigmentosa 546 (6%), retinopathy of prematurity192 (2%), cataract 180 (2%), and trauma 174 (2%). The mean age of onset of blindness was younger for Blacks (31 years) and Hispanics (33 years) than for Whites (44 years). Analysis of state-based registries can provide useful and locally relevant vision and eye health data where little information is otherwise available.
C1 [Brinks, Mitchell V.; Redd, Travis; Zaback, Tosha; Randall, Joan; Wilson, David] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA.
   [Lambert, William E.] Oregon Hlth & Sci Univ, Sch Publ Hlth, Portland, OR 97201 USA.
   [Field, Teresa] Oregon Commiss Blind, Portland, OR USA.
C3 Oregon Health & Science University; Oregon Health & Science University
RP Brinks, MV (通讯作者)，Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA.
EM brinks@ohsu.edu
OI Zaback, Tosha/0000-0003-2028-9684
FU Research to Prevent Blindness (New York, NY)
FX This study was supported by unrestricted departmental funding from
   Research to Prevent Blindness (New York, NY). The funder had no role in
   study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
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NR 20
TC 2
Z9 2
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 8
PY 2019
VL 14
IS 8
AR e0220983
DI 10.1371/journal.pone.0220983
PG 9
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA IW5EW
UT WOS:000485002500090
PM 31393957
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Zhu, X
   Wang, K
   Zhou, FF
   Zhu, L
AF Zhu, Xue
   Wang, Ke
   Zhou, Fanfan
   Zhu, Ling
TI Paeoniflorin attenuates atRAL-induced oxidative stress, mitochondrial
   dysfunction and endoplasmic reticulum stress in retinal pigment
   epithelial cells via triggering Ca2+/CaMKII-dependent activation of AMPK
SO ARCHIVES OF PHARMACAL RESEARCH
LA English
DT Article
DE Paeoniflorin; All-trans-retinal; RPE; AMPK
ID PROTEIN-KINASE; ER STRESS; MACULAR DEGENERATION; CANCER CELLS;
   APOPTOSIS; DISEASES; PATHWAY; SURVIVAL; DAMAGE
AB Abnormal accumulation of the free-form all-trans-retinal (atRAL), a major intermediate of human visual cycle, is considered to be a key cause of retinal pigment epithelial (RPE) dysfunction in the pathogenesis of retinal degenerative diseases such as age-related macular degeneration (AMD). Paeoniflorin (PF), a monoterpene glucoside isolated from Paeonia lactiflora Pall., has been used in clinical treatment of retinal degenerative diseases in China for several years; however, the underlying mechanism remains unclear. The aim of this study is to investigate the protective effect of PF against atRAL toxicity in human ARPE-19 cells and its molecular mechanism. The results of our study showed that the pre-treatment of PF dose-dependently attenuated atRAL-induced cell injury by the reduction of Nox1/ROS-associated oxidative stress, mitochondrial dysfunction and GRP78-PERK-eIF2-ATF4-CHOP-regulated endoplasmic reticulum (ER) stress in ARPE-19 cells. Additionally, our data showed that PF mainly exerted its activity via triggering calcium-calmodulin dependent protein kinase II (CaMKII)-mediated activation of AMP-activated protein kinase (AMPK). AMPK inhibition significantly reversed the protective effect of PF against atRAL toxicity in ARPE-19 cells. Overall, our findings provided the novel mechanism of PF protecting human RPE cells, which may prevent the progression of retinal degenerative diseases.
C1 [Zhu, Xue; Wang, Ke] Jiangsu Inst Nucl Med, Key Lab Nucl Med, Jiangsu Key Lab Mol Nucl Med, Minist Hlth, Wuxi 214063, Jiangsu, Peoples R China.
   [Zhou, Fanfan] Univ Sydney, Fac Med & Hlth, Sch Pharm, Sydney, NSW 2006, Australia.
   [Zhu, Ling] Univ Sydney, Fac Med & Hlth, Save Sight Inst, Sydney, NSW 2000, Australia.
C3 University of Sydney; University of Sydney
RP Wang, K (通讯作者)，Jiangsu Inst Nucl Med, Key Lab Nucl Med, Jiangsu Key Lab Mol Nucl Med, Minist Hlth, Wuxi 214063, Jiangsu, Peoples R China.
EM wangke@jsinm.org
RI Zhou, Fanfan/J-2327-2019; Zhu, Xue/AAR-9416-2020; Zhu, Ling/M-3887-2013
OI Zhou, Fanfan/0000-0002-1982-1541; Zhu, Ling/0000-0003-0776-1630; Wang,
   Ke/0000-0003-3812-7018
FU Major Project of Wuxi Municipal Health Bureau [Z201508]; Project of Wuxi
   Municipal Science and Technology Bureau [CSE31N1520, CSE31N1621];
   National Natural Science Foundation of China [81770941]
FX This work was supported by the Major Project of Wuxi Municipal Health
   Bureau (Z201508), the Project of Wuxi Municipal Science and Technology
   Bureau (CSE31N1520 and CSE31N1621), and the National Natural Science
   Foundation of China (81770941).
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NR 32
TC 24
Z9 27
U1 1
U2 24
PU PHARMACEUTICAL SOC KOREA
PI SEOUL
PA 1489-3 SUHCHO-DONG, SUHCHO-KU, SEOUL 137-071, SOUTH KOREA
SN 0253-6269
EI 1976-3786
J9 ARCH PHARM RES
JI Arch. Pharm. Res.
PD OCT
PY 2018
VL 41
IS 10
BP 1009
EP 1018
DI 10.1007/s12272-018-1059-6
PG 10
WC Chemistry, Medicinal; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA GU3NF
UT WOS:000445185100007
PM 30117083
DA 2022-11-30
ER

PT J
AU Providencia, J
   Rodrigues, TM
   Oliveira, M
   Bernardes, J
   Marques, JP
   Murta, J
   Silva, R
AF Providencia, Joana
   Rodrigues, Tiago M.
   Oliveira, Mariana
   Bernardes, Joao
   Marques, Joao Pedro
   Murta, Joaquim
   Silva, Rufino
TI Real-World Results of Aflibercept versus Ranibizumab for the Treatment
   of Exudative AMD Using a Fixed Regimen
SO BIOMED RESEARCH INTERNATIONAL
LA English
DT Article
ID MACULAR DEGENERATION; METAANALYSIS; PREVALENCE; BURDEN; EYE
AB Intravitreal injections of antivascular endothelial growth factors have been considered a milestone in the treatment of neovascular age-related macular degeneration (nAMD). However, the increasing incidence of AMD and the burden of visits and injections overcharge both the patient and the healthcare systems. Real-world solutions depend on treatment protocols aimed at optimizing the number of clinical visits while guaranteeing good functional outcomes. We performed a retrospective analysis of 72 eyes from 63 naive patients diagnosed with nAMD that underwent a fixed intravitreal protocol consisting of bimonthly injections after a three-month loading dose, with either Aflibercept or Ranibizumab (no predefined criteria for treatment selection). Best corrected visual acuity (BCVA) and optical coherence tomography were analyzed at baseline and during follow-up clinical visits (months 3, 6, 12, and 18). From the included participants, 42 followed a fixed regimen with Aflibercept and 30 with Ranibizumab. At the 12-month visit, there was not a statistically significant difference in the mean change of BCVA between the two groups (p=0.121); however, the mean difference in the central retinal thickness was significantly superior in the Aflibercept group (-142.2 versus -51.5, p=0.011). The described fixed regimen seems to be efficient in the treatment of nAMD in a clinical practice setting.
C1 [Providencia, Joana; Rodrigues, Tiago M.; Oliveira, Mariana; Bernardes, Joao; Marques, Joao Pedro; Murta, Joaquim; Silva, Rufino] Ctr Hosp & Univ Coimbra, Dept Ophthalmol, Coimbra, Portugal.
   [Rodrigues, Tiago M.] Univ Lisbon, Fac Med, Inst Med Mol, Lisbon, Portugal.
   [Marques, Joao Pedro; Murta, Joaquim; Silva, Rufino] Univ Coimbra, Fac Med, Coimbra, Portugal.
   [Marques, Joao Pedro; Murta, Joaquim; Silva, Rufino] Assoc Innovat & Biomed Res Light AIBILI, Coimbra, Portugal.
C3 Universidade de Coimbra; Centro Hospitalar e Universitario de Coimbra
   (CHUC); Universidade de Lisboa; Universidade de Coimbra; Universidade de
   Coimbra
RP Providencia, J (通讯作者)，Ctr Hosp & Univ Coimbra, Dept Ophthalmol, Coimbra, Portugal.
EM joanaprovidenciacosta@gmail.com
RI Marques, João Pedro/J-3584-2012; Silva, Rufino M/J-2817-2012; Murta,
   Joaquim/V-5494-2017
OI Marques, João Pedro/0000-0002-1014-0483; Silva, Rufino
   M/0000-0001-8676-0833; Murta, Joaquim/0000-0001-8926-5176; Rodrigues,
   Tiago M./0000-0002-0973-9763; Providencia, Joana/0000-0003-1312-7978
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NR 18
TC 9
Z9 9
U1 0
U2 1
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 2314-6133
EI 2314-6141
J9 BIOMED RES INT
JI Biomed Res. Int.
PY 2018
VL 2018
AR 9276580
DI 10.1155/2018/9276580
PG 7
WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Research & Experimental Medicine
GA GI5IS
UT WOS:000434404800001
PM 29984251
OA gold, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Liberatore, F
   Bucci, D
   Mascio, G
   Madonna, M
   Di Pietro, P
   Beneventano, M
   Puliti, AM
   Battaglia, G
   Bruno, V
   Nicoletti, F
   Romano, MR
AF Liberatore, Francesca
   Bucci, Domenico
   Mascio, Giada
   Madonna, Michele
   Di Pietro, Paola
   Beneventano, Martina
   Puliti, Alda Maria
   Battaglia, Giuseppe
   Bruno, Valeria
   Nicoletti, Ferdinando
   Romano, Maria Rosaria
TI PERMISSIVE ROLE FOR MGLU1 METABOTROPIC GLUTAMATE RECEPTORS IN
   EXCITOTOXIC RETINAL DEGENERATION
SO NEUROSCIENCE
LA English
DT Article
DE retinal ganglion cells; mGlu1 receptors; monosodium glutamate;
   JNJ16258695; crv4 mice
ID CYCLASE ACTIVATING POLYPEPTIDE; FOCAL CEREBRAL-ISCHEMIA; LONG-TERM
   DEPRESSION; MONOSODIUM-GLUTAMATE; NMDA RECEPTOR; ANTAGONIST;
   NEUROPROTECTION; GLAUCOMA; LESION; INJURY
AB Neuroprotection is an unmet need in eye disorders characterized by retinal ganglion cell (RGC) death, such as prematurity-induced retinal degeneration, glaucoma, and age-related macular degeneration. In all these disorders excitotoxicity is a prominent component of neuronal damage, but clinical data discourage the development of NMDA receptor antagonists as neuroprotectants. Here, we show that activation of mGlu1 metabotropic glutamate receptors largely contributes to excitotoxic degeneration of RGCs. Mice at postnatal day 9 were challenged with a toxic dose of monosodium glutamate (MSG, 3 g/kg), which caused the death of >70% of Brn-3a(+) RGCs. Systemic administration of the mGlu1 receptor negative allosteric modulator (NAM), JNJ16259685 (2.5 mg/kg, s.c.), was largely protective against MSG-induced RGC death. This treatment did not cause changes in motor behavior in the pups. We also injected MSG to crv4 mice, which lack mGlu1 receptors because of a recessive mutation of the gene encoding the mGlu1 receptor. MSG did not cause retinal degeneration in crv4 mice, whereas it retained its toxic activity in their wild-type littermates. These findings demonstrate that mGlu1 receptors play a key role in excitotoxic degeneration of RGCs, and encourage the study of mGlu1 receptor NAMs in models of retinal neurodegeneration. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
C1 [Liberatore, Francesca; Bruno, Valeria; Nicoletti, Ferdinando] Sapienza Univ Rome, Dept Physiol & Pharmacol, Rome, Italy.
   [Bucci, Domenico; Mascio, Giada; Madonna, Michele; Di Pietro, Paola; Battaglia, Giuseppe; Bruno, Valeria; Nicoletti, Ferdinando; Romano, Maria Rosaria] IRCCS Neuromed, Pozzilli, IS, Italy.
   [Beneventano, Martina] Univ Catania, Dept Biomed & Biotechnol Sci, Sect Pharmacol, Catania, Italy.
   [Puliti, Alda Maria] Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, Genoa, Italy.
   [Puliti, Alda Maria] Ist Giannina Gaslini, UOC Genet Med, Genoa, Italy.
C3 Sapienza University Rome; IRCCS Neuromed; University of Catania;
   University of Genoa; University of Genoa; IRCCS Istituto Giannina
   Gaslini
RP Nicoletti, F (通讯作者)，Univ Sapienza Rome, Dept Physiol & Pharmacol, Piazzale Aldo Moro, I-00185 Rome, Italy.
EM ferdinandonicoletti@hotmail.com
RI bruno, Valeria/F-3146-2012; Bucci, Domenico/G-6747-2011; Di Pietro,
   Paola/K-5137-2016; Puliti, Aldamaria/K-7866-2016; Bucci,
   Domenico/AAA-5475-2019; Di Pietro, Paola/ACH-4882-2022; Mascio,
   Giada/Z-2211-2019; Liberatore, Francesca/AAB-5645-2019; Puliti,
   Aldamaria/AAF-5400-2021; Mascio, Giada/J-2294-2018; Nicoletti,
   Ferdinando/T-4898-2019; Battaglia, Giuseppe/A-7709-2010
OI bruno, Valeria/0000-0003-4231-0739; Di Pietro,
   Paola/0000-0003-1327-1961; Puliti, Aldamaria/0000-0001-9310-6514; Bucci,
   Domenico/0000-0003-3239-2435; Di Pietro, Paola/0000-0003-1327-1961;
   Mascio, Giada/0000-0001-7556-436X; Mascio, Giada/0000-0001-7556-436X;
   Battaglia, Giuseppe/0000-0001-7571-3417; Madonna,
   Michele/0000-0003-1319-3932; Liberatore, Francesca/0000-0001-8941-0740
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NR 56
TC 10
Z9 10
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
EI 1873-7544
J9 NEUROSCIENCE
JI Neuroscience
PD NOV 5
PY 2017
VL 363
BP 142
EP 149
DI 10.1016/j.neuroscience.2017.09.005
PG 8
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA FK9IN
UT WOS:000413824900015
PM 28918254
OA Green Published
DA 2022-11-30
ER

PT J
AU Corso, L
   Cavallero, A
   Baroni, D
   Garbati, P
   Prestipino, G
   Bisti, S
   Nobile, M
   Picco, C
AF Corso, Lucia
   Cavallero, Anna
   Baroni, Debora
   Garbati, Patrizia
   Prestipino, Gianfranco
   Bisti, Silvia
   Nobile, Mario
   Picco, Cristiana
TI Saffron reduces ATP-induced retinal cytotoxicity by targeting P2X7
   receptors
SO PURINERGIC SIGNALLING
LA English
DT Article
DE P2X7 receptor; Retinal cells; Saffron; Neurodegenerative disease
ID CROCUS-SATIVUS L.; P2X(7) RECEPTOR; PURINERGIC RECEPTORS; MACULAR
   DEGENERATION; OXIDATIVE DAMAGE; GANGLION-CELLS; RAT RETINA; CALCIUM;
   DEATH; SUPPLEMENTATION
AB P2X7-type purinergic receptors are distributed throughout the nervous system where they contribute to physiological and pathological functions. In the retina, this receptor is found in both inner and outer cells including microglia modulating signaling and health of retinal cells. It is involved in retinal neurodegenerative disorders such as retinitis pigmentosa and age-related macular degeneration (AMD). Experimental studies demonstrated that saffron protects photoreceptors from light-induced damage preserving both retinal morphology and visual function and improves retinal flicker sensitivity in AMD patients. To evaluate a possible interaction between saffron and P2X7 receptors (P2X7Rs), different cellular models and experimental approaches were used. We found that saffron positively influences the viability of mouse primary retinal cells and photoreceptor-derived 661W cells exposed to ATP, and reduced the ATP-induced intracellular calcium increase in 661W cells. Similar results were obtained on HEK cells transfected with recombinant rat P2X7R but not on cells transfected with rat P2X2R. Finally, patch-clamp experiments showed that saffron inhibited cationic currents in HEK-P2X7R cells. These results point out a novel mechanism through which saffron may exert its protective role in neurodegeneration and support the idea that P2X7-mediated calcium signaling may be a crucial therapeutic target in the treatment of neurodegenerative diseases.
C1 [Corso, Lucia; Cavallero, Anna; Baroni, Debora; Garbati, Patrizia; Prestipino, Gianfranco; Nobile, Mario; Picco, Cristiana] CNR, Inst Biophys, Via De Marini 6, I-16149 Genoa, Italy.
   [Corso, Lucia; Bisti, Silvia] Univ Aquila, DISCAB, Dept Biotechnol & Appl Clin Sci, I-67100 Laquila, Italy.
C3 Consiglio Nazionale delle Ricerche (CNR); Istituto di Biofisica
   (IBF-CNR); University of L'Aquila
RP Picco, C (通讯作者)，CNR, Inst Biophys, Via De Marini 6, I-16149 Genoa, Italy.
EM picco@ge.ibf.cnr.it
RI baroni, debora/ABA-7170-2020; baroni, debora/AEU-4703-2022
OI baroni, debora/0000-0001-8764-2468; Corso, Lucia/0000-0003-4368-0723;
   Garbati, Patrizia/0000-0002-6175-6915
FU MIUR-PRIN
FX We wish to thank Dr. Maria Maggi (HN s.r.L.) and Lab of Analytical
   Chemistry, University of L'Aquila, for performing the chemical analysis.
   We thank Dr. Joachim Scholz-Starke (IBF-CNR, Italy) for critical
   comments on the manuscript. The technical assistance of Francesca
   Quartino and Alessandro Barbin (IBF-CNR, Italy) was highly appreciated.
   This study was supported by MIUR-PRIN (2010-2011) research grant to SB.
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NR 46
TC 29
Z9 29
U1 2
U2 17
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1573-9538
EI 1573-9546
J9 PURINERG SIGNAL
JI Purinergic Signal.
PD MAR
PY 2016
VL 12
IS 1
BP 161
EP 174
DI 10.1007/s11302-015-9490-3
PG 14
WC Biochemistry & Molecular Biology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DD6ZW
UT WOS:000370074400012
PM 26739703
OA Green Published
DA 2022-11-30
ER

PT J
AU Tsilimbaris, MK
   Lopez-Galvez, MI
   Gallego-Pinazo, R
   Margaron, P
   Lambrou, GN
AF Tsilimbaris, Miltiadis K.
   Lopez-Galvez, Maria I.
   Gallego-Pinazo, Roberto
   Margaron, Philippe
   Lambrou, George N.
TI Epidemiological and Clinical Baseline Characteristics as Predictive
   Biomarkers of Response to Anti-VEGF Treatment in Patients with
   Neovascular AMD
SO JOURNAL OF OPHTHALMOLOGY
LA English
DT Review
ID ENDOTHELIAL GROWTH-FACTOR; INTRAVITREAL BEVACIZUMAB AVASTIN; PIGMENT
   EPITHELIAL DETACHMENT; OPTICAL COHERENCE TOMOGRAPHY; 2.0 MG RANIBIZUMAB;
   MACULAR DEGENERATION; VISUAL IMPAIRMENT; SUBGROUP ANALYSIS; EXUDATIVE
   AMD; THERAPY
AB Purpose. To review the current literature investigating patient response to antivascular endothelial growth factor-A (VEGF) therapy in the treatment of neovascular age-related macular degeneration (nAMD) and to identify baseline characteristics that might predict response. Method. A literature search of the PubMed database was performed, using the keywords: AMD, anti-VEGF, biomarker, optical coherence tomography, treatment outcome, and predictor. The search was limited to articles published from 2006 to date. Exclusion criteria included phase 1 trials, case reports, studies focusing on indications other than nAMD, and oncology. Results. A total of 1467 articles were identified, of which 845 were excluded. Of the 622 remaining references, 47 met all the search criteria and were included in this review. Conclusion. Several baseline characteristics correlated with anti-VEGF treatment response, including best-corrected visual acuity, age, lesion size, and retinal thickness. The majority of factors were associated with disease duration, suggesting that longer disease duration before treatment results in worse treatment outcomes. This highlights the need for early treatment for patients with nAMD to gain optimal treatment outcomes. Many of the identified baseline characteristics are interconnected and cannot be evaluated in isolation; therefore multivariate analyses will be required to determine any specific relationship with treatment response.
C1 [Tsilimbaris, Miltiadis K.] Univ Crete, Sch Med, Dept Ophthalmol, Iraklion 70013, Crete, Greece.
   [Lopez-Galvez, Maria I.] Univ Valladolid, HCU, Dept Ophthalmol, Valladolid, Spain.
   [Lopez-Galvez, Maria I.] Univ Valladolid, IOBA, Valladolid, Spain.
   [Gallego-Pinazo, Roberto] Univ Valencia, Dept Ophthalmol, Unit Macula, Valencia, Spain.
   [Gallego-Pinazo, Roberto] Polytech Hosp La Fe, Valencia, Spain.
   [Margaron, Philippe] Novartis Pharma AG, Basel, Switzerland.
   [Lambrou, George N.] Natl Ctr Ophthalmol, Vis Inst, Paris, France.
C3 University of Crete; Universidad de Valladolid; Universidad de
   Valladolid; University of Valencia; Novartis; UDICE-French Research
   Universities; Sorbonne Universite
RP Tsilimbaris, MK (通讯作者)，Univ Crete, Sch Med, Dept Ophthalmol, Iraklion 70013, Crete, Greece.
EM tsilimb@med.uoc.gr
OI Tsilimbaris, Miltiadis/0000-0002-0130-1150
FU Novartis Pharma AG, Basel, Switzerland
FX Editorial support was provided by Fishawack Communications Ltd., Oxford,
   UK; this service was funded by Novartis Pharma AG, Basel, Switzerland.
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NR 76
TC 24
Z9 24
U1 0
U2 3
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 2016
VL 2016
AR 4367631
DI 10.1155/2016/4367631
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DH7ZR
UT WOS:000373013400001
PM 27073691
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Park, SW
   Kim, JH
   Park, SM
   Moon, M
   Lee, K
   Park, KH
   Park, WJ
   Kim, JH
AF Park, Sung Wook
   Kim, Jin Hyoung
   Park, Sang Min
   Moon, Minho
   Lee, Kihwang
   Park, Kyu Hyung
   Park, Woo Jin
   Kim, Jeong Hun
TI RAGE mediated intracellular A beta uptake contributes to the breakdown
   of tight junction in retinal pigment epithelium
SO ONCOTARGET
LA English
DT Article
DE amyloid beta; age-related macular degeneration; endocytosis; tight
   junction; receptor for advanced glycation end products; Gerotarget
ID BLOOD-BRAIN-BARRIER; AMYLOID-BETA; MACULAR DEGENERATION;
   ALZHEIMERS-DISEASE; CELLS; ACCUMULATION; PEPTIDE; RECEPTOR; BINDING;
   MODEL
AB Intracellular amyloid beta (A beta) has been implicated in neuronal cell death in Alzheimer's disease (AD). Intracellular A beta also contributes to tight junction breakdown of retinal pigment epithelium (RPE) in age-related macular degeneration (AMD). Although A beta is predominantly secreted from neuronal cells, the mechanism of A beta transport into RPE remains to be fully elucidated. In this study, we demonstrated that intracellular A beta was found concomitantly with the breakdown of tight junction in RPE after subretinal injection of A beta into the mouse eye. We also presented evidence that receptor for advanced glycation end products (RAGE) contributed to endocytosis of A beta in RPE. siRNA-mediated knockdown of RAGE prevented intracellular A beta accumulation as well as subsequent tight junction breakdown in RPE. In addition, we found that RAGE-mediated p38 MAPK signaling contributed to endocytosis of A beta. Blockade of RAGE/p38 MAPK signaling inhibited A beta endocytosis, thereby preventing tight junction breakdown in RPE. These results implicate that intracellular A beta contributes to the breakdown of tight junction in RPE via the RAGE/p38 MAPK-mediated endocytosis. Thus, we suggest that RAGE could be a potential therapeutic target for intracellular A beta induced outer BRB breakdown in AMD.
C1 [Park, Sung Wook; Kim, Jin Hyoung; Kim, Jeong Hun] Seoul Natl Univ Hosp, Biomed Res Inst, Fight Angiogenesis Related Blindness Lab, Seoul 110744, South Korea.
   [Park, Sung Wook; Kim, Jeong Hun] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul, South Korea.
   [Park, Sang Min; Park, Woo Jin] Life Sci Concentrat GIST Gwangju Inst Sci & Techn, Dept Life Sci, Gwangju, South Korea.
   [Moon, Minho] Konyang Univ, Coll Med, Dept Biochem, Daejeon, South Korea.
   [Lee, Kihwang] Ajou Univ, Sch Med, Dept Ophthalmol, Suwon, Gyeonggi Do, South Korea.
   [Park, Kyu Hyung; Kim, Jeong Hun] Seoul Natl Univ, Coll Med, Dept Ophthalmol, Seoul, South Korea.
   [Park, Kyu Hyung] Seoul Natl Univ, Bundang Hosp, Dept Ophthalmol, Songnam, Gyeonggi Do, South Korea.
C3 Seoul National University (SNU); Seoul National University Hospital;
   Seoul National University (SNU); Gwangju Institute of Science &
   Technology (GIST); Konyang University; Konyang University Hospital; Ajou
   University; Seoul National University (SNU); Seoul National University
   (SNU)
RP Kim, JH (通讯作者)，Seoul Natl Univ Hosp, Biomed Res Inst, Fight Angiogenesis Related Blindness Lab, Seoul 110744, South Korea.
EM steph25@snu.ac.kr
RI Park, Sung Wook/D-5541-2012; Park, Sang Min/V-9194-2019
OI Park, Sung Wook/0000-0001-8151-6663; Lee, Kihwang/0000-0003-0478-8758;
   Kim, Jeong Hun/0000-0003-2957-1766
FU Seoul National University Research Grant [800-20140542]; MD-PhD program
   of Korea Research Institute of Bioscience and Biotechnology
   [700-2015-2018]; Pioneer Research Program of the National Research
   Foundation of Korea/Ministry of Education, Science and Technology
   [2012-0009544]; Bio & Medical Technology Development Program of the
   National Research Foundation - Korean government, MSIP
   [NRF-2015M3A9E6028949]
FX This study was supported by the Seoul National University Research Grant
   (800-20140542), the MD-PhD program of Korea Research Institute of
   Bioscience and Biotechnology (700-2015-2018), the Pioneer Research
   Program of the National Research Foundation of Korea/Ministry of
   Education, Science and Technology (2012-0009544), the Bio & Medical
   Technology Development Program of the National Research Foundation
   funded by the Korean government, MSIP (NRF-2015M3A9E6028949).
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NR 29
TC 21
Z9 22
U1 0
U2 10
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 NOV 3
PY 2015
VL 6
IS 34
BP 35263
EP 35273
DI 10.18632/oncotarget.5894
PG 11
WC Oncology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Cell Biology
GA CY0QZ
UT WOS:000366111900022
PM 26431165
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Muraleva, NA
   Kozhevnikova, OS
   Zhdankina, AA
   Stefanova, NA
   Karamysheva, TV
   Fursova, AZ
   Kolosova, NG
AF Muraleva, Natalia A.
   Kozhevnikova, Oyuna S.
   Zhdankina, Anna A.
   Stefanova, Natalia A.
   Karamysheva, Tatyana V.
   Fursova, Anzhella Z.
   Kolosova, Nataliya G.
TI The mitochondria-targeted antioxidant SkQ1 restores alpha B-crystallin
   expression and protects against AMD-like retinopathy in OXYS rats
SO CELL CYCLE
LA English
DT Article
DE age-related macular degeneration; alpha-crystallin; alpha B-crystallin;
   SkQ1; OXYS rats
ID RETINAL-PIGMENT EPITHELIUM; OXIDATIVE STRESS; MACULAR DEGENERATION;
   ALZHEIMERS-DISEASE; GENE-EXPRESSION; SENESCENCE; MODEL; DYNAMICS; CELLS;
   VEGF
AB Age-related macular degeneration (AMD), a neurodegenerative and vascular retinal disease, is the leading cause of blindness in the developed world. Accumulating evidence suggests that alterations in the expression of a small heat shock protein (B-crystallin) are involved in the pathogeneses of AMD. Here we demonstrate that senescence-accelerated OXYS ratsan animal model of the dry form of AMDdevelop spontaneous retinopathy against the background of reduced expression of B-crystallin in the retina at the early preclinical stages of retinopathy (age 20days) as well as at 4 and 24 months of age, during the progressive stage of the disease. The level of A-crystallin expression in the retina of OXYS rats at all the ages examined was no different from that in disease-free Wistar rats. Treatment with the mitochondria-targeted antioxidant SkQ1 (plastoquinonyl-decyltriphenylphosphonium) from 1.5 to 4 months of age, 250 nmol/kg, increased the level of B-crystallin expression in the retina of OXYS rats. SkQ1 slowed the development of retinopathy and reduced histological aberrations in retinal pigment epithelium cells. SkQ1 also attenuated neurodegenerative changes in the photoreceptors and facilitated circulation in choroid blood vessels in the retina of OXYS rats; this improvement was probably linked with the restoration of B-crystallin expression.
C1 [Muraleva, Natalia A.; Kozhevnikova, Oyuna S.; Stefanova, Natalia A.; Karamysheva, Tatyana V.; Fursova, Anzhella Z.; Kolosova, Nataliya G.] Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia.
   [Zhdankina, Anna A.] Siberian State Med Univ, Tomsk, Russia.
   [Kolosova, Nataliya G.] Novosibirsk State Univ, Novosibirsk 630090, Russia.
   [Kolosova, Nataliya G.] Inst Mitoengn, Moscow, Russia.
C3 Russian Academy of Sciences; Institute of Cytology & Genetics ICG SB
   RAS; Siberian State Medical University; Novosibirsk State University
RP Kolosova, NG (通讯作者)，Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia.
EM kolosova@bionet.nsc.ru
RI Kolosova, Nataliya G/P-3178-2015; Stefanova, Natalia/V-1530-2018;
   Muraleva, Natalia/S-2392-2018; fursova, anzhella/AAE-1495-2022;
   Kolosova, Nataliya G/AAR-7409-2020; Karamysheva, Tatyana/AAD-4913-2020;
   Kozhevnikova, Oyuna S./H-3588-2016
OI Kolosova, Nataliya G/0000-0003-2398-8544; Muraleva,
   Natalia/0000-0002-0665-1723; fursova, anzhella/0000-0001-6311-5452;
   Kolosova, Nataliya G/0000-0003-2398-8544; Kozhevnikova, Oyuna
   S./0000-0001-6475-4061; Anna, Zhdankina/0000-0002-4954-7416; Stefanova,
   natalia/0000-0001-5127-5993
FU Russian Foundation for Basic Research [14-04-00376A]; Government of the
   Russian Federation [N 2012-220-03-435, N 14.B25.31.0033]
FX This study was supported by the Russian Foundation for Basic Research
   (Grant # 14-04-00376A) and partially by Grants of the Government of the
   Russian Federation N 2012-220-03-435 and N 14.B25.31.0033.
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NR 40
TC 19
Z9 22
U1 0
U2 10
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1538-4101
EI 1551-4005
J9 CELL CYCLE
JI Cell Cycle
PD NOV 15
PY 2014
VL 13
IS 22
BP 3499
EP 3505
DI 10.4161/15384101.2014.958393
PG 7
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA AZ6KM
UT WOS:000348328800009
PM 25483086
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Wert, KJ
   Skeie, JM
   Davis, RJ
   Tsang, SH
   Mahajan, VB
AF Wert, Katherine J.
   Skeie, Jessica M.
   Davis, Richard J.
   Tsang, Stephen H.
   Mahajan, Vinit B.
TI Subretinal Injection of Gene Therapy Vectors and Stem Cells in the
   Perinatal Mouse Eye
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Stem Cell Biology; Issue 69; Medicine; Ophthalmology; Anatomy;
   Physiology; Cellular Biology; Genetics; mouse; subretinal injection; iPS
   cells; stem cells; retina; eye; gene therapy
ID RETINAL DEGENERATION
AB The loss of sight affects approximately 3.4 million people in the United States and is expected to increase in the upcoming years.(1) Recently, gene therapy and stem cell transplantations have become key therapeutic tools for treating blindness resulting from retinal degenerative diseases. Several forms of autologous transplantation for age-related macular degeneration (AMD), such as iris pigment epithelial cell transplantation, have generated encouraging results, and human clinical trials have begun for other forms of gene and stem cell therapies.(2) These include RPE65 gene replacement therapy in patients with Leber's congenital amaurosis and an RPE cell transplantation using human embryonic stem (ES) cells in Stargardt's disease.(3-4) Now that there are gene therapy vectors and stem cells available for treating patients with retinal diseases, it is important to verify these potential therapies in animal models before applying them in human studies. The mouse has become an important scientific model for testing the therapeutic efficacy of gene therapy vectors and stem cell transplantation in the eye.(5-8) In this video article, we present a technique to inject gene therapy vectors or stem cells into the subretinal space of the mouse eye while minimizing damage to the surrounding tissue.
C1 [Wert, Katherine J.; Davis, Richard J.; Tsang, Stephen H.] Columbia Univ, Dept Ophthalmol, Bernard & Shirlee Brown Glaucoma Lab, New York, NY 10027 USA.
   [Wert, Katherine J.] Columbia Univ, Coll Phys & Surg, Inst Human Nutr, New York, NY 10027 USA.
   [Skeie, Jessica M.; Tsang, Stephen H.; Mahajan, Vinit B.] Univ Iowa, Om Lab, Iowa City, IA 52242 USA.
   [Skeie, Jessica M.; Mahajan, Vinit B.] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA 52242 USA.
C3 Columbia University; Columbia University; University of Iowa; University
   of Iowa
RP Mahajan, VB (通讯作者)，Univ Iowa, Om Lab, Iowa City, IA 52242 USA.
EM mahajanlab@gmail.com
OI Wert, Katherine/0000-0002-8430-2916; Mahajan, Vinit/0000-0003-1886-1741
FU Takayuki Nagasaki; NIH [5T32EY013933, 5T32DK007647-20, K08EY020530];
   NATIONAL EYE INSTITUTE [R01EY018213, T32EY013933, K08EY020530,
   F32EY022280] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF
   DIABETES AND DIGESTIVE AND KIDNEY DISEASES [T32DK007647] Funding Source:
   NIH RePORTER
FX Research to Prevent Blindness; Experimental assistance from Takayuki
   Nagasaki; This research complies with the ARVO Statement for the Use of
   Animals in Ophthalmic and Visual Research. KJW is supported by NIH
   grants 5T32EY013933 and 5T32DK007647-20. VBM is supported by NIH grant
   K08EY020530.
CR Abe Toshiaki, 2002, Nippon Ganka Gakkai Zasshi, V106, P778
   [Anonymous], 2011, PREV BLINDN DAT
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NR 12
TC 18
Z9 18
U1 1
U2 8
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 2012
IS 69
AR e4286
DI 10.3791/4286
PG 6
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA V36QM
UT WOS:000209226000027
PM 23207897
OA Green Published
DA 2022-11-30
ER

PT J
AU Kleinman, ME
   Kaneko, H
   Cho, WG
   Dridi, S
   Fowler, BJ
   Blandford, AD
   Albuquerque, RJC
   Hirano, Y
   Terasaki, H
   Kondo, M
   Fujita, T
   Ambati, BK
   Tarallo, V
   Gelfand, BD
   Bogdanovich, S
   Baffi, JZ
   Ambati, J
AF Kleinman, Mark E.
   Kaneko, Hiroki
   Cho, Won Gil
   Dridi, Sami
   Fowler, Benjamin J.
   Blandford, Alexander D.
   Albuquerque, Romulo J. C.
   Hirano, Yoshio
   Terasaki, Hiroko
   Kondo, Mineo
   Fujita, Takashi
   Ambati, Balamurali K.
   Tarallo, Valeria
   Gelfand, Bradley D.
   Bogdanovich, Sasha
   Baffi, Judit Z.
   Ambati, Jayakrishna
TI Short-interfering RNAs Induce Retinal Degeneration via TLR3 and IRF3
SO MOLECULAR THERAPY
LA English
DT Article
ID TOLL-LIKE RECEPTOR-3; DOUBLE-STRANDED-RNA; MACULAR DEGENERATION;
   CHOROIDAL NEOVASCULARIZATION; EPITHELIAL-CELLS; ACTIVATION; SIRNA; GENE;
   RECOGNITION; SUPPRESSION
AB The discovery of sequence-specific gene silencing by endogenous double-stranded RNAs (dsRNA) has propelled synthetic short-interfering RNAs (siRNAs) to the forefront of targeted pharmaceutical engineering. The first clinical trials utilized 21-nucleotide (nt) siRNAs for the treatment of neovascular age-related macular degeneration (AMD). Surprisingly, these compounds were not formulated for cell permeation, which is required for bona fide RNA interference (RNAi). We showed that these "naked" siRNAs suppress neovascularization in mice not via RNAi but via sequence-independent activation of cell surface Toll-like receptor-3 (TLR3). Here, we demonstrate that noninternalized siRNAs induce retinal degeneration in mice by activating surface TLR3 on retinal pigmented epithelial cells. Cholesterol conjugated siRNAs capable of cell permeation and triggering RNAi also induce the same phenotype. Retinal degeneration was not observed after treatment with siRNAs shorter than 21-nts. Other cytosolic dsRNA sensors are not critical to this response. TLR3 activation triggers caspase-3-mediated apoptotic death of the retinal pigment epithelium (RPE) via nuclear translocation of interferon regulatory factor-3. While this unexpected adverse effect of siRNAs has implications for future clinical trials, these findings also introduce a new preclinical model of geographic atrophy (GA), a late stage of dry AMD that causes blindness in millions worldwide.
C1 [Kleinman, Mark E.; Kaneko, Hiroki; Cho, Won Gil; Dridi, Sami; Fowler, Benjamin J.; Blandford, Alexander D.; Albuquerque, Romulo J. C.; Hirano, Yoshio; Tarallo, Valeria; Gelfand, Bradley D.; Bogdanovich, Sasha; Baffi, Judit Z.; Ambati, Jayakrishna] Univ Kentucky, Dept Ophthalmol & Visual Sci, Lexington, KY 40536 USA.
   [Cho, Won Gil] Yonsei Univ, Dept Anat, Wonju Coll Med, Wonju, South Korea.
   [Terasaki, Hiroko] Nagoya Univ, Grad Sch Med, Dept Ophthalmol, Nagoya, Aichi 4648601, Japan.
   [Kondo, Mineo] Mie Univ, Grad Sch Med, Dept Ophthalmol, Tsu, Mie 514, Japan.
   [Fujita, Takashi] Kyoto Univ, Inst Virus Res, Dept Mol Genet, Kyoto 606, Japan.
   [Fujita, Takashi] Kyoto Univ, Grad Sch Biostudies, Kyoto, Japan.
   [Ambati, Balamurali K.] Univ Utah, Sch Med, Moran Eye Ctr, Dept Ophthalmol & Visual Sci, Salt Lake City, UT USA.
   [Ambati, Balamurali K.] Vet Affairs Salt Lake City Healthcare Syst, Dept Ophthalmol, Salt Lake City, UT USA.
   [Ambati, Jayakrishna] Univ Kentucky, Dept Physiol, Lexington, KY 40536 USA.
C3 University of Kentucky; Yonsei University; Nagoya University; Mie
   University; Kyoto University; Kyoto University; Utah System of Higher
   Education; University of Utah; US Department of Veterans Affairs;
   University of Kentucky
RP Ambati, J (通讯作者)，Univ Kentucky, Dept Ophthalmol & Visual Sci, 740 S Limestone St,Ste E302, Lexington, KY 40536 USA.
EM jamba2@email.uky.edu
RI Dridi, Sami/Q-8207-2019; Fowler, Benjamin/F-4987-2012; Kaneko,
   Hiroki/O-7695-2015; Gelfand, Brad/L-3926-2019; Terasaki,
   Hiroko/M-5054-2014; Kaneko, Hiroki/AHA-2461-2022
OI Kaneko, Hiroki/0000-0003-0731-6465; Kaneko, Hiroki/0000-0003-0731-6465;
   Tarallo, Valeria/0000-0002-6920-4402; Hirano, Yoshio/0000-0002-9173-0839
FU National Eye Institute/National Institutes of Health (NIH) [R01EY018350,
   R01EY018836, R01EY020672, R21EY019778, RC1EY020442]; Doris Duke
   Distinguished Clinical Scientist Award; Burroughs Wellcome Fund Clinical
   Scientist Award in Translational Research; Dr E. Vernon Smith and Eloise
   C. Smith Macular Degeneration Endowed Chair; Research to Prevent
   Blindness (RPB); NIH [K08EY021757, K08EY021521, T32HL091812,
   R01EY017182, R01EY017950]; American Health Assistance Foundation;
   University of Kentucky; International Retinal Research Foundation; VA
   Merit Award; Department of Defense; Grants-in-Aid for Scientific
   Research [23390401, 23592603] Funding Source: KAKEN; NATIONAL CENTER FOR
   ADVANCING TRANSLATIONAL SCIENCES [TL1TR000115, UL1TR001998, UL1TR000117]
   Funding Source: NIH RePORTER; NATIONAL CENTER FOR RESEARCH RESOURCES
   [TL1RR033172, UL1RR033173] Funding Source: NIH RePORTER; NATIONAL EYE
   INSTITUTE [RC1EY020442, R01EY022238, R21EY019778, R01EY018836,
   P30EY014800, R01EY018350, R01EY020672, K08EY021521, K08EY021757,
   R01EY017950, R01EY017182] Funding Source: NIH RePORTER; NATIONAL HEART,
   LUNG, AND BLOOD INSTITUTE [T32HL091812] Funding Source: NIH RePORTER
FX We thank R. King, L. Xu, M. McConnell, C. Payne, G.R. Pattison, D.
   Robertson, and G. Botzet for technical assistance, and R. Mohan, P.A.
   Pearson, A.M. Rao, G.S. Rao, K. Ambati, and B. Savage for discussions.
   J.A. was supported by National Eye Institute/National Institutes of
   Health (NIH) grants R01EY018350, R01EY018836, R01EY020672, R21EY019778,
   RC1EY020442, the Doris Duke Distinguished Clinical Scientist Award, the
   Burroughs Wellcome Fund Clinical Scientist Award in Translational
   Research, the Dr E. Vernon Smith and Eloise C. Smith Macular
   Degeneration Endowed Chair, the Senior Scientist Investigator Award
   [Research to Prevent Blindness (RPB)], and a departmental unrestricted
   grant from the RPB; M.E.K. by NIH K08EY021757 and Foundation Fighting
   Blindness; J.Z.B. by NIH K08EY021521 and American Health Assistance
   Foundation; M.E.K. and J.Z.B. by University of Kentucky Physician
   Scientist Awards and International Retinal Research Foundation; S.B. and
   B.J.F. by NIH T32HL091812; B.K.A. by NIH R01EY017182, R01EY017950, VA
   Merit Award and Department of Defense; J.A. is named as an inventor on a
   patent application filed by the University of Kentucky on ultrashort
   siRNAs as TLR3 antagonists.
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NR 35
TC 73
Z9 81
U1 0
U2 16
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JAN
PY 2012
VL 20
IS 1
BP 101
EP 108
DI 10.1038/mt.2011.212
PG 8
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 875HV
UT WOS:000299021900016
PM 21988875
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Kowluru, RA
   Zhong, Q
AF Kowluru, Renu A.
   Zhong, Qing
TI Beyond AREDS: Is There a Place for Antioxidant Therapy in the
   Prevention/Treatment of Eye Disease?
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; ENDOTHELIAL GROWTH-FACTOR; EXPERIMENTAL
   DIABETIC-RETINOPATHY; MITOCHONDRIAL-DNA DAMAGE; CAPILLARY CELL-DEATH;
   ALPHA-LIPOIC ACID; PROTEIN-KINASE-C; MACULAR DEGENERATION; NITRIC-OXIDE;
   VITAMIN-C
AB Age-related macular degeneration (AMD), the major cause of blindness in adults (65 years of age and older), and diabetic retinopathy, the major cause of blindness in working adults, are chronic, progressive diseases with multifaceted etiologies that are not fully understood. Progression and lack of treatment of both diseases may lead to the advanced stage with neovascularization. Although the detailed cellular mechanisms leading to the development of AMD and diabetic retinopathy remain elusive, oxidative damage to the retina and its pigment epithelium are considered to be involved. Clinical studies have shown that the progression of AMD can be slowed down by nutritional antioxidants, but trials with antioxidants for diabetic retinopathy (very limited in number) have been inconclusive. Long-term administration of the AREDS antioxidants, the same nutritional antioxidants that have been demonstrated to slow the progression of AMD, have yielded exciting results in preventing the pathogenesis of retinopathy in diabetic rodents. These results suggest the merit of testing the AREDS antioxidants in a clinical trial to prevent the development and/or progression of diabetic retinopathy, with the possibility of reducing the impact of this common vision-threatening disease. (Invest Ophthalmol Vis Sci. 2011;52:8665-8671) DOI: 10.1167/iovs.10-6768
C1 [Kowluru, Renu A.; Zhong, Qing] Wayne State Univ, Kresge Eye Inst, Detroit, MI 48201 USA.
C3 Wayne State University
RP Kowluru, RA (通讯作者)，Wayne State Univ, Kresge Eye Inst, Detroit, MI 48201 USA.
EM rkowluru@med.wayne.edu
FU National Institutes of Health; Thomas Foundation
FX Supported by grants from the National Institutes of Health and The
   Thomas Foundation.
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NR 100
TC 35
Z9 40
U1 0
U2 8
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD NOV
PY 2011
VL 52
IS 12
BP 8665
EP 8671
DI 10.1167/iovs.10-6768
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 844PW
UT WOS:000296760700016
PM 22065212
OA Green Published
DA 2022-11-30
ER

PT J
AU Sadda, SR
   Liakopoulos, S
   Keane, PA
   Ongchin, SC
   Msutta, S
   Chang, KT
   Walsh, AC
AF Sadda, Srinivas R.
   Liakopoulos, Sandra
   Keane, Pearse A.
   Ongchin, Sharel C.
   Msutta, Sandeep
   Chang, Karen T.
   Walsh, Alexander C.
TI Relationship between angiographic and optical coherence tomographic
   (OCT) parameters for quantifying choroidal neovascular lesions
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Optical coherence tomography; Fluorescein angiography; Quantitative
   image analysis; Age-related macular degeneration; Choroidal
   neovascularization
ID RETINAL ANGIOMATOUS PROLIFERATION; FUNDUS FLUORESCEIN ANGIOGRAPHY;
   MACULAR DEGENERATION; QUANTITATIVE SUBANALYSIS; PHOTODYNAMIC THERAPY;
   RANIBIZUMAB; MEMBRANES
AB To correlate the volume of various spaces on optical coherence tomography (OCT) with fluorescein angiographic (FA) parameters in neovascular age-related macular degeneration (AMD).
   Sixty-five consecutive cases of active subfoveal choroidal neovascularization (CNV) associated with AMD were retrospectively collected. Area and greatest linear dimension of CNV lesion components were calculated on FA. Corresponding StratusOCT image sets were analyzed using custom software (termed OCTOR), which allows manual measurement of the volume of the neurosensory retina, subretinal fluid, subretinal tissue, and pigment epithelial detachment (PED).
   Area of occult CNV on FA correlated with PED (R = 0.62) and subretinal fluid (R = 0.28) volume and negatively with subretinal tissue volume (R = -0.26) on OCT. Area of classic CNV on FA correlated with subretinal tissue (R = 0.60) and retinal (R = 0.38) volume on OCT. Automated StratusOCT output values showed poorer correlations than manually calculated OCTOR values.
   OCT features of CNV lesions as measured by manual quantitative subanalysis correlate better with angiographic parameters than values provided by the automated StratusOCT analysis. These measures may improve our understanding of the morphologic effects of CNV lesions and may facilitate the development of a hybrid FA and OCT-based classification system for future clinical trials, which more fully characterizes CNV lesions.
C1 [Sadda, Srinivas R.] Doheny Eye Inst DEI 3623, Los Angeles, CA 90033 USA.
   [Sadda, Srinivas R.; Liakopoulos, Sandra; Keane, Pearse A.; Ongchin, Sharel C.; Msutta, Sandeep; Chang, Karen T.; Walsh, Alexander C.] Univ So Calif, Keck Sch Med, Doheny Eye Inst, Doheny Image Reading Ctr, Los Angeles, CA 90033 USA.
   [Liakopoulos, Sandra] Univ Cologne, Ctr Ophthalmol, Dept Vitreoretinal Surg, Cologne, Germany.
C3 Doheny Eye Institute; Doheny Eye Institute; University of Southern
   California; University of Cologne
RP Sadda, SR (通讯作者)，Doheny Eye Inst DEI 3623, 1450 San Pablo St, Los Angeles, CA 90033 USA.
EM sadda@usc.edu
RI Keane, Pearse/AAE-5709-2019; Keane, Pearse A/H-1860-2011
OI Keane, Pearse/0000-0002-9239-745X; 
FU NIH [EY03040]; NEI [R01 EY014375]; National Institute for Health
   Research [CL-2010-18-004] Funding Source: researchfish; NATIONAL EYE
   INSTITUTE [R01EY014375, P30EY003040] Funding Source: NIH RePORTER
FX This study was supported in part by NIH Grant EY03040 and NEI Grant R01
   EY014375.
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NR 18
TC 24
Z9 24
U1 0
U2 3
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 FEB
PY 2010
VL 248
IS 2
BP 175
EP 184
DI 10.1007/s00417-009-1193-4
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 540EF
UT WOS:000273313100004
PM 19760223
DA 2022-11-30
ER

PT J
AU Perkins, SJ
   Okemefuna, AI
   Nan, R
   Li, KY
   Bonner, A
AF Perkins, Stephen J.
   Okemefuna, Azubuike I.
   Nan, Ruodan
   Li, Keying
   Bonner, Alexandra
TI Constrained solution scattering modelling of human antibodies and
   complement proteins reveals novel biological insights
SO JOURNAL OF THE ROYAL SOCIETY INTERFACE
LA English
DT Review
DE immunoglobulin A; complement factor H; analytical ultracentrifugation;
   constrained modelling; neutron scattering; X-ray scattering
ID X-RAY-SCATTERING; EXTENDED SOLUTION STRUCTURE; BACK SOLUTION STRUCTURE;
   FACTOR-H; ANALYTICAL ULTRACENTRIFUGATION; NEUTRON-SCATTERING;
   HYDRODYNAMIC PROPERTIES; SECRETORY COMPONENT; DIMERIC IGA1; C3D
AB X-ray and neutron-scattering techniques characterize proteins in solution and complement high-resolution structural studies. They are useful when either a large protein cannot be crystallized, in which case scattering yields a solution structure, or a crystal structure has been determined and requires validation in solution. These solution structures are determined by the application of constrained modelling methods based on known subunit structures. First, an appropriate starting model is generated. Next, its conformation is randomized to generate thousands of models for trial-and-error fits. Comparison with the experimental data identifies a small family of best-fit models. Finally, their significance for biological function is assessed. We illustrate this in application to structure determinations for secretory immunoglobulin A, the most prevalent antibody in the human body and a first line of defence in mucosal immunity. We also discuss the applications to the large multi-domain proteins of the complement system, most notably its major regulator factor H, which is important in age-related macular degeneration and renal diseases. We discuss the importance of complementary data from analytical ultracentrifugation, and structural studies of protein-protein complexes. We conclude that constrained scattering modelling makes useful contributions to our understanding of antibody and complement structure and function.
C1 [Perkins, Stephen J.; Okemefuna, Azubuike I.; Nan, Ruodan; Li, Keying; Bonner, Alexandra] UCL, Dept Struct & Mol Biol, London WC1E 6BT, England.
C3 University of London; University College London
RP Perkins, SJ (通讯作者)，UCL, Dept Struct & Mol Biol, Darwin Bldg,Gower St, London WC1E 6BT, England.
EM s.perkins@medsch.ucl.ac.uk
FU Wellcome Trust; BBSRC; MRC [G0801724] Funding Source: UKRI; Medical
   Research Council [G0801724] Funding Source: researchfish
FX We thank the Wellcome Trust and BBSRC for support. We are particularly
   grateful to our IgA colleagues Dr Blaise Corthesy, Dr Jennifer M. Woof
   and Prof. Michael A. Kerr, and our factor H colleagues Dr Imre Lengyel,
   Dr Robert B. Sim and Prof. David Gordon for their support. We also thank
   Jayesh Gor at UCL, Dr Theyencheri Narayanan, Dr Stephanie Finet, Dr
   Pierre Panine and Dr Anuj Shukla at ESRF and Dr Richard K. Heenan and Dr
   Stephen M. King at ISIS for instrumental support, without which these
   projects would not have been completed.
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NR 49
TC 35
Z9 35
U1 0
U2 6
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 1742-5689
EI 1742-5662
J9 J R SOC INTERFACE
JI J. R. Soc. Interface
PD OCT 6
PY 2009
VL 6
SU 5
BP S679
EP S696
DI 10.1098/rsif.2009.0164.focus
PG 18
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 494PQ
UT WOS:000269826500013
PM 19605402
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Guaiquil, V
   Swendeman, S
   Yoshida, T
   Chavala, S
   Campochiaro, PA
   Blobel, CP
AF Guaiquil, Victor
   Swendeman, Steven
   Yoshida, Tsunehiko
   Chavala, Sai
   Campochiaro, Peter A.
   Blobel, Carl P.
TI ADAM9 Is Involved in Pathological Retinal Neovascularization
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID METALLOPROTEASE-DISINTEGRIN MDC9; GROWTH-FACTOR-RECEPTOR;
   PROSTATE-CANCER CELLS; OCULAR NEOVASCULARIZATION; RETINOPATHY;
   ECTODOMAIN; ANGIOGENESIS; VASCULATURE; EXPRESSION; LIGANDS
AB Pathological ocular neovascularization, caused by diabetic retinopathy, age-related macular degeneration, or retinopathy of prematurity, is a leading cause of blindness, yet much remains to be learned about its underlying causes. Here we used oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) to assess the contribution of the metalloprotease-disintegrin ADAM9 to ocular neovascularization in mice. Pathological neovascularization in both the OIR and CNV models was significantly reduced in Adam9(-/-) mice compared to wild-type controls. In addition, the level of ADAM9 expression was strongly increased in endothelial cells in pathological vascular tufts in the OIR model. Moreover, tumor growth from heterotopically injected B16F0 melanoma cells was reduced in Adam9(-/-) mice compared to controls. In cell-based assays, the overexpression of ADAM9 enhanced the ectodomain shedding of EphB4, Tie-2, Flk-1, CD40, VCAM, and VE-cadherin, so the enhanced expression of ADAM9 could potentially affect pathological neovascularization by increasing the shedding of these and other membrane proteins from endothelial cells. Finally, we provide the first evidence for the upregulation of ADAM9-dependent shedding by reactive oxygen species, which in turn are known to play a critical role in OIR. Collectively, these results suggest that ADAM9 could be an attractive target for the prevention of proliferative retinopathies, CNV, and cancer.
C1 [Guaiquil, Victor; Swendeman, Steven; Blobel, Carl P.] Hosp Special Surg, Arthrit & Tissue Degenerat Program, New York, NY 10021 USA.
   [Blobel, Carl P.] Cornell Univ, Weill Med Coll, Dept Physiol & Med, New York, NY 10021 USA.
   [Blobel, Carl P.] Cornell Univ, Weill Med Coll, Dept Biophys, New York, NY 10021 USA.
   [Blobel, Carl P.] Cornell Univ, Weill Med Coll, Dept Syst Biol, New York, NY 10021 USA.
   [Yoshida, Tsunehiko; Campochiaro, Peter A.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
   [Chavala, Sai] Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA.
C3 Cornell University; Cornell University; Cornell University; Johns
   Hopkins University; Johns Hopkins Medicine; Duke University
RP Blobel, CP (通讯作者)，Hosp Special Surg, Arthrit & Tissue Degenerat Program, Caspary Res Bldg,Rm 426,535 E 70th St, New York, NY 10021 USA.
EM blobelc@hss.edu
FU National Institutes of Health; Eye Institute [EY15759, EY12609];
   NATIONAL EYE INSTITUTE [K08EY021171, R01EY015719, R01EY012609] Funding
   Source: NIH RePORTER
FX This work was supported by National Institutes of Health grants from the
   Eye Institute to C. P. B. (grant EY15759) and to P. C. ( grant
   EY12609).; We thank Viktoriya Nikolenko and Joshua Namm for excellent
   technical assistance and Shahin Rafii for providing access to his
   confocal microscope.
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NR 30
TC 71
Z9 73
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD MAY 15
PY 2009
VL 29
IS 10
BP 2694
EP 2703
DI 10.1128/MCB.01460-08
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA 439ZD
UT WOS:000265665900017
PM 19273593
OA Green Published
DA 2022-11-30
ER

PT J
AU Zhou, JL
   Jang, YP
   Chang, S
   Sparrow, JR
AF Zhou, Jilin
   Jang, Young P.
   Chang, Stanley
   Sparrow, Janet R.
TI OT-674 suppresses photooxidative processes initiated by an RPE
   lipofuscin fluorophore
SO PHOTOCHEMISTRY AND PHOTOBIOLOGY
LA English
DT Article
ID PIGMENT EPITHELIAL-CELLS; AGE-RELATED MACULOPATHY; OXIDANT-INDUCED
   APOPTOSIS; MITOCHONDRIAL-DNA DAMAGE; LIGHT-INDUCED DAMAGE; MACULAR
   DEGENERATION; BLUE-LIGHT; FUNDUS AUTOFLUORESCENCE; GEOGRAPHIC ATROPHY;
   OXIDATIVE STRESS
AB The pathological processes involved in age-related macular degeneration (AMD) include retinal pigment epithelial (RPE) cell degeneration; oxidative mechanisms likely contribute to the demise of these cells. Indeed, RPE cells may be particularly susceptible to photooxidative mechanisms since they accumulate retinoid-derived photoreactive compounds that constitute the lipofuscin of the cell. Thus we undertook to test the capacity of OT-674, the reduction product (Tempol-H) of the nitroxide Tempol, to suppress photooxidative processes initiated by the RPE lipofuscin fluorophore A2E. Accordingly, when ARPE-19 cells that had accumulated A2E were irradiated at 430 nm, pretreatment with OT-674 (0.01-10 mm) was found to confer a resistance to cell death. Monitoring by quantitative HPLC also showed that OT-674 reduced A2E photooxidation in a cell-free system. Moreover, when presented with a singlet oxygen generator, OT-674 served as a quencher of singlet oxygen that was more effective than Trolox and alpha-tocopherol. We conclude that OT-674 is a potent antioxidant that suppresses photooxidative processes generated in cultured RPE cells by the lipofuscin fluorophore A2E. As oxidative damage to RPE cells is considered to be a risk factor for AMD, antioxidant therapy with OT-674 may serve a protective role.
C1 [Zhou, Jilin; Jang, Young P.; Chang, Stanley; Sparrow, Janet R.] Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA.
C3 Columbia University
RP Sparrow, JR (通讯作者)，Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA.
EM jrs88@columbia.edu
RI Jang, Young Pyo/AAJ-8782-2020; Chang, Stanley/AAL-2741-2021
OI Jang, Young Pyo/0000-0001-5865-9228; 
FU NEI NIH HHS [R01 EY012951-11, R01 EY012951, EY 12951] Funding Source:
   Medline; NATIONAL EYE INSTITUTE [R01EY012951] Funding Source: NIH
   RePORTER
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NR 65
TC 13
Z9 14
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 JAN-FEB
PY 2008
VL 84
IS 1
BP 75
EP 80
DI 10.1111/j.1751-1097.2007.00205.x
PG 6
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 253GO
UT WOS:000252506900012
PM 18173705
DA 2022-11-30
ER

PT J
AU Tatar, O
   Adam, A
   Shinoda, K
   Stalmans, P
   Eckardt, C
   Luke, M
   Bartz-Schmidt, KU
   Grisanti, S
AF Tatar, Olcay
   Adam, Annemarie
   Shinoda, Kei
   Stalmans, Peter
   Eckardt, Claus
   Lueke, Matthias
   Bartz-Schmidt, Karl Ulrich
   Grisanti, Salvatore
TI Expression of VEGF and PEDF in choroidal neovascular membranes following
   verteporfin photodynamic therapy
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID EPITHELIUM-DERIVED FACTOR; ENDOTHELIAL GROWTH-FACTOR; RETINAL-PIGMENT
   EPITHELIUM; MACULAR DEGENERATION; DOWN-REGULATION; CLINICAL-TRIAL;
   VISUAL-ACUITY; GENE-TRANSFER; HUMAN EYES; ANGIOGENESIS
AB PURPOSE: To examine the impact of photodynamic therapy (PDT) on pigment epithelium derived factor (PEDF) expression in human choroidal neovascularization (CNV) membranes with regard to vascular endothelial growth factor (VEGF) expression.
   DESIGN: Interventional case series.
   METHODS: Retrospective review of interventional case series of 42 patients (42 eyes) who underwent removal of CNV. CNV was secondary to age-related macular degeneration (AMD) in all cases. Fifteen patients were treated with PDT, 3 to 246 days before surgery. CNV were stained for CD34, CD105, cytokeratin 18, VEGF, and PEDF. Twenty-seven CNV without previous treatment were used as control.
   RESULTS: Specimens without pretreatment disclosed varying degrees of vascularization, VEGF, and PEDF expression by different cells. Specimens treated by PDT, three days previously showed mostly occluded vessels lined with damaged endothelial cells (EC). In contrast, specimens excised at later time points after PDT were highly vascularized with healthy EC. This chronology was associated with an impressive VEGF immunoreactivity increased considerably in retinal pigment epithelial cells as well as significantly reduced PEDF expression in EC and stroma.
   CONCLUSIONS: PDT induces a selective vascular dam, age in CNV. The effectiveness of PDT, however, seems to be jeopardized by a rebound effect initiated by an enhanced VEGF and reduced PEDF expression in CNV.
C1 Univ Tubingen, Dept Ophthalmol, Div Vitreoretinal Surg, Univ Eye Clin,Ctr Ophthalmol, D-72076 Tubingen, Germany.
   Univ Tubingen, Dept Pathol, D-72076 Tubingen, Germany.
   Natl Inst Sensory Organs, Lab Visual Physiol, Tokyo, Japan.
   UZ St Rafael, Dept Ophthalmol, Louvain, Belgium.
   Stadt Kliniken, Augenklin, Frankfurt, Germany.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University
   Hospital; Eberhard Karls University of Tubingen; Eberhard Karls
   University Hospital; University of Hamburg; University Medical Center
   Hamburg-Eppendorf
RP Grisanti, S (通讯作者)，Univ Tubingen, Dept Ophthalmol, Div Vitreoretinal Surg, Univ Eye Clin,Ctr Ophthalmol, Schleichstr 12-15, D-72076 Tubingen, Germany.
EM Salvatore.Grisanti@med.uni-tuebingen.de
RI Shinoda, Kei/ABC-7993-2020
OI Shinoda, Kei/0000-0002-1543-9345
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NR 55
TC 79
Z9 85
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
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD JUL
PY 2006
VL 142
IS 1
BP 95
EP 104
DI 10.1016/j.ajo.2006.01.085
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 064HF
UT WOS:000239079100013
PM 16815256
DA 2022-11-30
ER

PT J
AU Ahamed, W
   Yu, RMC
   Pan, Y
   Iwata, T
   Barathi, VA
   Wey, YS
   Tun, SBB
   Qiu, BY
   Tan, A
   Wang, XM
   Cheung, CMG
   Wong, TY
   Yanagi, Y
AF Ahamed, Waseem
   Yu, Richard Ming Chuan
   Pan, Yang
   Iwata, Takeshi
   Barathi, Veluchamy Amutha
   Wey, Yeo Sia
   Tun, Sai Bo Bo
   Qiu, Beiying
   Tan, Alison
   Wang, Xiaomeng
   Cheung, Chui Ming Gemmy
   Wong, Tien Yin
   Yanagi, Yasuo
TI HTRA1 Regulates Subclinical Inflammation and Activates Proangiogenic
   Response in the Retina and Choroid
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE HtrA1 mice; age-related macular degeneration; polypoidal choroidal
   neovascularization; RNA-sequencing; subclinical inflammation;
   proangiogenic response; KEGG & Reactome pathways; immune system process
   GO-terms
ID SUBRETINAL MICROGLIA; INCREASED EXPRESSION; PIGMENT EPITHELIUM;
   SERINE-PROTEASE; GENE; ACCUMULATION; MOUSE; CELLS; MICE;
   NEOVASCULARIZATION
AB High-temperature requirement A1 (HtrA1) has been identified as a disease-susceptibility gene for age-related macular degeneration (AMD) including polypoidal choroidal neovasculopathy (PCV). We characterized the underlying phenotypic changes of transgenic (Tg) mice expressing ubiquitous CAG promoter (CAG-HtrA1 Tg). In vivo imaging modalities and histopathology were performed to investigate the possible neovascularization, drusen formation, and infiltration of macrophages. Subretinal white material deposition and scattered white-yellowish retinal foci were detected on CFP [(Tg-33% (20/60) and wild-type (WT)-7% (1/15), p < 0.05]. In 40% (4/10) of the CAG-HtrA1 Tg retina, ICGA showed punctate hyperfluorescent spots. There was no leakage on FFA and OCTA failed to confirm vascular flow signals from the subretinal materials. Increased macrophages and RPE cell migrations were noted from histopathological sections. Monocyte subpopulations were increased in peripheral blood in the CAG-HtrA1 Tg mice (p < 0.05). Laser induced CNV in the CAG-HtrA1 Tg mice and showed increased leakage from CNV compared to WT mice (p < 0.05). Finally, choroidal explants of the old CAG-HtrA1 Tg mice demonstrated an increased area of sprouting (p < 0.05). Signs of subclinical inflammation was observed in CAG-HtrA1 Tg mice. Such subclinical inflammation may have resulted in increased RPE cell activation and angiogenic potential.
C1 [Ahamed, Waseem; Yu, Richard Ming Chuan; Barathi, Veluchamy Amutha; Wey, Yeo Sia; Tun, Sai Bo Bo; Qiu, Beiying; Tan, Alison; Wang, Xiaomeng; Cheung, Chui Ming Gemmy; Wong, Tien Yin; Yanagi, Yasuo] Singapore Eye Res Inst, Singapore Natl Eye Ctr, 11 Third Hosp Ave, Singapore 168751, Singapore.
   [Pan, Yang; Iwata, Takeshi] Natl Hosp Org Tokyo Med Ctr, Natl Inst Sensory Organs, Mol & Cellular Biol Div, Tokyo 1528902, Japan.
   [Barathi, Veluchamy Amutha; Qiu, Beiying; Tan, Alison; Wang, Xiaomeng; Cheung, Chui Ming Gemmy; Wong, Tien Yin; Yanagi, Yasuo] Natl Univ Singapore, Acad Clin Program, Duke NUS Med Sch, Singapore 169857, Singapore.
   [Wang, Xiaomeng] ASTAR, Inst Mol & Cell Biol, Singapore 138673, Singapore.
C3 National University of Singapore; Singapore National Eye Center;
   National University of Singapore; Agency for Science Technology &
   Research (A*STAR); A*STAR - Institute of Molecular & Cell Biology (IMCB)
RP Yanagi, Y (通讯作者)，Singapore Eye Res Inst, Singapore Natl Eye Ctr, 11 Third Hosp Ave, Singapore 168751, Singapore.; Yanagi, Y (通讯作者)，Natl Univ Singapore, Acad Clin Program, Duke NUS Med Sch, Singapore 169857, Singapore.
EM yasuo.yanagi@snec.com.sg
RI ; TUN, SAI BO BO/O-1085-2018
OI Pan, Yang/0000-0001-7673-2599; Barathi, Veluchamy
   Amutha/0000-0002-6477-9784; TUN, SAI BO BO/0000-0002-2013-8379
FU Biomedical Research Council Singapore [SPF2014/002]; National Medical
   Research Council Singapore Large Collaborative Grant TAAP
   [NMRC/OFLCG/004/2018]
FX Supported by Biomedical Research Council Singapore Grant: SPF2014/002;
   National Medical Research Council Singapore Large Collaborative Grant
   TAAP (NMRC/OFLCG/004/2018). The funding organization had no role in the
   design or conduct of this research.
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NR 64
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 SEP
PY 2022
VL 23
IS 18
AR 10206
DI 10.3390/ijms231810206
PG 20
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA 4V4TX
UT WOS:000859472000001
PM 36142120
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Schafer, N
   Rasras, A
   Ormenisan, DM
   Amslinger, S
   Enzmann, V
   Jagle, H
   Pauly, D
AF Schaefer, Nicole
   Rasras, Anas
   Ormenisan, Delia M.
   Amslinger, Sabine
   Enzmann, Volker
   Jaegle, Herbert
   Pauly, Diana
TI Complement Factor H-Related 3 Enhanced Inflammation and Complement
   Activation in Human RPE Cells
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Article
DE AMD; complement activation; complosome; FHR-3; inflammation; oxidative
   stress epitopes; RETC-2; RPE cells FHR-3 alters RPE cell complosome
ID PIGMENT EPITHELIAL-CELLS; GENOME-WIDE ASSOCIATION; RETINAL-PIGMENT;
   OXIDATIVE STRESS; INTRACELLULAR COMPLEMENT; MACULAR DEGENERATION;
   SECRETION; BINDS; ACCUMULATION; IL-1-BETA
AB Complement Factor H-Related 3 (FHR-3) is a major regulator of the complement system, which is associated with different diseases, such as age-related macular degeneration (AMD). However, the non-canonical local, cellular functions of FHR-3 remained poorly understood. Here, we report that FHR-3 bound to oxidative stress epitopes and competed with FH for interaction. Furthermore, FHR-3 was internalized by viable RPE cells and modulated time-dependently complement component (C3, FB) and receptor (C3aR, CR3) expression of human RPE cells. Independently of any external blood-derived proteins, complement activation products were detected. Anaphylatoxin C3a was visualized in treated cells and showed a translocation from the cytoplasm to the cell membrane after FHR-3 exposure. Subsequently, FHR-3 induced a RPE cell dependent pro-inflammatory microenvironment. Inflammasome NLRP3 activation and pro-inflammatory cytokine secretion of IL-1ss, IL-18, IL-6 and TNF-alpha were induced after FHR-3-RPE interaction. Our previously published monoclonal anti-FHR-3 antibody, which was chimerized to reduce immunogenicity, RETC-2-ximab, ameliorated the effect of FHR-3 on ARPE-19 cells. Our studies suggest FHR-3 as an exogenous trigger molecule for the RPE cell "complosome" and as a putative target for a therapeutic approach for associated degenerative diseases.
C1 [Schaefer, Nicole; Ormenisan, Delia M.; Jaegle, Herbert; Pauly, Diana] Univ Hosp Regensburg, Dept Ophthalmol, Regensburg, Germany.
   [Schaefer, Nicole] Univ Regensburg, Ctr Med Biotechnol ZMB, Dept Orthoped Surg Expt Orthopaed, Regensburg, Germany.
   [Rasras, Anas] Al Balqa Appl Univ, Chem Dept, Al Salt, Jordan.
   [Rasras, Anas; Amslinger, Sabine] Univ Regensburg, Inst Organ Chem, Regensburg, Germany.
   [Enzmann, Volker] Univ Bern, Dept Ophthalmol, Univ Hosp Bern, Bern, Switzerland.
   [Enzmann, Volker] Univ Bern, Dept Biomed Res, Bern, Switzerland.
   [Pauly, Diana] Philipps Univ Marburg, Expt Ophthalmol, Marburg, Germany.
C3 University of Regensburg; University of Regensburg; Al-Balqa Applied
   University; University of Regensburg; 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, Regensburg, Germany.; Pauly, D (通讯作者)，Philipps Univ Marburg, Expt Ophthalmol, Marburg, Germany.
EM diana.pauly@uni-marburg.de
RI Jägle, Herbert/GPP-2945-2022
OI Rasras, Anas/0000-0003-4203-7031
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NR 63
TC 5
Z9 5
U1 1
U2 5
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 1664-3224
J9 FRONT IMMUNOL
JI Front. Immunol.
PD NOV 8
PY 2021
VL 12
AR 769242
DI 10.3389/fimmu.2021.769242
PG 16
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA XB1BE
UT WOS:000721069300001
PM 34819935
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Neelam, K
   Dey, S
   Sim, R
   Lee, J
   Eong, KGA
AF Neelam, Kumari
   Dey, Sonali
   Sim, Ralene
   Lee, Jason
   Au Eong, Kah-Guan
TI Fructus lycii: A Natural Dietary Supplement for Amelioration of Retinal
   Diseases
SO NUTRIENTS
LA English
DT Review
DE Fructus lycii; carotenoids; antioxidants; age-related macular
   degeneration; diabetic retinopathy; retinitis pigmentosa
ID TRADITIONAL CHINESE MEDICINE; GOJI BERRY EXTRACTS; BARBARUM
   POLYSACCHARIDES; OXIDATIVE STRESS; DIABETIC-RETINOPATHY; ANTIOXIDANT
   ACTIVITIES; PROBABLE INTERACTION; PIGMENT EPITHELIUM; TAURINE PREVENTS;
   ZEAXANTHIN
AB Fructus lycii (F. lycii) is an exotic "berry-type" fruit of the plant Lycium barbarum that is characterized by a complex mixture of bioactive compounds distinguished by their high antioxidant potential. F. lycii is used in traditional Chinese home cooking and in the Chinese Pharmacopeia as an aid to vision and longevity as well as a remedy for diabetes to balance "yin" and "yang" in the body for about two centuries. Although a myriad of bioactive compounds have been isolated from F. lycii, polysaccharides, carotenoids, flavonoids, and phenolics represent the key functional components of F. lycii. F. lycii has been shown to exhibit a wide range of biological activities in experimental settings including antioxidant, anti-inflammatory, antiapoptotic, and neuroprotective effects. Despite its medicinal role dating back to the eighteenth century in the Far East and robust evidence of beneficial effects on ocular health and retinal diseases originating mainly from studies in animal models, the role of F. lycii in the clinical management of retinal diseases is yet to be established. This article comprehensively reviews the literature germane to F. lycii and retinal diseases with particular emphasis on age-related macular degeneration, diabetic retinopathy, and retinitis pigmentosa, which are commonly seen in clinical practice.
C1 [Neelam, Kumari; Lee, Jason; Au Eong, Kah-Guan] Khoo Teck Puat Hosp, Dept Ophthalmol & Visual Sci, Singapore 768828, Singapore.
   [Neelam, Kumari] Singapore Eye Res Inst, Singapore 169856, Singapore.
   [Dey, Sonali; Sim, Ralene] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 119228, Singapore.
   [Au Eong, Kah-Guan] Farrer Pk Med Ctr, Int Eye Cataract Retina Ctr, Singapore 217562, Singapore.
C3 National University of Singapore; Singapore National Eye Center;
   National University of Singapore
RP Neelam, K (通讯作者)，Khoo Teck Puat Hosp, Dept Ophthalmol & Visual Sci, Singapore 768828, Singapore.; Neelam, K (通讯作者)，Singapore Eye Res Inst, Singapore 169856, Singapore.
EM kumari.neelam@ktph.com.sg; e0105134@u.nus.edu;
   ralene_sim1995@hotmail.com; lee.jason.ks@ktph.com.sg;
   aekg@eyecataractretina.com
FU Science-Translational and Applied Research [STAR19102]
FX This research was supported by Science-Translational and Applied
   Research (STAR19102).
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NR 114
TC 18
Z9 18
U1 13
U2 44
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2072-6643
J9 NUTRIENTS
JI Nutrients
PD JAN
PY 2021
VL 13
IS 1
AR 246
DI 10.3390/nu13010246
PG 25
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA PW4JN
UT WOS:000610637500001
PM 33467087
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Lundin, E
   Widen, SE
   Wahlqvist, M
   Anderzen-Carlsson, A
   Granberg, S
AF Lundin, Elin
   Widen, Stephen E.
   Wahlqvist, Moa
   Anderzen-Carlsson, Agneta
   Granberg, Sarah
TI Prevalence, diagnoses and rehabilitation services related to severe dual
   sensory loss (DSL) in older persons: a cross-sectional study based on
   medical records
SO INTERNATIONAL JOURNAL OF AUDIOLOGY
LA English
DT Article
DE 65 years and older; prevalence; rehabilitation services; severe dual
   sensory loss; diagnoses
ID HEARING IMPAIRMENT; VISION IMPAIRMENT; DEAFBLINDNESS; ASSOCIATION;
   DISTANCE; ADULTS; BLINDNESS; PEOPLE; IMPACT; CUES
AB Objective:To estimate the prevalence of severe dual sensory loss (DSL) among older persons (aged >= 65 years) in the Swedish population, to identify the diagnoses that cause severe DSL, and to identify rehabilitation services in which the participants have been involved. Design:A cross-sectional design was applied. Medical records from Audiological, Low Vision, and Vision clinics from two Swedish counties were used. Study sample:1257 adults, aged >= 65 years with severe hearing loss (HL) (>= 70 dB HL) were included, whereof 101 had decimal visual acuity <= 0.3. Results:Based on the population size in the two counties (>= 65 years, n = 127,638), the prevalence of severe DSL was approximately 0.08% in the population. Within the group having DSL (n = 101), 61% were women and 71% were aged >= 85 years. Common diagnoses were cataract and/or age-related macular degeneration (AMD) in combination with HL. The rehabilitation services offered were mainly hearing aids and various magnifiers. Conclusions:The study confirmed previous results, indicating that the prevalence of severe DSL increases with age and that sensorineural HL and cataract, AMD or glaucoma coexist. The identified rehabilitation services mainly focussed on either vision loss or HL but not on severe DSL as a complex health condition.
C1 [Lundin, Elin; Widen, Stephen E.; Granberg, Sarah] Orebro Univ, Sch Hlth Sci, Orebro, Sweden.
   [Lundin, Elin] Orebro Univ, Sch Successful Ageing, Orebro, Sweden.
   [Lundin, Elin; Widen, Stephen E.; Wahlqvist, Moa; Anderzen-Carlsson, Agneta; Granberg, Sarah] Orebro Univ, Swedish Inst Disabil Res, Orebro, Sweden.
   [Wahlqvist, Moa] Swedish Natl Resource Ctr Deafblindness, Lund, Sweden.
   [Wahlqvist, Moa; Granberg, Sarah] Orebro Univ, Fac Med & Hlth, Audiol Res Ctr, Orebro, Sweden.
   [Anderzen-Carlsson, Agneta] Orebro Univ, Fac Med & Hlth, Univ Hlth Care Res Ctr, Orebro, Sweden.
C3 Orebro University; Orebro University; Orebro University; Orebro
   University; Orebro University
RP Lundin, E (通讯作者)，Orebro Univ, Sch Hlth Sci, Orebro, Sweden.
EM elin.lundin@oru.se
RI Granberg, Sarah/ABH-4113-2020
OI Anderzen Carlsson, Agneta/0000-0001-7352-8234; Granberg,
   Sarah/0000-0002-2298-6806
FU Research School of Successful Ageing, Orebro University, Orebro, Sweden;
   Research Committee of Region Orebro County, Sweden
FX The study was funded by the Research School of Successful Ageing, Orebro
   University, Orebro, Sweden and the Research Committee of Region Orebro
   County, Sweden.
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NR 53
TC 2
Z9 2
U1 1
U2 7
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1499-2027
EI 1708-8186
J9 INT J AUDIOL
JI Int. J. Audiol.
PD DEC 1
PY 2020
VL 59
IS 12
BP 921
EP 929
DI 10.1080/14992027.2020.1783003
EA JUL 2020
PG 9
WC Audiology & Speech-Language Pathology; Otorhinolaryngology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Audiology & Speech-Language Pathology; Otorhinolaryngology
GA PA2NQ
UT WOS:000546281900001
PM 32628050
OA hybrid
DA 2022-11-30
ER

PT J
AU Nemoto, E
   Kojima, S
   Sugiyama, T
   Jin, D
   Takai, S
   Maeda, M
   Kohmoto, R
   Ueki, M
   Oku, H
   Ikeda, T
AF Nemoto, Emika
   Kojima, Shota
   Sugiyama, Tetsuya
   Jin, Denan
   Takai, Shinji
   Maeda, Michiko
   Kohmoto, Ryohsuke
   Ueki, Mari
   Oku, Hidehiro
   Ikeda, Tsunehiko
TI Effects of Regorafenib, a Multi-Kinase Inhibitor, on Conjunctival
   Scarring in a Canine Filtration Surgery Model in Comparison with
   Mitomycin-C
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE beagles; glaucoma; multi-kinase inhibitor; regorafenib; trabeculectomy
ID TRABECULECTOMY; 5-FLUOROURACIL; MYOFIBROBLAST; ACTIVATION; EXPRESSION;
   TGF-BETA-1; INFECTION; APOPTOSIS; ANGLE; BLEB
AB Regorafenib eye drops were developed for treating age-related macular degeneration. This study aimed to investigate the effects of this multi-kinase inhibitor on intraocular pressure (IOP), bleb formation, and conjunctival changes in a canine filtration surgery model. Glaucoma filtration surgery models were created in 24 eyes of 24 beagles. In experiment 1 (Ex 1), regorafenib eye drops (regorafenib group: n = 6) or a vehicle (control group, n = 6) were instilled twice daily for 4 weeks postoperatively. In experiment 2 (Ex 2), regorafenib eye drops were instilled as in Ex 1 (regorafenib group: n = 6) for 12 weeks while conventional intraoperative mitomycin-C (MMC) was utilized (MMC group: n = 6), In Ex 1, only the regorafenib group showed significant IOP reduction with a significantly higher bleb score. Subconjunctival area, collagen density, vessels, and cells showing proliferation and differentiation were lower in subconjunctival tissue in the regorafenib group. In Ex 2, no significant difference was found in IOP reduction and bleb formation between the regorafenib and MMC groups; bleb walls were significantly thicker and collagen density and vessels were higher in the regorafenib group; and no differences were observed in the above-mentioned cells. Thus, regorafenib might be a better alternative to MMC for creating thicker and less ischemic blebs in glaucoma filtration surgery.
C1 [Nemoto, Emika; Kojima, Shota; Sugiyama, Tetsuya; Maeda, Michiko; Kohmoto, Ryohsuke; Oku, Hidehiro; Ikeda, Tsunehiko] Osaka Med Coll, Dept Ophthalmol, Takatsuki, Osaka 5698686, Japan.
   [Jin, Denan; Takai, Shinji] Osaka Med Coll, Dept Innovat Med, Takatsuki, Osaka 5698686, Japan.
   [Ueki, Mari] NAGATA Eye Clin, Nara, Nara 6310844, Japan.
C3 Osaka Medical College; Osaka Medical College
RP Kojima, S (通讯作者)，Osaka Med Coll, Dept Ophthalmol, Takatsuki, Osaka 5698686, Japan.
EM emika0808@yahoo.co.jp; shota@osaka-med.ac.jp; tsugiyama@osaka-med.ac.jp;
   pha012@osaka-med.ac.jp; pha010@osaka-med.ac.jp; opt182@osaka-med.ac.jp;
   opt183@osaka-med.ac.jp; opt089@osaka-med.ac.jp; opt025@osaka-med.ac.jp;
   tikeda@osaka-med.ac.jp
OI Takai, Shinji/0000-0003-3963-3983; Oku, Hidehiro/0000-0003-4359-4219;
   KOJIMA, SHOTA/0000-0001-5388-926X
FU Japanese Ministry of Education [17K11496]
FX This research was funded by Japanese Ministry of Education Grant
   17K11496 (S.K.).
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NR 38
TC 0
Z9 0
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 JAN 1
PY 2020
VL 21
IS 1
AR 63
DI 10.3390/ijms21010063
PG 14
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA KO2KF
UT WOS:000515378000063
PM 31861830
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Nor, MNM
   Rupenthal, ID
   Green, CR
   Acosta, ML
AF Nor, Mohd Nasir Mat
   Rupenthal, Ilva D.
   Green, Colin R.
   Acosta, Monica L.
TI Connexin Hemichannel Block Using Orally Delivered Tonabersat Improves
   Outcomes in Animal Models of Retinal Disease
SO NEUROTHERAPEUTICS
LA English
DT Article
DE Macular degeneration; diabetic retinopathy; tonabersat; inflammasome;
   retina; choroid; Connexin43; inflammation
ID GAP-JUNCTION MODULATOR; MIMETIC PEPTIDE; NLRP3 INFLAMMASOME;
   SPINAL-CORD; CX43 HEMICHANNELS; DOUBLE-BLIND; MOUSE MODEL; CELL-DEATH;
   MIGRAINE; INJURY
AB Increased Connexin43 hemichannel opening is associated with inflammasome pathway activation and inflammation in a range of pathologies including ocular disorders, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). In this study, the effect on retinal function and morphology of clinically safe doses of orally delivered tonabersat, a small molecule connexin hemichannel blocker, was investigated in the light-damaged retina animal model of dry AMD and in a spontaneous rat model of DR. Clinical parameters (fundus imaging, optical coherence tomography (OCT), and electroretinography) and inflammatory markers (immunohistochemistry for Iba-1 microglial marker, astrocyte marker glial fibrillary acidic protein, and Connexin43 protein expression) were assessed. Tonabersat treatment reduced inflammation in the retina in parallel with preservation of retinal photoreceptor function when assessed up to 3 months post light damage in the dry AMD model. In the DR model, clinical signs, including the presence of aneurysms confirmed using Evans blue dye perfusion, were reduced after daily tonabersat treatment for 2 weeks. Inflammation was also reduced and retinal electrical function restored. Tonabersat regulates assembly of the inflammasome (NLRP3) through Connexin43 hemichannel block, with the potential to reduce inflammation, restore vascular integrity and improve anatomical along with some functional outcomes in retinal disease.
C1 [Nor, Mohd Nasir Mat; Acosta, Monica L.] Univ Auckland, Sch Optometry & Vis Sci, Auckland, New Zealand.
   [Nor, Mohd Nasir Mat; Rupenthal, Ilva D.; Green, Colin R.; Acosta, Monica L.] Univ Auckland, New Zealand Natl Eye Ctr, Auckland, New Zealand.
   [Nor, Mohd Nasir Mat] Univ Sultan Zainal Abidin, Fac Med, Kuala Terengganu, Malaysia.
   [Rupenthal, Ilva D.] Univ Auckland, Dept Ophthalmol, Buchanan Ocular Therapeut Unit, Auckland, New Zealand.
   [Rupenthal, Ilva D.; Green, Colin R.] Univ Auckland, Dept Ophthalmol, Auckland, New Zealand.
C3 University of Auckland; University of Auckland; Universiti Sultan Zainal
   Abidin; University of Auckland; University of Auckland
RP Acosta, ML (通讯作者)，Univ Auckland, Sch Optometry & Vis Sci, Auckland, New Zealand.; Acosta, ML (通讯作者)，Univ Auckland, New Zealand Natl Eye Ctr, Auckland, New Zealand.
EM m.acosta@auckland.ac.nz
RI Acosta, Monica/H-2700-2019; Rupenthal, Ilva D/M-5340-2016; Green, Colin
   R/B-5663-2012
OI Acosta, Monica/0000-0002-5018-339X; Rupenthal, Ilva
   D/0000-0001-5997-5994; Green, Colin R/0000-0003-3459-6298; Mat Nor, Mohd
   Nasir/0000-0001-5654-5593
FU New Zealand Lottery Health Research [3702828]; Auckland UniServices Ltd.
   [5000293]; Maurice and Phyllis Paykel Trust [3708721]; New Zealand
   Optometric Vision Research Foundation [3717092]; Buchanan Charitable
   Foundation; Ministry of Higher Education Malaysia
FX This work was supported in part by New Zealand Lottery Health Research
   (3702828), Auckland UniServices Ltd. (5000293), the Maurice and Phyllis
   Paykel Trust (3708721), and the New Zealand Optometric Vision Research
   Foundation (3717092). C.R.G. acknowledges Professorial support from
   Wendy and Bruce Hadden. I.D.R. Directorship is supported by the Buchanan
   Charitable Foundation. M.N.M.N. held a PhD scholarship from Ministry of
   Higher Education Malaysia.
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NR 56
TC 19
Z9 20
U1 0
U2 6
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 JAN
PY 2020
VL 17
IS 1
SI SI
BP 371
EP 387
DI 10.1007/s13311-019-00786-5
EA OCT 2019
PG 17
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA KI9DV
UT WOS:000491785400001
PM 31637594
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Han, DM
   Wu, XW
   Liu, LB
   Shu, WT
   Huang, ZP
AF Han, Dongmei
   Wu, Xingwei
   Liu, Libin
   Shu, Wanting
   Huang, Zhenping
TI Sodium tanshinone IIA sulfonate protects ARPE-19 cells against oxidative
   stress by inhibiting autophagy and apoptosis
SO SCIENTIFIC REPORTS
LA English
DT Article
ID PHOSPHOINOSITIDE 3-KINASE; TETRAZOLIUM SALT; MITOCHONDRIAL; DEATH;
   PATHWAY; INFLAMMATION; INVOLVEMENT; ACTIVATION; MECHANISMS; CLEARANCE
AB Oxidative stress in retinal pigment epithelium (RPE) is considered to be a major contributor to the development and progression of age-related macular degeneration (AMD). Previous investigations have shown that sodium tanshinone IIA sulfonate (STS) can alleviate oxidative stress in haemorrhagic shock-induced organ damage and cigarette smoke-induced chronic obstructive pulmonary disease in mice. However, whether STS has a protective effect in ARPE-19 cells under oxidative stress and its exact mechanisms have not yet been fully elucidated. In the present study, we utilized H2O2 to establish an oxidative stress environment. Our findings show that STS activated the PI3K/AKT/mTOR pathway to inhibit autophagy and diminished the expression of the autophagic proteins Beclin 1, ATG3, ATG7 and ATG9 in ARPE-19 cells under oxidative stress. Detection of the intrinsic apoptosis-related factors BAX, mitochondrial membrane potential (MMP), caspase-9, caspase-3 and BCL-2, as well as the extrinsic apoptosis-related factors c-FLIP, v-FLIP and caspase-8, confirmed that STS inhibited the intrinsic and extrinsic apoptotic pathways, and attenuated apoptosis in ARPE-19 cells under oxidative stress conditions. These findings shed new light on the protective effects of STS in ARPE-19 cells and its mechanisms under oxidative stress to provide novel and promising therapeutic strategies for AMD.
C1 [Han, Dongmei; Huang, Zhenping] Jinling Hosp, Dept Ophthalmol, Nanjing 210002, Jiangsu, Peoples R China.
   [Wu, Xingwei; Shu, Wanting] Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Ophthalmol, Shanghai 200080, Peoples R China.
   [Liu, Libin] Third Peoples Hosp Jingdezhen, Jingdezhen 333000, Peoples R China.
C3 Shanghai Jiao Tong University
RP Huang, ZP (通讯作者)，Jinling Hosp, Dept Ophthalmol, Nanjing 210002, Jiangsu, Peoples R China.
EM hzp19633@hotmail.com
FU Postdoctoral Foundation in Jiangsu Province [1601120B]; National Natural
   Science Foundation of China [81674027]
FX This work was supported by the Postdoctoral Foundation in Jiangsu
   Province (No. 1601120B) and National Natural Science Foundation of China
   (No. 81674027).
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NR 68
TC 30
Z9 33
U1 8
U2 11
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD OCT 11
PY 2018
VL 8
AR 15137
DI 10.1038/s41598-018-33552-2
PG 15
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA GW6PS
UT WOS:000447083100028
PM 30310136
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Buatois, S
   Ueckert, S
   Frey, N
   Retout, S
   Mentre, F
AF Buatois, Simon
   Ueckert, Sebastian
   Frey, Nicolas
   Retout, Sylvie
   Mentre, France
TI Comparison of Model Averaging and Model Selection in Dose Finding Trials
   Analyzed by Nonlinear Mixed Effect Models
SO AAPS JOURNAL
LA English
DT Article
DE dose-response relationship; model averaging; model selection; nonlinear
   mixed effect models
AB In drug development, pharmacometric approaches consist in identifying via a model selection (MS) process the model structure that best describes the data. However, making predictions using a selected model ignores model structure uncertainty, which could impair predictive performance. To overcome this drawback, model averaging (MA) takes into account the uncertainty across a set of candidate models by weighting them as a function of an information criterion. Our primary objective was to use clinical trial simulations (CTSs) to compare model selection (MS) with model averaging (MA) in dose finding clinical trials, based on the AIC information criterion. A secondary aim of this analysis was to challenge the use of AIC by comparing MA and MS using five different information criteria. CTSs were based on a nonlinear mixed effect model characterizing the time course of visual acuity in wet age-related macular degeneration patients. Predictive performances of the modeling approaches were evaluated using three performance criteria focused on the main objectives of a phase II clinical trial. In this framework, MA adequately described the data and showed better predictive performance than MS, increasing the likelihood of accurately characterizing the dose-response relationship and defining the minimum effective dose. Moreover, regardless of the modeling approach, AIC was associated with the best predictive performances.
C1 [Buatois, Simon; Frey, Nicolas; Retout, Sylvie] F Hoffmann La Rache Ltd, Roche Innovat Ctr Basel, Roche Pharma Res & Early Dev, Pharmaceut Sci, Grenzacherstr 124, CH-4070 Basel, Switzerland.
   [Buatois, Simon; Retout, Sylvie] Inst Roche, 30 Cours Ile Seguin, F-92650 Boulogne, France.
   [Buatois, Simon; Mentre, France] Univ Paris Diderot, Sorbonne Paris Cite, INSERM, UMR 1137,IAME, 16 Rue Henri Huchard, F-75018 Paris, France.
   [Ueckert, Sebastian] Uppsala Univ, Dept Pharmaceut Biosci, Uppsala, Sweden.
C3 Roche Holding; Institut National de la Sante et de la Recherche Medicale
   (Inserm); UDICE-French Research Universities; Universite Paris Cite;
   Uppsala University
RP Buatois, S (通讯作者)，F Hoffmann La Rache Ltd, Roche Innovat Ctr Basel, Roche Pharma Res & Early Dev, Pharmaceut Sci, Grenzacherstr 124, CH-4070 Basel, Switzerland.; Buatois, S (通讯作者)，Inst Roche, 30 Cours Ile Seguin, F-92650 Boulogne, France.; Buatois, S (通讯作者)，Univ Paris Diderot, Sorbonne Paris Cite, INSERM, UMR 1137,IAME, 16 Rue Henri Huchard, F-75018 Paris, France.
EM simon.buatois@inserm.fr
RI Ueckert, Sebastian/AAU-8365-2020; Mentre, France/AFU-8218-2022
OI Ueckert, Sebastian/0000-0002-3712-0255; Mentre,
   France/0000-0002-7045-1275; RETOUT, Sylvie/0000-0003-4867-8438
FU CIFRE agreement (Conventions Industrielles de Formation par la
   Recherche)
FX This work was financed by a CIFRE agreement (Conventions Industrielles
   de Formation par la Recherche) and was conducted under the supervision
   of the ANRT (Association Nationale Recherche Technologie). The CIFRE
   agreement is a partnership between a public laboratory and a company,
   here the UMR 1137 and INSTITUT ROCHE, respectively.
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NR 28
TC 19
Z9 19
U1 0
U2 8
PU SPRINGER
PI NEW YORK
PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
SN 1550-7416
J9 AAPS J
JI AAPS J.
PD MAY
PY 2018
VL 20
IS 3
AR 56
DI 10.1208/s12248-018-0205-x
PG 9
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA GE3TL
UT WOS:000431135700006
PM 29600418
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Ohashi, K
   Kageyama, M
   Shinomiya, K
   Fujita-Koyama, Y
   Hirai, S
   Katsuta, O
   Nakamura, M
AF Ohashi, Koji
   Kageyama, Masaaki
   Shinomiya, Katsuhiko
   Fujita-Koyama, Yukie
   Hirai, Shin-ichiro
   Katsuta, Osamu
   Nakamura, Masatsugu
TI Spermidine Oxidation-Mediated Degeneration of Retinal Pigment Epithelium
   in Rats
SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
LA English
DT Article
ID SODIUM IODATE; CELL-DEATH; B-WAVE; AMINE OXIDASE; MOUSE MODEL;
   APOPTOSIS; STRESS; DAMAGE; ELECTRORETINOGRAM; REGENERATION
AB Retinal pigment epithelium (RPE) degeneration is a crucial event in dry age-related macular degeneration and gyrate atrophy. The polyamine spermidine has been shown to induce RPE cell death in vitro. The present study aimed to establish a novel in vivo model of spermidine-induced RPE degeneration and to determine whether spermidine-induced RPE cell death involves oxidative mechanisms. In this study, spermidine caused ARPE-19 cell death in a concentration-dependentmanner. This effect was prevented by removal of serum from the culture medium or treatment with amine oxidase inhibitors, N-acetylcysteine (NAC), or aldehyde dehydrogenase (ALDH). Intravitreal injection of spermidine into rats significantly increased the permeability of the blood-retinal barrier and decreased the amplitudes of scotopic electroretinogram a-and b-waves. Histological analysis revealed that spermidine induced vacuolation, atrophy, and dropout of RPE cells, leading to the disruption of photoreceptor outer segments. Simultaneous intravitreal administration of NAC and ALDH with spermidine prominently inhibited the functional and morphological changes induced by spermidine. In conclusion, this study demonstrated that the intravitreal administration of spermidine induced RPE cell dysfunction and death followed by photoreceptor degeneration in rats. These effects of spermidine are thought to be mediated by oxidative stress and a toxic aldehyde generated during spermidine oxidation.
C1 [Ohashi, Koji; Kageyama, Masaaki; Shinomiya, Katsuhiko; Fujita-Koyama, Yukie; Hirai, Shin-ichiro; Katsuta, Osamu; Nakamura, Masatsugu] Santen Pharmaceut Co Ltd, Global Res & Dev, Ikoma, Nara, Japan.
C3 Santen Pharmaceutical Co Ltd
RP Ohashi, K (通讯作者)，Santen Pharmaceut Co Ltd, Global Res & Dev, Ikoma, Nara, Japan.
EM koji.ohashi@santen.co.jp
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NR 45
TC 11
Z9 13
U1 1
U2 7
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 1942-0900
EI 1942-0994
J9 OXID MED CELL LONGEV
JI Oxidative Med. Cell. Longev.
PY 2017
VL 2017
AR 4128061
DI 10.1155/2017/4128061
PG 13
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA EQ7BE
UT WOS:000398236700001
PM 28367269
OA gold, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Veritti, D
   Sarao, V
   Parravano, M
   Arias, L
   Varano, M
   Lanzetta, P
AF Veritti, Daniele
   Sarao, Valentina
   Parravano, Mariacristina
   Arias, Luis
   Varano, Monica
   Lanzetta, Paolo
TI One-year results of aflibercept in vascularized pigment epithelium
   detachment due to neovascular AMD: a prospective study
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Aflibercept; Anti-VEGF; Neovascular age-related macular degeneration;
   Pigment epithelium detachment
ID MACULAR DEGENERATION; INTRAVITREAL AFLIBERCEPT; ANATOMICAL OUTCOMES;
   DOSING REGIMEN; RANIBIZUMAB; VEGF; BEVACIZUMAB; THERAPY; EYES; INJECTION
AB Purpose: To evaluate individualized intravitreal aflibercept regimens for treatment of neovascular age-related macular degeneration (nAMD)-related pigment epithelial detachment (PED).
   Methods: This prospective, multicenter, nonrandomized study included 32 eyes with nAMD-related PED, treated with ranibizumab for >= 6 months. All patients received intravitreal aflibercept (2 mg/0.05 mL) at baseline (no loading phase) and subsequently treated pro re nata with monthly follow-up for 12 months. Outcome measures included visual acuity, central retinal thickness (CRT), PED height and area, and neovascular network size.
   Results: At 12 months, aflibercept improved mean best-corrected visual acuity compared with baseline values (p>0.05); 50% of patients displayed complete resolution of intraretinal and/or subretinal fluid. Compared with baseline, significant decreases were observed for mean CRT and PED height (both p<0.01).
   Conclusions: Aflibercept appears to induce anatomical improvement for at least 12 months after conversion from ranibizumab in patients experiencing nAMD-related PED. Significant reductions in both mean PED height and CRT were observed, although these changes were not necessarily related to significantly improved visual acuity scores. However, larger patient cohorts are required to extend and validate our results, and increased study duration would allow exploration of the potential long-term benefits and challenges of prolonged aflibercept use.
C1 [Veritti, Daniele; Sarao, Valentina; Lanzetta, Paolo] Univ Udine, Dept Med & Biol Sci Ophthalmol, Piazzale S Maria della Misericordia, I-33100 Udine, Italy.
   [Veritti, Daniele; Sarao, Valentina; Lanzetta, Paolo] European Inst Ocular Microsurg IEMO, Udine, Italy.
   [Parravano, Mariacristina; Varano, Monica] Fdn GB Bietti, IRCCS, Dept Ophthalmol, Rome, Italy.
   [Arias, Luis] Univ Barcelona, Bellvitge Univ Hosp, Dept Ophthalmol, Barcelona, Spain.
C3 University of Udine; IRCCS - Fondazione "G.B. Bietti" per lo Studio e la
   Ricerca in Oftalmologia; Institut d'Investigacio Biomedica de Bellvitge
   (IDIBELL); Bellvitge University Hospital; University of Barcelona
RP Lanzetta, P (通讯作者)，Univ Udine, Dept Med & Biol Sci Ophthalmol, Piazzale S Maria della Misericordia, I-33100 Udine, Italy.
EM paolo.lanzetta@uniud.it
RI Varano, Monica/K-8573-2016
OI VERITTI, Daniele/0000-0003-0148-5348; Varano, Monica/0000-0002-6530-1563
FU Ministry of Health and Fondazione Roma
FX The research for this paper was partially financially supported by
   Ministry of Health and Fondazione Roma. Medical writing support was
   provided by Samuel Cooper, PhD, of Inspired Science, London, UK.
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NR 38
TC 7
Z9 9
U1 0
U2 6
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1120-6721
EI 1724-6016
J9 EUR J OPHTHALMOL
JI Eur. J. Ophthalmol.
PD JAN-FEB
PY 2017
VL 27
IS 1
BP 74
EP 79
DI 10.5301/ejo.5000880
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA EM1EZ
UT WOS:000395062200019
PM 27791249
DA 2022-11-30
ER

PT J
AU Santovena, A
   Sanchez-Negrin, E
   Gutierrez, F
   Nazco, J
   Farina, JB
AF Santovena, A.
   Sanchez-Negrin, E.
   Gutierrez, F.
   Nazco, J.
   Farina, J. B.
TI Assessment of bevacizumab quality and stability in repackaged syringes
   for clinical use
SO EUROPEAN JOURNAL OF HOSPITAL PHARMACY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; INTRAVITREAL BEVACIZUMAB; MACULAR
   DEGENERATION; EXPERIMENTAL GLAUCOMA; RANIBIZUMAB; INJECTION; AVASTIN;
   AFLIBERCEPT; ENDOPHTHALMITIS; OUTBREAK
AB Objectives Among measures taken to optimise financial resources, the off-label use of bevacizumab (Avastin) in the treatment of age-related macular degeneration (AMD) involves its repackaging from higher volume dosage forms. This use requires studies to analyse the viability of the repackaged preparations to ensure their quality, safety and efficacy. Our aim was to assess the structural stability and particle size of bevacizumab after it was repackaged from the original glass vials and stored in plastic syringes.
   Methods High performance liquid chromatography by size exclusion (HPLC-SE) was used to quantify the bevacizumab and determine its degradation products after stress stability testing, with a particle size counter employed after repackaging and subsequent storage.
   Results The syringes stored for 3 days at 4 degrees C maintained the area of the main chromatographic peak above 100+/-10% of its initial value, and the observed particle size is the same as at baseline (20 nm) but with a double distribution towards larger sizes.
   Conclusions This study shows how the repackaging of Avastin in plastic syringes permits their use for 3 days if stored under normal refrigeration. In this way, hospital pharmacy services can help optimise health resources without compromising the pharmaceutical standards of the drug.
C1 [Santovena, A.; Sanchez-Negrin, E.; Farina, J. B.] Univ La Laguna, Inst Enfermedades Trop & Salud Publ Canarias, Tenerife, Spain.
   [Gutierrez, F.; Nazco, J.] Hosp Univ Canarias, Serv Farm Hosp, Tenerife, Spain.
C3 Universidad de la Laguna; Universidad de la Laguna
RP Santovena, A (通讯作者)，Univ La Laguna, Fac Farm, Dept Ingn Quim & Tecnol Farmaceut, Tenerife 38200, Spain.
EM ansanto@ull.es
RI Santoveña, Ana/ABE-5830-2020; /A-5798-2008
OI Farina, Jose/0000-0001-8320-3978; Santovena, Ana/0000-0002-3424-7824
FU Ministerio de Ciencia e Innovacion [SAF2010-17083]
FX The Ministerio de Ciencia e Innovacion funded this study
   (SAF2010-17083).
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NR 36
TC 1
Z9 1
U1 0
U2 10
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 2047-9956
EI 2047-9964
J9 EUR J HOSP PHARM
JI Eur. J. Hosp. Pharm.
PD NOV
PY 2016
VL 23
IS 6
BP 343
EP 347
DI 10.1136/ejhpharm-2015-000853
PG 5
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA EE1JI
UT WOS:000389337000009
PM 31156880
OA Green Published
DA 2022-11-30
ER

PT J
AU Sulaiman, RS
   Merrigan, S
   Quigley, J
   Qi, XP
   Lee, B
   Boulton, ME
   Kennedy, B
   Seo, SY
   Corson, TW
AF Sulaiman, Rania S.
   Merrigan, Stephanie
   Quigley, Judith
   Qi, Xiaoping
   Lee, Bit
   Boulton, Michael E.
   Kennedy, Breandan
   Seo, Seung-Yong
   Corson, Timothy W.
TI A novel small molecule ameliorates ocular neovascularisation and
   synergises with anti-VEGF therapy
SO SCIENTIFIC REPORTS
LA English
DT Article
ID CHOROIDAL NEOVASCULARIZATION; RETINAL NEOVASCULARIZATION; INTRAVITREAL
   INJECTION; MACULAR DEGENERATION; HOMOISOFLAVANONE; ANGIOGENESIS;
   RETINOPATHY; INHIBITION; MECHANISMS; MODEL
AB Ocular neovascularisation underlies blinding eye diseases such as retinopathy of prematurity, proliferative diabetic retinopathy, and wet age-related macular degeneration. These diseases cause irreversible vision loss, and provide a significant health and economic burden. Biologics targeting vascular endothelial growth factor (VEGF) are the major approach for treatment. However, up to 30% of patients are non-responsive to these drugs and they are associated with ocular and systemic side effects. Therefore, there is a need for small molecule ocular angiogenesis inhibitors to complement existing therapies. We examined the safety and therapeutic potential of SH-11037, a synthetic derivative of the antiangiogenic homoisoflavonoid cremastranone, in models of ocular neovascularisation. SH-11037 dose-dependently suppressed angiogenesis in the choroidal sprouting assay ex vivo and inhibited ocular developmental angiogenesis in zebrafish larvae. Additionally, intravitreal SH-11037 (1 mu M) significantly reduced choroidal neovascularisation (CNV) lesion volume in the laser-induced CNV mouse model, comparable to an anti-VEGF antibody. Moreover, SH11037 synergised with anti-VEGF treatments in vitro and in vivo. Up to 100 mu M SH-11037 was not associated with signs of ocular toxicity and did not interfere with retinal function or pre-existing retinal vasculature. SH-11037 is thus a safe and effective treatment for murine ocular neovascularisation, worthy of further mechanistic and pharmacokinetic evaluation.
C1 [Sulaiman, Rania S.; Quigley, Judith; Qi, Xiaoping; Boulton, Michael E.; Corson, Timothy W.] Indiana Univ Sch Med, Dept Ophthalmol, Eugene & Marilyn Glick Eye Inst, Indianapolis, IN 46202 USA.
   [Sulaiman, Rania S.; Corson, Timothy W.] Indiana Univ Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA.
   [Sulaiman, Rania S.] Cairo Univ, Fac Pharm, Dept Biochem, Cairo, Egypt.
   [Merrigan, Stephanie] Univ Coll Dublin, Conway Inst, Sch Biomol & Biomed Sci, Dublin 4, Ireland.
   [Lee, Bit; Seo, Seung-Yong] Gachon Univ, Coll Pharm, Inchon 406840, South Korea.
   [Boulton, Michael E.; Corson, Timothy W.] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA.
C3 Indiana University System; Indiana University Bloomington; Indiana
   University System; Indiana University Bloomington; Egyptian Knowledge
   Bank (EKB); Cairo University; University College Dublin; Gachon
   University; Indiana University System; Indiana University Bloomington
RP Corson, TW (通讯作者)，Indiana Univ Sch Med, Dept Ophthalmol, Eugene & Marilyn Glick Eye Inst, Indianapolis, IN 46202 USA.; Corson, TW (通讯作者)，Indiana Univ Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA.; Corson, TW (通讯作者)，Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA.
EM tcorson@iupui.edu
RI Corson, Timothy W./B-6851-2009; kennedy, Breandan/H-5643-2019
OI Corson, Timothy W./0000-0002-1402-7875; kennedy,
   Breandan/0000-0001-7991-4689
FU International Retinal Research Foundation; Retina Research Foundation;
   Bright Focus Foundation; NIH/NEI [R01EY025641, R01EY018358]; Basic
   Science Research Program through the National Research Foundation of
   Korea (NRF) - Ministry of Education [NRF-2013R1A1A2007151]; NIH/NCATS
   [KL2TR001106]; Research to Prevent Blindness, Inc.; NATIONAL CENTER FOR
   ADVANCING TRANSLATIONAL SCIENCES [UL1TR001108, KL2TR001106] Funding
   Source: NIH RePORTER; NATIONAL EYE INSTITUTE [R01EY018358, R01EY025641]
   Funding Source: NIH RePORTER
FX We thank Keith Condon, Indiana University School of Medicine Histology
   Core for his help sectioning the eye samples and carrying out H&E
   staining. This work was supported by grants from the International
   Retinal Research Foundation, the Retina Research Foundation, the Bright
   Focus Foundation, and NIH/NEI R01EY025641 to T.W.C., NIH/NEI R01EY018358
   to M.E.B., and support from the Basic Science Research Program through
   the National Research Foundation of Korea (NRF) funded by the Ministry
   of Education (NRF-2013R1A1A2007151) to S.-Y.S. This publication was also
   made possible in part by NIH/NCATS KL2TR001106, and by an unrestricted
   grant from Research to Prevent Blindness, Inc.
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NR 45
TC 45
Z9 46
U1 2
U2 21
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD MAY 5
PY 2016
VL 6
AR 25509
DI 10.1038/srep25509
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA DL3PS
UT WOS:000375546300001
PM 27148944
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Liyanage, SE
   Fantin, A
   Villacampa, P
   Lange, CA
   Denti, L
   Cristante, E
   Smith, AJ
   Ali, RR
   Luhmann, UF
   Bainbridge, JW
   Ruhrberg, C
AF Liyanage, Sidath E.
   Fantin, Alessandro
   Villacampa, Pilar
   Lange, Clemens A.
   Denti, Laura
   Cristante, Enrico
   Smith, Alexander J.
   Ali, Robin R.
   Luhmann, Ulrich F.
   Bainbridge, James W.
   Ruhrberg, Christiana
TI Myeloid-Derived Vascular Endothelial Growth Factor and Hypoxia-Inducible
   Factor Are Dispensable for Ocular Neovascularization-Brief Report
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE choroidal neovascularization; diabetic retinopathy; macular
   degeneration; myeloid cells; vascular endothelial growth factor A
ID EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; RETINAL-PIGMENT EPITHELIUM;
   OXYGEN-INDUCED RETINOPATHY; VITREAL MACROPHAGES; VEGF; ANGIOGENESIS;
   CELLS; EXPRESSION; ROLES; MOUSE
AB Objective Ocular neovascularization (ONV) is a pathological feature of sight-threatening human diseases, such as diabetic retinopathy and age-related macular degeneration. Macrophage depletion in mouse models of ONV reduces the formation of pathological blood vessels, and myeloid cells are widely considered an important source of the vascular endothelial growth factor A (VEGF). However, the importance of VEGF or its upstream regulators hypoxia-inducible factor-1 (HIF1) and hypoxia-inducible factor-2 (HIF2) as myeloid-derived regulators of ONV remains to be determined.
   Approach and Results We used 2 mouse models of ONV, choroidal neovascularization and oxygen-induced retinopathy, to show that Vegfa is highly expressed by several cell types, but not myeloid cells during ONV. Moreover, myeloid-specific VEGF ablation did not reduce total ocular VEGF during choroidal neovascularization or oxygen-induced retinopathy. In agreement, the conditional inactivation of Vegfa, Hif1a, or Epas1 in recruited and resident myeloid cells that accumulated at sites of neovascularization did not significantly reduce choroidal neovascularization or oxygen-induced retinopathy.
   Conclusions The finding that myeloid cells are not a significant local source of VEGF in these rodent models of ONV suggests that myeloid function in neovascular eye disease differs from skin wound healing and other neovascular pathologies.
C1 [Liyanage, Sidath E.; Villacampa, Pilar; Lange, Clemens A.; Cristante, Enrico; Smith, Alexander J.; Ali, Robin R.; Luhmann, Ulrich F.; Bainbridge, James W.] UCL, UCL Inst Ophthalmol, Div Genet, London EC1V 9EL, England.
   [Fantin, Alessandro; Denti, Laura; Ruhrberg, Christiana] UCL, UCL Inst Ophthalmol, Div Cell Biol, London EC1V 9EL, England.
C3 University of London; University College London; University of London;
   University College London
RP Ruhrberg, C (通讯作者)，UCL, UCL Inst Ophthalmol, Div Cell Biol, 11-43 Bath St, London EC1V 9EL, England.
EM j.bainbridge@ucl.ac.uk; c.ruhrberg@ucl.ac.uk
RI Ruhrberg, Christiana/C-6404-2009; Fantin, Alessandro/R-4601-2017;
   Villacampa, Pilar/B-1801-2019
OI Ruhrberg, Christiana/0000-0002-3212-9381; Fantin,
   Alessandro/0000-0002-5517-6068; Villacampa, Pilar/0000-0002-2860-7475;
   Luhmann, Ulrich F.O./0000-0002-1993-1951; Ali,
   Robin/0000-0003-3126-6517; Bainbridge, James/0000-0003-1318-8201
FU joint Medical Research Council; Fight for Sight grant [MR/K003003/1];
   People Programme (Marie Curie Actions); European Union's Seventh
   Framework Programme (FP7) under Research Executive Agency [629556];
   Special Trustees of Moorfields Eye Hospital [ST 1503B]; Wellcome Trust
   [095623/Z/11/Z]; Medical Research Council [MR/L022699/1, MR/K003003/1]
   Funding Source: researchfish; National Institute for Health Research
   [NIHR-RP-011-003, NF-SI-0513-10074] Funding Source: researchfish; Fight
   for Sight [1333/34] Funding Source: researchfish; MRC [MR/K003003/1,
   MR/L022699/1] Funding Source: UKRI
FX This study was supported by a joint Medical Research Council and Fight
   for Sight grant (MR/K003003/1) to S.E. Liyanage, the People Programme
   (Marie Curie Actions) and the European Union's Seventh Framework
   Programme (FP7/2007-2013) under Research Executive Agency grant
   agreement 629556 to P. Villacampa, the Special Trustees of Moorfields
   Eye Hospital (Grant ST 1503B) to J.W. Bainbridge and funding from the
   Wellcome Trust (095623/Z/11/Z) to C. Ruhrberg; J.W. Bainbridge is a
   Research Professor of the National Institute of Health Research.
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NR 38
TC 28
Z9 29
U1 0
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1079-5642
EI 1524-4636
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD JAN
PY 2016
VL 36
IS 1
BP 19
EP 24
DI 10.1161/ATVBAHA.115.306681
PG 6
WC Hematology; Peripheral Vascular Disease
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Hematology; Cardiovascular System & Cardiology
GA CZ3JI
UT WOS:000367000000006
PM 26603154
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Tsai, YC
   Lu, B
   Bakondi, B
   Girman, S
   Sahabian, A
   Sareen, D
   Svendsen, CN
   Wang, SM
AF Tsai, Yuchun
   Lu, Bin
   Bakondi, Benjamin
   Girman, Sergey
   Sahabian, Anais
   Sareen, Dhruv
   Svendsen, Clive N.
   Wang, Shaomei
TI Human iPSC-Derived Neural Progenitors Preserve Vision in an AMD-Like
   Model
SO STEM CELLS
LA English
DT Article
DE Induced pluripotent stem cells; Retinal degeneration; Clinical
   translation; Progenitor cells; Stem cell transplantation
ID AMYOTROPHIC-LATERAL-SCLEROSIS; PLURIPOTENT STEM-CELLS; MACULAR
   DEGENERATION; RETINAL DEGENERATION; RAT MODEL; PHOTORECEPTOR
   DEGENERATION; SUBRETINAL SPACE; RCS RATS; TRANSPLANTATION; INTEGRATE
AB Pluripotent stem cell-derived retinal pigment epithelial (RPE) cells are currently being tested for cell replacement in late-stage age-related macular degeneration (AMD). However, preserving vision at early-stages may also be possible. Here, we demonstrate that transplantation of neural progenitor cells (NPCs) derived from induced pluripotent stem cells (iNPCs) limits disease progression in the Royal College of Surgeons rat, a preclinical model of AMD. Grafted-iNPCs survived, remained undifferentiated, and distributed extensively in a laminar fashion in the subretinal space. Retinal pathology resulting from the accumulation of undigested photoreceptor outer segments (POS) was significantly reduced in iNPC-injected rats compared with controls. Phagosomes within grafted-iNPCs contained POS, suggesting that iNPCs had compensated for defective POS phagocytosis by host-RPE. The iNPC-treated eyes contained six to eight rows of photoreceptor nuclei that spanned up to 5mm in length in transverse retinal sections, compared with only one row of photoreceptors in controls. iNPC treatment fully preserved visual acuity measured by optokinetic response. Electrophysiological recordings revealed that retina with the best iNPC-protected areas were 140-fold more sensitive to light stimulation than equivalent areas of contralateral eyes. The results described here support the therapeutic utility of iNPCs as autologous grafts for early-stage of AMD.
C1 [Tsai, Yuchun; Lu, Bin; Bakondi, Benjamin; Girman, Sergey; Sahabian, Anais; Sareen, Dhruv; Svendsen, Clive N.; Wang, Shaomei] Cedars Sinai Med Ctr, Board Governors Regenerat Med Inst, Dept Biomed Sci, Los Angeles, CA 90048 USA.
C3 Cedars Sinai Medical Center
RP Wang, SM (通讯作者)，Cedars Sinai Med Ctr, 8700 Beverly Blvd, Los Angeles, CA 90048 USA.
EM shaomei.wang@cshs.org
OI Bakondi, Benjamin/0000-0003-3319-9784
FU Simon and Beatrice Apple Stem Cell Fund for Eye Research; David and
   Janet Polak Foundation Stem Cell Core Laboratory; NIH [R01 EY020488];
   Department of Defense [W81XWH-12-1-0617]; Foundation Fighting Blindness,
   Board of Governors Regenerative Medicine Institute at Cedars-Sinai
   Medical Center; Knights Templar Eye Foundation, Inc.; NATIONAL EYE
   INSTITUTE [R01EY020488] Funding Source: NIH RePORTER
FX This work was supported by The Simon and Beatrice Apple Stem Cell Fund
   for Eye Research, David and Janet Polak Foundation Stem Cell Core
   Laboratory; NIH (R01 EY020488), Department of Defense
   (W81XWH-12-1-0617), Foundation Fighting Blindness, Board of Governors
   Regenerative Medicine Institute at Cedars-Sinai Medical Center, Knights
   Templar Eye Foundation, Inc. (Y.T.). We thank Dr. Soshana Svendsen and
   Melissa K. Jones for review and editing, Dr. Gouping Fan for providing
   human fetal RPE cells, Dr. Alberto Yanez for assistance with flow
   cytometry, and the Cedars-Sinai Medical Center Microscopy Core for
   assistance with electron microscopy.
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NR 35
TC 34
Z9 35
U1 1
U2 10
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1066-5099
EI 1549-4918
J9 STEM CELLS
JI Stem Cells
PD AUG
PY 2015
VL 33
IS 8
BP 2537
EP 2549
DI 10.1002/stem.2032
PG 13
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
   Oncology; Cell Biology; Hematology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA CN1UP
UT WOS:000358206000015
PM 25869002
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU Shen, JK
   Choy, DF
   Yoshida, T
   Iwase, T
   Hafiz, G
   Xie, B
   Hackett, SF
   Arron, JR
   Campochiaro, PA
AF Shen, Jikui
   Choy, David F.
   Yoshida, Tsunehiko
   Iwase, Takeshi
   Hafiz, Gulnar
   Xie, Bing
   Hackett, Sean F.
   Arron, Joseph R.
   Campochiaro, Peter A.
TI Interleukin-18 Has Antipermeablity and Antiangiogenic Activities in the
   Eye: Reciprocal Suppression With VEGF
SO JOURNAL OF CELLULAR PHYSIOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL VEIN OCCLUSION; CHOROIDAL
   NEOVASCULARIZATION; MACULAR EDEMA; SUSTAINED BENEFITS; 12-MONTH
   OUTCOMES; INDUCED BREAKDOWN; RANIBIZUMAB; IL-18; INHIBITION
AB Interleukin-18 (IL-18) is increased along with IL-1 by activation of the inflammasome and has been implicated in inflammatory and autoimmune diseases, but its role in the eye is uncertain. In patients with macular edema due to retinal vein occlusion, intraocular IL-18 levels increased significantly (P<0.001) after treatment with ranibizumab particularly in patients with high baseline IL-18 which correlated with good visual outcome (P<0.05). In mice with ischemic retinopathy, suppression of VEGF caused an increase in IL18 mRNA due to an increase in IL-18-positive myeloid cells. VEGF significantly and specifically inhibited IL-18 production by myeloid cells stimulated with lipopolysaccharide (P<0.001). Intraocular injection of IL-18 reduced VEGF-induced leakage and neovascularization, and reversed VEGF-induced suppression of Claudin5 expression and Claudin 5 labeling of vascular tight junctions. Injection of IL-18 also increased expression of Thrombospondin 1 and reduced ischemia-induced retinal neovascularization relevant to diabetic retinopathy and subretinal neovascularization relevant to neovascular age-related macular degeneration. Thus, VEGF and IL-18 suppress each other's production and effects on the vasculature suggesting that IL-18 may provide benefit in multiple retinal/choroidal vascular diseases. J. Cell. Physiol. 229: 974-983, 2014. (c) 2013 Wiley Periodicals, Inc.
C1 [Shen, Jikui; Yoshida, Tsunehiko; Iwase, Takeshi; Xie, Bing; Hackett, Sean F.; Campochiaro, Peter A.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA.
   [Shen, Jikui; Yoshida, Tsunehiko; Iwase, Takeshi; Xie, Bing; Hackett, Sean F.; Campochiaro, Peter A.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA.
   [Choy, David F.; Arron, Joseph R.] Genentech Inc, Immunol Tissue Growth & Repair Diagnost Discovery, San Francisco, CA 94080 USA.
C3 Johns Hopkins University; Johns Hopkins University; Roche Holding;
   Genentech
RP Campochiaro, PA (通讯作者)，Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Maumenee 719,600 North Wolfe St, Baltimore, MD 21287 USA.
EM pcampo@jhmi.edu
RI Iwase, Takeshi/H-8110-2015
OI Xie, Bing/0000-0003-2335-5966; Choy, David/0000-0003-1351-6113; Arron,
   Joseph/0000-0001-7677-9979
FU National Eye Institute [EY012609]; Genentech; NATIONAL EYE INSTITUTE
   [R01EY005951, R01EY012609] Funding Source: NIH RePORTER
FX Contract grant sponsor: National Eye Institute;; Contract grant number:
   EY012609.; Contract grant sponsor: Genentech (Investigator Initiated
   Study grant).
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NR 47
TC 35
Z9 36
U1 0
U2 6
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9541
EI 1097-4652
J9 J CELL PHYSIOL
JI J. Cell. Physiol.
PD AUG
PY 2014
VL 229
IS 8
BP 974
EP 983
DI 10.1002/jcp.24575
PG 10
WC Cell Biology; Physiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Physiology
GA AF7SV
UT WOS:000334915900002
PM 24515951
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Mendis, R
   Lois, N
AF Mendis, Randev
   Lois, Noemi
TI Fundus autofluorescence in patients with retinal pigment epithelial
   (RPE) tears: an in-vivo evaluation of RPE resurfacing
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Retinal pigment epithelium; Retinal pigment epithelial tears;
   Autofluorescence; Age-related macular degeneration
ID CHOROIDAL NEOVASCULARIZATION SECONDARY; MACULAR DEGENERATION;
   INTRAVITREAL RANIBIZUMAB; INJECTION
AB Investigate RPE resurfacing by changes in fundus autofluorescence (AF) in patients with retinal pigment epithelial (RPE) tears secondary to age-related macular degeneration (AMD).
   A retrospective case series of patients presenting with RPE tears from 1 March 2008 to 1 April 2011. The pattern and area of AF signal distribution in RPE tears were evaluated. The change in the size of the area of debrided RPE over the follow-up period was used as the main outcome measure. A reduction in this area was termed "RPE resurfacing", and an enlargement termed "progression of RPE cell loss".
   Thirteen patients (14 eyes) with RPE tears (mean age 82 years) were included in this study. The mean baseline area of reduced AF signal was 4.1 mm(2) (range 0.33-14.9, median 0.29). "Resurfacing" of the RPE occurred in ten eyes and "progression of RPE cell loss" in four eyes after a median follow-up of 11.5 months (range, 1-39). The mean area of healing was 2.0 mm(2), and progression was 1.78 mm(2).
   A consistent AF pattern was observed in patients with RPE tears. RPE resurfacing over the area of the RPE tear occurred, to a varying degree, in the majority of the cases.
C1 [Mendis, Randev] Grampian Univ Hosp NHS Trust, Dept Ophthalmol, Aberdeen AB25 2ZN, Scotland.
   [Lois, Noemi] Queens Univ Belfast, Ctr Vasc & Visual Sci, Belfast, Antrim, North Ireland.
   [Mendis, Randev] Canberra Hosp, Dept Ophthalmol, ACT Govt Hlth, Canberra, ACT 2605, Australia.
C3 University of Aberdeen; Queens University Belfast; Australian National
   University; Canberra Hospital
RP Lois, N (通讯作者)，Queens Univ Belfast, Ctr Vasc & Visual Sci, Belfast, Antrim, North Ireland.
EM n.lois@qub.ac.uk
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NR 22
TC 14
Z9 16
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 JUL
PY 2014
VL 252
IS 7
BP 1059
EP 1063
DI 10.1007/s00417-013-2549-3
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AK5US
UT WOS:000338492500005
PM 24407824
DA 2022-11-30
ER

PT J
AU Ablonczy, Z
   Higbee, D
   Grey, AC
   Koutalos, Y
   Schey, KL
   Crouch, RK
AF Ablonczy, Zsolt
   Higbee, Daniel
   Grey, Angus C.
   Koutalos, Yiannis
   Schey, Kevin L.
   Crouch, Rosalie K.
TI Similar molecules spatially correlate with lipofuscin and
   N-retinylidene-N-retinylethanolamine in the mouse but not in the human
   retinal pigment epithelium
SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
LA English
DT Article
DE Lipofuscin; A2E; Retinoids; Mass spectrometry; Imaging; Human; Mouse;
   MALDI; Profiling; RPE
ID A2E; FLUORESCENCE; BIOSYNTHESIS; FLUOROPHORES; ACCUMULATION; PRECURSOR;
   NEURONS; BRAIN; ROD
AB The accumulation of lipofuscin in the retinal pigment epithelium (RPE) has been implicated in the development of age-related macular degeneration (AMD) in humans. The exact composition of lipofuscin is not known but its best characterized component is N-retinylidene-N-retinylethanolamine (A2E), a byproduct of the retinoid visual cycle. Utilizing our recently developed matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS)-based technique to determine the spatial distribution of A2E, this study compares the relationships of lipofuscin fluorescence and A2E in the murine and human RPE on representative normal tissue. To identify molecules with similar spatial patterns, the images of A2E and lipofuscin were correlated with all the individual images in the MALDI-IMS dataset In the murine RPE, there was a remarkable correlation between A2E and lipofuscin. In the human RPE, however, minimal correlation was detected. These results were reflected in the marked distinctions between the molecules that spatially correlated with the images of lipofuscin and A2E in the human RPE. While the distribution of murine lipofuscin showed highest similarities with some of the known A2E-adducts, the composition of human lipofuscin was significantly different. These results indicate that A2E metabolism may be altered in the human compared to the murine RPE. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Ablonczy, Zsolt; Koutalos, Yiannis; Crouch, Rosalie K.] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.
   [Higbee, Daniel] New York Drug Testing & Res Program, Ithaca, NY 14850 USA.
   [Grey, Angus C.] Univ Auckland, Dept Physiol, Auckland 1023, New Zealand.
   [Schey, Kevin L.] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37240 USA.
C3 Medical University of South Carolina; University of Auckland; Vanderbilt
   University
RP Ablonczy, Z (通讯作者)，Med Univ S Carolina, Storm Eye Inst, Rm 518E,167 Ashley Ave, Charleston, SC 29425 USA.
EM ablonczy@musc.edu
RI Grey, Angus/O-3473-2019; Grey, Gus/J-7024-2015
OI Grey, Angus/0000-0002-1540-1080; Grey, Gus/0000-0002-1540-1080
FU NIH [R21 EY020661, R01 EY004939, R01 EY014850, R01 EY019728, R01
   EY19065]; Research to Prevent Blindness (RPB; New York); Cancer Center
   Support Grant [P30 CA138313]; Hollings Cancer Center, MUSC; NATIONAL
   CANCER INSTITUTE [P30CA138313] Funding Source: NIH RePORTER; NATIONAL
   EYE INSTITUTE [R01EY004939, R01EY014850, R01EY019065, R21EY020661,
   R21EY019728] Funding Source: NIH RePORTER
FX This study was supported in part by NIH grants R21 EY020661 (ZA/RKC),
   R01 EY004939 (RKC), R01 EY014850 (YK), R01 EY019728 (KS) and R01 EY19065
   (ZA); and an unrestricted grant to the Department of Ophthalmology at
   MUSC from Research to Prevent Blindness (RPB; New York); RKC is an RPB
   Senior Scientific Investigator. The work has in part been conducted in
   the MUSC Mass Spectrometry Institutional Research Resource Facility and
   in the Cell 82 Molecular Imaging Shared Resource of the Hollings Cancer
   Center which was supported by Cancer Center Support Grant P30 CA138313
   to the Hollings Cancer Center, MUSC.
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NR 36
TC 27
Z9 27
U1 0
U2 8
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 NOV 15
PY 2013
VL 539
IS 2
BP 196
EP 202
DI 10.1016/j.abb.2013.08.005
PG 7
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 250ND
UT WOS:000326858600013
PM 23969078
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Tosini, G
   Baba, K
   Hwang, CK
   Iuvone, PM
AF Tosini, Gianluca
   Baba, Kenkichi
   Hwang, Christopher K.
   Iuvone, P. Michael
TI Melatonin: An underappreciated player in retinal physiology and
   pathophysiology
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Review
DE melatonin; circadian rhythms; dopamine; glaucoma; photoreceptor
   degeneration; retina
ID ARYLALKYLAMINE N-ACETYLTRANSFERASE; TRYPTOPHAN-HYDROXYLASE ACTIVITY;
   XENOPUS-LAEVIS RETINA; BRAIN ARYL ACYLAMIDASE; GUINEA-PIG RETINA;
   CIRCADIAN CLOCK; MESSENGER-RNA; RAT RETINA; INTRAOCULAR-PRESSURE;
   PHOTORECEPTOR CELLS
AB In the vertebrate retina, melatonin is synthesized by the photoreceptors with high levels of melatonin at night and lower levels during the day. Melatonin exerts its influence by interacting with a family of G-protein-coupled receptors that are negatively coupled with adenylyl cyclase. Melatonin receptors belonging to the subtypes MT1 and MT2 have been identified in the mammalian retina. MT1 and MT2 receptors are found in all layers of the neural retina and in the retinal pigmented epithelium. Melatonin in the eye is believed to be involved in the modulation of many important retinal functions; it can modulate the electroretinogram (ERG), and administration of exogenous melatonin increases light-induced photoreceptor degeneration. Melatonin may also have protective effects on retinal pigment epithelial cells, photoreceptors and ganglion cells. A series of studies have implicated melatonin in the pathogenesis of age-related macular degeneration, and melatonin administration may represent a useful approach to prevent and treat glaucoma. Melatonin is used by millions of people around the world to retard aging, improve sleep performance, mitigate jet lag symptoms, and treat depression. Administration of exogenous melatonin at night may also be beneficial for ocular health, but additional investigation is needed to establish its potential. (c) 2012 Elsevier Ltd. All rights reserved.
C1 [Tosini, Gianluca; Baba, Kenkichi] Morehouse Sch Med, Circadian Rhythms & Sleep Disorders Program, Inst Neurosci, Atlanta, GA 30310 USA.
   [Tosini, Gianluca; Baba, Kenkichi] Morehouse Sch Med, Dept Pharmacol & Toxicol, Atlanta, GA 30310 USA.
   [Hwang, Christopher K.; Iuvone, P. Michael] Emory Univ, Dept Ophthalmol, Sch Med, Atlanta, GA 30322 USA.
   [Hwang, Christopher K.; Iuvone, P. Michael] Emory Univ, Dept Pharmacol, Sch Med, Atlanta, GA 30322 USA.
C3 Morehouse School of Medicine; Morehouse School of Medicine; Emory
   University; Emory University
RP Tosini, G (通讯作者)，Morehouse Sch Med, Circadian Rhythms & Sleep Disorders Program, Inst Neurosci, Atlanta, GA 30310 USA.
EM gtosini@msm.edu
OI tosini, gianluca/0000-0003-3645-4533
FU National Institutes of Health [R01 NS43459, R21 EY028821, R01 EY022216,
   R01 EY004864, P30 EY006360]; Research to Prevent Blindness, Inc. (RPB);
   RPB; NATIONAL EYE INSTITUTE [R01EY004864, P30EY006360, R21EY020821,
   R01EY022216] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF
   NEUROLOGICAL DISORDERS AND STROKE [R56NS043459, R01NS043459] Funding
   Source: NIH RePORTER
FX Research in the authors' laboratories is supported by grants from the
   National Institutes of Health [R01 NS43459, R21 EY028821, R01 EY022216
   (GT); R01 EY004864 (PMI), P30 EY006360 (PMI)], and Research to Prevent
   Blindness, Inc. (RPB) (PMI). PMI is a recipient of Senior Scientific
   Investigator Award from RPB.
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NR 145
TC 95
Z9 105
U1 3
U2 44
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 2012
VL 103
BP 82
EP 89
DI 10.1016/j.exer.2012.08.009
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 018FX
UT WOS:000309646700012
PM 22960156
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Lee, MY
   Yoon, J
   Ham, DI
AF Lee, Mee Yon
   Yoon, Jaemoon
   Ham, Don-Il
TI Clinical features of reticular pseudodrusen according to the fundus
   distribution
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; AGE-RELATED MACULOPATHY; MACULAR
   DEGENERATION; PREVALENCE; DRUSEN
AB Background To evaluate the morphological features and prevalence of accompanying late age-related macular degeneration (AMD) according to the fundus distribution of reticular pseudodrusen (RPD).
   Methods According to the involved area in the fundus, the distribution of RPD was classified as localised, intermediate, or diffuse type. Morphology of RPD was classified as discrete, branching, or confluent pattern. The presence of late AMD was evaluated.
   Results 233 eyes of 121 patients with RPD were included. The distribution of RPD was localised, intermediate and diffuse type in 30.9%, 40.3% and 28.8% of eyes, respectively. The discrete, branching and confluent morphological patterns were found in 45.8%, 44.8% and 9.7% of the localised type, and in 0%, 13.8% and 86.2% of the intermediate type, respectively. In contrast, the diffuse type showed only the confluent morphological pattern. The prevalence of accompanying late AMD was 13.9%, 13.8% and 56.7% in the localised, intermediate and diffuse type, respectively, and it was significantly higher in the diffuse type (p<0.05).
   Conclusion RPD with diffuse distribution showed a confluent morphological pattern and a high prevalence of late AMD. RPD can be classified by the fundus distribution for the assessment of visual prognosis.
C1 [Yoon, Jaemoon; Ham, Don-Il] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Ophthalmol, Seoul 135710, South Korea.
   [Lee, Mee Yon] Chung Ang Univ, Coll Med, Dept Ophthalmol, Seoul 156756, South Korea.
C3 Sungkyunkwan University (SKKU); Samsung Medical Center; Chung Ang
   University; Chung Ang University Hospital
RP Ham, DI (通讯作者)，Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Ophthalmol, 50 Irwon Dong, Seoul 135710, South Korea.
EM oculus@naver.com
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NR 26
TC 36
Z9 39
U1 0
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD SEP
PY 2012
VL 96
IS 9
BP 1222
EP 1226
DI 10.1136/bjophthalmol-2011-301207
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 004IH
UT WOS:000308674500014
PM 22773089
DA 2022-11-30
ER

PT J
AU Lin, WY
   Lee, WC
AF Lin, Wan-Yu
   Lee, Wen-Chung
TI Presenting the Uncertainties of Odds Ratios Using Empirical-Bayes
   Prediction Intervals
SO PLOS ONE
LA English
DT Article
ID FALSE DISCOVERY RATE; CONFIDENCE-INTERVALS; MAXIMUM-LIKELIHOOD;
   ASSOCIATION; SERIES
AB Quantifying exposure-disease associations is a central issue in epidemiology. Researchers of a study often present an odds ratio (or a logarithm of odds ratio, logOR) estimate together with its confidence interval (CI), for each exposure they examined. Here the authors advocate using the empirical-Bayes-based 'prediction intervals' (PIs) to bound the uncertainty of logORs. The PI approach is applicable to a panel of factors believed to be exchangeable (no extra information, other than the data itself, is available to distinguish some logORs from the others). The authors demonstrate its use in a genetic epidemiological study on age-related macular degeneration (AMD). The proposed PIs can enjoy straightforward probabilistic interpretations-a 95% PI has a probability of 0.95 to encompass the true value, and the expected number of true values that are being encompassed is 0.95m for a total of m 95% PIs. The PI approach is theoretically more efficient (producing shorter intervals) than the traditional CI approach. In the AMD data, the average efficiency gain is 51.2%. The PI approach is advocated to present the uncertainties of many logORs in a study, for its straightforward probabilistic interpretations and higher efficiency while maintaining the nominal coverage probability.
C1 [Lin, Wan-Yu; Lee, Wen-Chung] Natl Taiwan Univ, Coll Publ Hlth, Inst Epidemiol & Prevent Med, Taipei 10764, Taiwan.
   [Lin, Wan-Yu] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA.
   [Lee, Wen-Chung] Natl Taiwan Univ, Res Ctr Genes Environm & Human Hlth, Taipei 10764, Taiwan.
C3 National Taiwan University; University of Alabama System; University of
   Alabama Birmingham; National Taiwan University
RP Lin, WY (通讯作者)，Natl Taiwan Univ, Coll Publ Hlth, Inst Epidemiol & Prevent Med, Taipei 10764, Taiwan.
EM wenchung@ntu.edu.tw
RI Huang, HsiaoYuan/F-5985-2012
OI Lee, Wen-Chung/0000-0003-3171-7672; LIN, WAN-YU/0000-0002-3385-4702
FU National Science Councils, Taiwan
FX This study was supported by National Science Councils, Taiwan. The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
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NR 38
TC 0
Z9 0
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 21
PY 2012
VL 7
IS 2
AR e32022
DI 10.1371/journal.pone.0032022
PG 7
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 926ZM
UT WOS:000302873700135
PM 22363789
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Marrugo, AG
   Sorel, M
   Sroubek, F
   Millan, MS
AF Marrugo, Andres G.
   Sorel, Michal
   Sroubek, Filip
   Millan, Maria S.
TI Retinal image restoration by means of blind deconvolution
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE blind deconvolution; image restoration; deblurring; retinal image
ID DIABETIC-RETINOPATHY; ALGORITHMS; ROBUST; VIEW
AB Retinal imaging plays a key role in the diagnosis and management of ophthalmologic disorders, such as diabetic retinopathy, glaucoma, and age-related macular degeneration. Because of the acquisition process, retinal images often suffer from blurring and uneven illumination. This problem may seriously affect disease diagnosis and progression assessment. Here we present a method for color retinal image restoration by means of multichannel blind deconvolution. The method is applied to a pair of retinal images acquired within a lapse of time, ranging from several minutes to months. It consists of a series of preprocessing steps to adjust the images so they comply with the considered degradation model, followed by the estimation of the point-spread function and, ultimately, image deconvolution. The preprocessing is mainly composed of image registration, uneven illumination compensation, and segmentation of areas with structural changes. In addition, we have developed a procedure for the detection and visualization of structural changes. This enables the identification of subtle developments in the retina not caused by variation in illumination or blur. The method was tested on synthetic and real images. Encouraging experimental results show that the method is capable of significant restoration of degraded retinal images. (C) 2011 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.3652709]
C1 [Marrugo, Andres G.; Millan, Maria S.] Univ Politecn Cataluna, Dept Opt & Optometry, Grp Appl Opt & Image Proc, Barcelona 08222, Spain.
   [Sorel, Michal; Sroubek, Filip] Acad Sci Czech Republ, Inst Informat Theory & Automat, CR-18208 Prague 8, Czech Republic.
C3 Universitat Politecnica de Catalunya; Czech Academy of Sciences;
   Institute of Information Theory & Automation of the Czech Academy of
   Sciences
RP Marrugo, AG (通讯作者)，Univ Politecn Cataluna, Dept Opt & Optometry, Grp Appl Opt & Image Proc, Violinista Vellsola 37, Barcelona 08222, Spain.
EM andres.marrugo@upc.edu
RI Millán García-Varela, María Sagrario S./F-7250-2016; Marrugo,
   Andres/J-9151-2019; Marrugo, Andres G/F-8302-2016; Sorel,
   Michal/H-7949-2014; Sroubek, Filip/G-6882-2014
OI Millán García-Varela, María Sagrario S./0000-0001-6950-2373; Marrugo,
   Andres/0000-0003-2413-7645; Marrugo, Andres G/0000-0003-2413-7645;
   Sroubek, Filip/0000-0001-6835-4911; Marrugo Hernandez,
   Andres/0000-0001-7833-9969
FU Spanish Ministerio de Ciencia e Innovacion y Fondos FEDER
   [DPI2009-08879]; Czech Ministry of Education (Research Center DAR)
   [1M0572]; Spanish Ministerio de Educacion
FX This research has been partly funded by the Spanish Ministerio de
   Ciencia e Innovacion y Fondos FEDER (Project No. DPI2009-08879).
   Financial support was also provided by the Czech Ministry of Education
   under the Project No. 1M0572 (Research Center DAR). The authors are also
   grateful to the ophthalmologist Jordi Mones, M. D., from the Institut de
   la Macula i la Retina, Barcelona, for providing the images. The first
   author also thanks the Spanish Ministerio de Educacion for an FPU
   doctoral scholarship.
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NR 39
TC 36
Z9 36
U1 0
U2 12
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 1083-3668
EI 1560-2281
J9 J BIOMED OPT
JI J. Biomed. Opt.
PD NOV
PY 2011
VL 16
IS 11
AR 116016
DI 10.1117/1.3652709
PG 11
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
   Medical Imaging
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
   Medical Imaging
GA 868SU
UT WOS:000298546500023
PM 22112121
OA Bronze
DA 2022-11-30
ER

PT J
AU Kaufman, Y
   Ma, L
   Washington, I
AF Kaufman, Yardana
   Ma, Li
   Washington, Ilyas
TI Deuterium Enrichment of Vitamin A at the C20 Position Slows the
   Formation of Detrimental Vitamin A Dimers in Wild-type Rodents
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; LIPOFUSCIN FLUOROPHORE; MOUSE MODEL; MACULAR
   DEGENERATION; VISUAL CYCLE; A2E; ACCUMULATION; INHIBITION; RPE;
   COMPONENT
AB Degenerative eye diseases are the most common causes of untreatable blindness. Accumulation of lipofuscin (granular deposits) in the retinal pigment epithelium (RPE) is a hallmark of major degenerative eye diseases such as Stargardt disease, Best disease, and age-related macular degeneration. The intrinsic reactivity of vitamin A leads to its dimerization and to the formation of pigments such as A2E, and is believed to play a key role in the formation of ocular lipofuscin. We sought a clinically pragmatic method to slow vitamin A dimerization as a means to elucidate the pathogenesis of macular degenerations and to develop a therapeutic intervention. We prepared vitamin A enriched with the stable isotope deuterium at carbon twenty (C20-D-3-vitamin A). Results showed that dimerization of deuterium-enriched vitamin A was considerably slower than that of vitamin A at natural abundance as measured in vitro. Administration of C20-D-3-vitamin A to wild-type rodents with no obvious genetic defects in vitamin A processing, slowed A2E biosynthesis. This study elucidates the mechanism of A2E biosynthesis and suggests that administration of C20-D-3-vitamin A may be a viable, long-term approach to retard vitamin A dimerization and by extension, may slow lipofuscin deposition and the progression of common degenerative eye diseases.
C1 [Kaufman, Yardana; Ma, Li; Washington, Ilyas] Columbia Univ, Med Ctr, Dept Ophthalmol, New York, NY 10032 USA.
C3 Columbia University
RP Washington, I (通讯作者)，Columbia Univ, Med Ctr, Dept Ophthalmol, New York, NY 10032 USA.
EM iw2101@columbia.edu
OI W, I/0000-0002-2238-7918
FU International Retinal Research Foundation; NATIONAL EYE INSTITUTE
   [R01EY021207] Funding Source: NIH RePORTER
FX This work was supported by the International Retinal Research
   Foundation.
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NR 51
TC 41
Z9 51
U1 0
U2 3
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 11
PY 2011
VL 286
IS 10
BP 7958
EP 7965
DI 10.1074/jbc.M110.178640
PG 8
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 730DQ
UT WOS:000288013300026
PM 21075840
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Lim, SH
   Nowak-Sliwinska, P
   Kamarulzaman, FA
   van den Bergh, H
   Wagnieres, G
   Lee, HB
AF Lim, Siang Hui
   Nowak-Sliwinska, Patrycja
   Kamarulzaman, Fadzly Adzhar
   van den Bergh, Hubert
   Wagnieres, Georges
   Lee, Hong Boon
TI The Neovessel Occlusion Efficacy of 151-Hydroxypurpurin-7-Lactone
   Dimethyl Ester Induced with Photodynamic Therapy
SO PHOTOCHEMISTRY AND PHOTOBIOLOGY
LA English
DT Article
ID CHORIOALLANTOIC MEMBRANE CAM; IN-VIVO EVALUATION; PHOTOSENSITIZER;
   DELIVERY; CANCER; PDT; NANOPARTICLES; PRINCIPLES; PARAMETERS
AB In this study, the photodynamic therapy (PDT) induced efficacy of a semi-synthesized analogue 151-hydroxypurpurin-7-lactone dimethyl ester or G2, in terms of chick chorioallantoic membrane blood vessel occlusion was evaluated in reference to verteporfin. Early formulation studies showed that G2 prepared in a system of cremophor EL 2.5% and ethanol 2.5% in saline was biocompatible up to 20 mu L volume of injection. Following injection, G2 accumulation peaked within the first minute and its extravasation from intra- to extra-vascular occurred somewhat slower as compared with verteporfin. In the PDT study, closure of capillaries and small neovessels was observed with 4 mu g per embryo of G2 and a light dose of 20 J cm-2 at a fluence rate of 40 mW cm-2 filtered at 400-440 nm-a result that may be considered optimum for the treatment of age-related macular degeneration (AMD). Also, partial occlusion of the large vessels was observed using the same dose of G2 and light-an effect which is desirable for cancer treatment. From this study, we conclude that G2 has the potential to be developed as a therapeutic agent for photodynamic treatment for AMD and cancer.
C1 [Lim, Siang Hui; Kamarulzaman, Fadzly Adzhar; Lee, Hong Boon] Sime Darby Med Ctr, CARIF, Subang Jaya, Selangor, Malaysia.
   [Nowak-Sliwinska, Patrycja; van den Bergh, Hubert; Wagnieres, Georges] Ecole Polytech Fed Lausanne, Swiss Fed Inst Technol, Med Photon Grp, Inst Bioengn, CH-1015 Lausanne, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; Ecole Polytechnique
   Federale de Lausanne
RP Lee, HB (通讯作者)，Sime Darby Med Ctr, CARIF, Subang Jaya, Selangor, Malaysia.
EM hongboon.lee@carif.com.my
RI Lim, Siang Hui/H-2804-2014; Nowak-Sliwinska, Patrycja/T-7663-2018
OI Nowak-Sliwinska, Patrycja/0000-0002-8299-0444; ,
   LEE/0000-0002-0768-2222; Wagnieres, Georges/0000-0002-9082-3099
FU Malaysian Ministry of Science, Technology and Innovation (MOSTI); Cancer
   Research Initiatives Foundation (CARIF)
FX This work has been supported in part by Malaysian Ministry of Science,
   Technology and Innovation (MOSTI) and Cancer Research Initiatives
   Foundation (CARIF).
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NR 29
TC 27
Z9 27
U1 0
U2 7
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 MAR-APR
PY 2010
VL 86
IS 2
BP 397
EP 402
DI 10.1111/j.1751-1097.2009.00684.x
PG 6
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 563DM
UT WOS:000275107700022
PM 20074086
DA 2022-11-30
ER

PT J
AU Wang, Q
   Wang, PF
   Li, SQ
   Xiao, XS
   Jia, XY
   Guo, XM
   Kong, QP
   Yao, YG
   Zhang, QJ
AF Wang, Qin
   Wang, Panfeng
   Li, Shiqiang
   Xiao, Xueshan
   Jia, Xiaoyun
   Guo, Xiangming
   Kong, Qing-Peng
   Yao, Yong-Gang
   Zhang, Qingjiong
TI Mitochondrial DNA haplogroup distribution in Chaoshanese with and
   without myopia
SO MOLECULAR VISION
LA English
DT Article
ID HEREDITARY OPTIC NEUROPATHY; LIPID-PEROXIDATION PRODUCTS;
   HYPERBARIC-OXYGEN THERAPY; RECESSIVE HIGH MYOPIA; OXIDATIVE STRESS;
   CLINICAL EXPRESSION; MTDNA DATA; DISEASE; CHINESE; LOCUS
AB Purpose: Mitochondrial DNA (mtDNA) haplogroups affect the clinical expression of Leber hereditary optic neuropathy, age-related macular degeneration, and other diseases. The objective of this study is to investigate whether an mtDNA background is associated with myopia.
   Methods: Blood DNA was obtained from 192 college students, including 96 individuals with moderate-to-high myopia and 96 controls without myopia. All the subjects were from a well-known isolated population living in the Chaoshan area of east Guangdong Province and speaking one of the four major dialects in southern China. The mtDNA haplogroups in the 192 subjects were determined by sequencing the mtDNA control region and partial coding regions as well as by analysis of restriction fragment length polymorphisms. Each mtDNA was classified according to the updated version of the Eastern Asian haplogroup system.
   Results: Sixteen mtDNA haplogroups were recognized in the 192 subjects. The overall matrilineal structures of the samples with and without myopia were similar and had genetic imprints showing their ethno-origin. There was no statistical difference in frequencies of haplogroup distribution between subjects with and without myopia (chi(2) test, p = 0.556).
   Conclusions: We failed to identify clues that suggest an involvement of mtDNA background in the predisposition to myopia.
C1 [Wang, Qin; Wang, Panfeng; Li, Shiqiang; Xiao, Xueshan; Jia, Xiaoyun; Guo, Xiangming; Zhang, Qingjiong] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China.
   [Kong, Qing-Peng] Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming, Yunnan Province, Peoples R China.
   [Yao, Yong-Gang] Chinese Acad Sci, Key Lab Anim Models & Human Dis Mech, Kunming, Yunnan Province, Peoples R China.
C3 Sun Yat Sen University; Chinese Academy of Sciences; Kunming Institute
   of Zoology; Chinese Academy of Sciences
RP Zhang, QJ (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, 54 Xianlie Rd, Guangzhou 510060, Guangdong, Peoples R China.
EM qingjiongzhang@yahoo.com
RI Zhang, Qingjiong/AAR-6331-2021; Yao, Yong-Gang/AAH-2303-2021
OI Zhang, Qingjiong/0000-0001-7508-848X; Yao, Yong-Gang/0000-0002-2955-0693
FU National Natural Science Foundation of China [30725044]
FX The authors thank all subjects for their participation and Mr. Wen-Zhi
   Wang for helpful assistance with the data analysis. This study was
   supported in part by grants (30725044) from the National Natural Science
   Foundation of China.
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NR 38
TC 50
Z9 50
U1 0
U2 7
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD FEB 26
PY 2010
VL 16
IS 36
BP 303
EP 309
PG 7
WC Biochemistry & Molecular Biology; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Ophthalmology
GA 570ZQ
UT WOS:000275717800001
PM 20208987
DA 2022-11-30
ER

PT J
AU Honda, S
   Nagai, T
   Kondo, N
   Fukuda, M
   Kusuhara, S
   Tsukahara, Y
   Negi, A
AF Honda, Shigeru
   Nagai, Takayuki
   Kondo, Naoshi
   Fukuda, Masahide
   Kusuhara, Sentaro
   Tsukahara, Yasutomo
   Negi, Akira
TI Therapeutic Effect of Oral Bisphosphonates on Choroidal
   Neovascularization in the Human Eye
SO JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; ANGIOGENESIS; ALENDRONATE; GROWTH; RANIBIZUMAB;
   BEVACIZUMAB; ACTIVATION; STRATEGIES; INHIBITORS
AB Purpose. Choroidal neovascularization (CNV) is often associated with age-related macular degeneration (AMD) and pathological myopia (PM). Bisphosphonates, the drug of choice to treat osteoporosis, have been recently reported to have anti-angiogenic effects. The purpose of this study is to investigate the therapeutic effects of oral bisphosphonates for CNV in humans. Methods. Thirty-six consecutive cases with CNV due to AMD or PM who declined anti-VEGF therapy were recruited. The patients were prescribed 5 mg of oral alendronates daily for 6 months. The best-corrected visual-acuity (BCVA), the lesion size in fundus photographs and fluorescein angiography, foveal thickness and total macular volume in optical coherence tomography were compared between pre- and post-treatment. Results. The mean BCVA of the patients was significantly improved after a months with the treatment in the AMD group. In the PM group, the mean BCVA was maintained up to 6 months with the treatment. The mean lesion size was significantly decreased by 3 months in both groups. The averages of foveal thickness and total macular volume were significantly reduced after 1 month of treatment in the AMD group. Conclusions. Oral bisphosphonate should be further investigated as a possible therapeutic and preventive drug for CNV due to AMD and PM.
C1 [Honda, Shigeru; Nagai, Takayuki; Kondo, Naoshi; Fukuda, Masahide; Kusuhara, Sentaro; Tsukahara, Yasutomo; Negi, Akira] Kobe Univ, Grad Sch Med, Dept Surg, Div Ophthalmol, Kobe, Hyogo 6500017, Japan.
C3 Kobe University
RP Honda, S (通讯作者)，Kobe Univ, Grad Sch Med, Dept Surg, Div Ophthalmol, Kobe, Hyogo 6500017, Japan.
EM sighonda@med.kobe-u.ac.jp
RI Honda, Shigeru/W-4761-2019
OI Kusuhara, Sentaro/0000-0002-6458-539X
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NR 34
TC 17
Z9 17
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 2010
VL 2010
AR 206837
DI 10.1155/2010/206837
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA V24II
UT WOS:000208403700008
PM 20706646
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Jones, RPO
   Wang, MC
   Jowitt, TA
   Ridley, C
   Mellody, KT
   Howard, M
   Wang, T
   Bishop, PN
   Lotery, AJ
   Kielty, CM
   Baldock, C
   Trump, D
AF Jones, Richard P. O.
   Wang, Ming-Chuan
   Jowitt, Thomas A.
   Ridley, Caroline
   Mellody, Kieran T.
   Howard, Marjorie
   Wang, Tao
   Bishop, Paul N.
   Lotery, Andrew J.
   Kielty, Cay M.
   Baldock, Clair
   Trump, Dorothy
TI Fibulin 5 Forms a Compact Dimer in Physiological Solutions
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SMALL-ANGLE SCATTERING; CUTIS LAXA; IN-VIVO; HYDRODYNAMIC PROPERTIES;
   MACULAR DEGENERATION; PROTEIN INTERACTIONS; BINDING-PROTEIN; DOMAIN;
   DANCE/FIBULIN-5; FIBULIN-5/DANCE
AB Fibulin 5 is a 52-kDa calcium-binding epidermal growth factor (cbEGF)-rich extracellular matrix protein that is essential for the formation of elastic tissues. Missense mutations in fibulin 5 cause the elastin disorder cutis laxa and have been associated with age-related macular degeneration, a leading cause of blindness. We investigated the structure, hydrodynamics, and oligomerization of fibulin 5 using small angle x-ray scattering, EM, light scattering, circular dichroism, and sedimentation. Compact structures for the monomer were determined by small angle x-ray scattering and EM, and are supported by close agreement between the theoretical sedimentation of the structures and the experimental sedimentation of the monomer in solution. EM showed that monomers associate around a central cavity to form a dimer. Light scattering and equilibrium sedimentation demonstrated that the equilibrium between the monomer and the dimer is dependent upon NaCl and Ca2+ concentrations and that the dimer is dominant under physiological conditions. The dimerization of fragments containing just the cbEGF domains suggests that intermolecular interactions between cbEGFs cause dimerization of fibulin 5. It is possible that fibulin 5 functions as a dimer during elastinogenesis or that dimerization may provide a method for limiting interactions with binding partners such as tropoelastin.
C1 [Jones, Richard P. O.; Wang, Tao; Bishop, Paul N.; Trump, Dorothy] Univ Manchester, Fac Med & Human Sci, Manchester Acad Hlth Sci Ctr, Manchester M13 9PL, Lancs, England.
   [Wang, Ming-Chuan; Jowitt, Thomas A.; Ridley, Caroline; Mellody, Kieran T.; Howard, Marjorie; Bishop, Paul N.; Kielty, Cay M.; Baldock, Clair] Univ Manchester, Fac Life Sci, Wellcome Trust Ctr Cell Matrix Res, Manchester M13 9PL, Lancs, England.
   [Lotery, Andrew J.] Univ Southampton, Clin Neurosci Div, Southampton SO17 1BJ, Hants, England.
C3 University of Manchester; University of Manchester; University of
   Southampton
RP Trump, D (通讯作者)，Univ Manchester, St Marys Hosp, Manchester Acad Hlth Sci Ctr, Oxford Rd, Manchester M13 9WL, Lancs, England.
EM dorothy.trump@manchester.ac.uk
OI Baldock, Clair/0000-0003-3497-1959; Mellody, Kieran/0000-0002-8164-9148;
   Bishop, Paul/0000-0001-7937-7932; Jowitt, Thomas/0000-0002-4045-0933;
   Lotery, Andrew/0000-0001-5541-4305; Ridley, Caroline/0000-0002-5483-0320
FU Wellcome Trust [123364, 072291]; VIP award; National Institute for
   Health Research, Manchester Biomedical Research Centre; Medical Research
   Council [G0200246] Funding Source: researchfish; National Institute for
   Health Research [NF-SI-0507-10094] Funding Source: researchfish; MRC
   [G0200246] Funding Source: UKRI
FX This work was supported by Wellcome Trust Grants 123364 (to D. T., A. J.
   L., P. N. B., C. M. K., R. P. O. J., and C. R.), 072291 (to C. B. and M.
   C. W.), and VIP award (to R. P. O. J., and D. T.), and the National
   Institute for Health Research, Manchester Biomedical Research Centre.
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NR 47
TC 9
Z9 10
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD SEP 18
PY 2009
VL 284
IS 38
BP 25938
EP 25943
DI 10.1074/jbc.M109.011627
PG 6
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA 493LK
UT WOS:000269738000050
PM 19617354
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Sistiabudi, R
   Paderi, J
   Panitch, A
   Ivanisevic, A
AF Sistiabudi, Rizaldi
   Paderi, John
   Panitch, Alyssa
   Ivanisevic, Albena
TI Modification of Native Collagen With Cell-Adhesive Peptide to Promote
   RPE Cell Attachment on Bruch's Membrane
SO BIOTECHNOLOGY AND BIOENGINEERING
LA English
DT Article
DE cell attachment; collagen; retinal tissue; peptide; apoptosis
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; BETA-1 SUBUNIT;
   TRANSPLANTATION; LAYERS; PATHOGENESIS; INHIBITION; SCAFFOLDS; ETIOLOGY;
   TISSUE
AB Current efforts to reverse loss of visual function clue to Age-related Macular Degeneration point to the restoration of the Retinal Pigment Epithelial (RPE) layer. Restoration of the RPE layer involves replacing lost RPE cells as well as addressing the degeneration of the underlying Bruch's membrane (BM). To advance the potential of using donor BM, we present it strategy to achieve specific and controllable modification of the inner collagenous layer (ICL) of the Bruch's membrane. In particular, interaction between a collagen binding peptide (CBP) sequence with exposed collagen fibers oil the ICL Surface is utilized to anchor bioactive molecules. Here, a cell-adhesion sequence is added to the collagen binding sequence to promote attachment and survival of ARPE-19. First, the binding specificity of the CBP sequence is verified with a fluorescent binding assay. Subsequently, the effect of modification using the peptide is Studied qualitatively using confocal fluorescent imaging and quantitatively through a cell proliferation assay. Results of these experiments indicate that the peptide sequence binds specifically to collagen fibers. Additionally, modification using the peptide enhanced cell adhesion, allowing large uniform cell networks to be formed oil the surface, Furthermore, modification with the peptide also delayed the onset of apoptosis on adherent cells.
C1 [Sistiabudi, Rizaldi; Panitch, Alyssa; Ivanisevic, Albena] Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA.
   [Paderi, John] Arizona State Univ, Harrington Dept Bioengn, Tempe, AZ USA.
   [Ivanisevic, Albena] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
C3 Purdue University System; Purdue University; Purdue University West
   Lafayette Campus; Arizona State University; Arizona State
   University-Tempe; Purdue University System; Purdue University; Purdue
   University West Lafayette Campus
RP Ivanisevic, A (通讯作者)，Purdue Univ, Weldon Sch Biomed Engn, 206 S Martin Jischke Dr, W Lafayette, IN 47907 USA.
EM albena@purdue.edu
RI Sistiabudi, Rizaldi/AAR-6668-2020; Panitch, Alyssa/F-4413-2012
FU Weldon School of Biomedical Engineering, Purdue University, West
   Lafayette [IN 47907]
FX This work was supported by funding from the Weldon School of Biomedical
   Engineering, Purdue University, West Lafayette, IN 47907. We thank
   Steven Higbee and Kate Stuart for help with control experiments.
CR ALBERTS B, 2002, MOL BIOL CELL, P1104
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NR 28
TC 13
Z9 15
U1 0
U2 9
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-3592
EI 1097-0290
J9 BIOTECHNOL BIOENG
JI Biotechnol. Bioeng.
PD APR 15
PY 2009
VL 102
IS 6
BP 1723
EP 1729
DI 10.1002/bit.22215
PG 7
WC Biotechnology & Applied Microbiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology
GA 422MX
UT WOS:000264433500020
PM 19117272
DA 2022-11-30
ER

PT J
AU Maaijwee, K
   van den Biesen, PR
   van Meurs, JC
AF Maaijwee, K.
   van den Biesen, P. R.
   van Meurs, J. C.
TI Hyperfluorescence of the optic disc with indocyanine green angiography
SO EYE
LA English
DT Article
DE hyperfluorescence; ICG; indocyanine green angiography; macular surgery;
   optic disc
ID RETINAL-PIGMENT EPITHELIUM; MACULAR HOLE; FLUORESCENCE; FUNDUS; CAMERA
AB Purpose One-fourth of the patients with exudative age-related macular degeneration (AMD) treated with an autologous retinal pigment epithelium (RPE)-choroid translocation had a hyperfluorescent optic disc with indocyanine green angiography (ICGA). This study aimed to identify whether indocyanine green (ICG)-assisted surgery was related to the hyperfluorescence of the optic disc with ICGA.
   Methods Retrospective observational case series of 31 AMD patients treated with an RPE-choroid translocation and who had ICGA after surgery. The ICGAs were assessed for hypo/iso/hyperfluorescence of the optic disc and fluorescence was related to the time interval between ICGA and the possible use of intravitreal ICG.
   Results The optic disc was hyperfluorescent in six patients, isofluorescent in one, and hypofluorescent in 24 patients. All hyperfluorescent optic discs and 7 of the 24 hypofluorescent optic discs were preceded with ICG-assisted surgery with a time interval of 7 +/- 3 weeks and 43 +/- 12 weeks, respectively (P = 0.001, Student t-test). The other 17 hypofluorescent discs were not preceded by ICG-assisted surgery and the one isofluorescent optic disc was observed 32 weeks after ICG-assisted surgery.
   Conclusion There was a statistically significant correlation between intravitreal ICG use during surgery and a hyperfluorescent optic disc with ICGA in our patient group.
C1 [Maaijwee, K.; van Meurs, J. C.] Rotterdam Eye Hosp, NL-3011 BH Rotterdam, Netherlands.
   [van den Biesen, P. R.] Univ Med Ctr Utrecht, Dept Ophthalmol, Utrecht, Netherlands.
   [van Meurs, J. C.] Erasmus Univ, Rotterdam, Netherlands.
C3 Rotterdam Eye Hospital; Utrecht University; Utrecht University Medical
   Center; Erasmus University Rotterdam
RP Maaijwee, K (通讯作者)，Rotterdam Eye Hosp, Schiedamse Vest 180, NL-3011 BH Rotterdam, Netherlands.
EM kmaaijwee@hotmail.com
CR Flower RW, 1998, RETINA-J RET VIT DIS, V18, P260, DOI 10.1097/00006982-199803000-00012
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NR 9
TC 1
Z9 1
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD APR
PY 2009
VL 23
IS 4
BP 819
EP 821
DI 10.1038/eye.2008.146
PG 3
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 433QK
UT WOS:000265220700010
PM 18535607
OA Bronze
DA 2022-11-30
ER

PT J
AU Lu, B
   Malcuit, C
   Wang, SM
   Girman, S
   Francis, P
   Lemieux, L
   Lanza, R
   Lund, R
AF Lu, Bin
   Malcuit, Christopher
   Wang, Shaomei
   Girman, Sergej
   Francis, Peter
   Lemieux, Linda
   Lanza, Robert
   Lund, Raymond
TI Long-Term Safety and Function of RPE from Human Embryonic Stem Cells in
   Preclinical Models of Macular Degeneration
SO STEM CELLS
LA English
DT Article
DE Embryonic stem cells; Retinal pigment epithelium; Macular degeneration;
   Clinical trials
ID RETINAL-PIGMENT EPITHELIUM; RCS RAT; VISUAL FUNCTION; ROYAL-COLLEGE;
   TRANSPLANTATION; GENE; PHOTORECEPTORS; DYSTROPHY; SURVIVAL; MERTK
AB Assessments of safety and efficacy are crucial before human ESC (hESC) therapies can move into the clinic. Two important early potential hESC applications are the use of retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration and Stargardt disease, an untreatable form of macular dystrophy that leads to early-onset blindness. Here we show long-term functional rescue using hESC-derived RPE in both the RCS rat and Elov14 mouse, which are animal models of retinal degeneration and Stargardt, respectively. Good Manufacturing Practice-compliant hESC-RPE survived subretinal transplantation in RCS rats for prolonged periods (>220 days). The cells sustained visual function and photo-receptor integrity in a dose-dependent fashion without teratoma formation or untoward pathological reactions. Near-normal functional measurements were recorded at >60 days survival in RCS rats. To further address safety concerns, a Good Laboratory Practice-compliant study was carried out in the NIH III immune-deficient mouse model. Long-term data (spanning the life of the animals) showed no gross or microscopic evidence of teratoma/tumor formation after subretinal hESC-RPE transplantation. These results suggest that hESCs could serve as a potentially safe and inexhaustible source of RPE for the efficacious treatment of a range of retinal degenerative diseases. STEM CELLS 2009; 27: 2126-2135
C1 [Malcuit, Christopher; Lemieux, Linda; Lanza, Robert] Adv Cell Technol, Worcester, MA 01605 USA.
   [Lu, Bin; Wang, Shaomei; Girman, Sergej; Francis, Peter; Lund, Raymond] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97239 USA.
C3 Oregon Health & Science University
RP Lanza, R (通讯作者)，Adv Cell Technol, Worcester, MA 01605 USA.
EM rlanza@advancedcell.com; lundr@ohsu.edu
OI Lanza, Robert/0000-0002-3047-3074
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NR 30
TC 349
Z9 373
U1 1
U2 75
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 2009
VL 27
IS 9
BP 2126
EP 2135
DI 10.1002/stem.149
PG 10
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 497IX
UT WOS:000270053700009
PM 19521979
OA Bronze
DA 2022-11-30
ER

PT J
AU Mennel, S
   Barbazetto, I
   Meyer, CH
   Peter, S
   Stur, M
AF Mennel, Stefan
   Barbazetto, Irene
   Meyer, Carsten H.
   Peter, Silvia
   Stur, Michael
TI Ocular photodynamic therapy - Standard applications and new indications
   (part 2)
SO OPHTHALMOLOGICA
LA English
DT Review
DE ocular photodynamic therapy,children; macular degeneration; retinal
   astrocytic hamartoma; tuberous sclerosis; hemangioma, choroidal,
   capillary; von Hippel-Lindau disease; uveal melanoma; vasoproliferative
   tumor; squamous cell carcinoma; corneal neovascularizations
ID CENTRAL SEROUS CHORIORETINOPATHY; CIRCUMSCRIBED CHOROIDAL HEMANGIOMA;
   INDOCYANINE GREEN ANGIOGRAPHY; RETINAL CAPILLARY HEMANGIOMA;
   SQUAMOUS-CELL CARCINOMA; STURGE-WEBER-SYNDROME; MACULAR DEGENERATION;
   INTRAVITREAL TRIAMCINOLONE; VERTEPORFIN THERAPY; CORNEAL
   NEOVASCULARIZATION
AB Photodynamic therapy (PDT) has become a well-established treatment for vascular forms of age-related macular degeneration (AMD). The implementation of evidence-based medicine principles into the treatment regimen of AMD seems to be immensly important, since AMD continues to be the most frequent cause of blindness among patients older than 65 years in industrialized countries. Numerous randomized prospective studies demonstrated high levels of evidence for the efficacy of various treatment approaches such as laser photocoagulation, PDT, subretinal surgery or novel anti-angiogenic drugs [Arch Ophthalmol 2006; 124: 597-599]. The high evidence shown by these studies supported the rationale to use PDT also in additional, less frequent, vasoproliferative diseases. Although these 'case series' and 'individual case control studies' have a low level of evidence, they give us important information for treatment decisions in these rare conditions. The goal of this survey is to review the current literature regarding PDT in vasoproliferative and exudative ocular diseases outside AMD. Many studies modified the treatment parameters of PDT to address the specific pathology of the underlying disease. Table 1 summarizes the diseases and treatment parameters that are described in this part 2, the entire table of this review is included in part 1 (www.karger.com/doi/10.1159/000101922). Copyright (c) 2007 S. Karger AG, Basel.
C1 Univ Marburg, Dept Ophthalmol, DE-35037 Marburg, Germany.
   Univ Bonn, Dept Ophthalmol, D-5300 Bonn, Germany.
   Columbia Presbyterian Med Ctr, ES Harkness Eye Inst, New York, NY USA.
   Med Univ Vienna, Dept Ophthalmol, Vienna, Austria.
   Acad Hosp, Dept Ophthalmol, Feldkirch, Austria.
C3 Philipps University Marburg; University of Bonn; Columbia University;
   NewYork-Presbyterian Hospital; Medical University of Vienna
RP Mennel, S (通讯作者)，Univ Marburg, Dept Ophthalmol, Robert Koch Str 4, DE-35037 Marburg, Germany.
EM stefan.mennel@lycos.com
RI Meyer, Carsten/A-3981-2017
OI Meyer, Carsten/0000-0002-0530-5298
FU Medical Research Council [MR/J006742/1] Funding Source: Medline
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NR 76
TC 16
Z9 19
U1 0
U2 6
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3755
J9 OPHTHALMOLOGICA
JI Ophthalmologica
PY 2007
VL 221
IS 5
BP 282
EP 291
DI 10.1159/000104757
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 207BF
UT WOS:000249225900001
PM 17728549
DA 2022-11-30
ER

PT J
AU Page, WF
AF Page, William F.
TI Update on the NAS-NRC Twin Registry
SO TWIN RESEARCH AND HUMAN GENETICS
LA English
DT Article
ID ADULT MALE TWINS; ENVIRONMENTAL-INFLUENCES; DEPRESSIVE SYMPTOMS;
   SEX-HORMONES; RISK; HERITABILITY; DISEASE; HEART
AB The National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry is one of the oldest, national population-based twin registries in the United States. It consists of 15,924 white male twin pairs born in the years 1917 to 1927 (inclusive), both of whom served in the armed forces, mostly during World War II. This article updates activity in this registry since the earlier 2002 article in Twin Research. The results of clinically based studies on dementia, Parkinson's disease, age-related macular degeneration, and primary osteoarthritis were published, as well as articles based on previously collected questionnaire data on chronic fatigue syndrome, functional limitations, and healthy aging. In addition, risk factor studies are being planned to merge clinical data with earlier collected risk factor data from questionnaires. Examination data from the subset of National Heart, Lung, and Blood Institute (NHLBI) twins resulted in a number of articles, including the relationship of endogenous sex hormones to coronary heart disease and morphological changes in aging brain structures. The NEO Five-Factor Personality Inventory (a paper-and-pencil self-administered questionnaire) has been fielded for the first time. A push to consolidate the various data holdings of the registry is being made.
C1 Med Follow Up Agcy, Inst Med, Washington, DC 20001 USA.
RP Page, WF (通讯作者)，Med Follow Up Agcy, Inst Med, Keck 776,500 5th St NW, Washington, DC 20001 USA.
EM wpage@nas.edu
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NR 22
TC 5
Z9 5
U1 0
U2 1
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1832-4274
EI 1839-2628
J9 TWIN RES HUM GENET
JI Twin Res. Hum. Genet.
PD DEC
PY 2006
VL 9
IS 6
BP 985
EP 987
PG 3
WC Genetics & Heredity; Obstetrics & Gynecology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity; Obstetrics & Gynecology
GA 122HO
UT WOS:000243216600048
PM 17254441
DA 2022-11-30
ER

PT J
AU Landowski, M
   Bhute, VJ
   Takimoto, T
   Grindel, S
   Shahi, PK
   Pattnaik, BR
   Ikeda, S
   Ikeda, A
AF Landowski, Michael
   Bhute, Vijesh J.
   Takimoto, Tetsuya
   Grindel, Samuel
   Shahi, Pawan K.
   Pattnaik, Bikash R.
   Ikeda, Sakae
   Ikeda, Akihiro
TI A mutation in transmembrane protein 135 impairs lipid metabolism in
   mouse eyecups
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MACULAR DEGENERATION; APOLIPOPROTEIN-E; DIETARY-FAT; AGE; ASSOCIATION;
   GENE; CHOLESTEROL; SREBPS; RISK; SUSCEPTIBILITY
AB Aging is a significant factor in the development of age-related diseases but how aging disrupts cellular homeostasis to cause age-related retinal disease is unknown. Here, we further our studies on transmembrane protein 135 (Tmem135), a gene involved in retinal aging, by examining the transcriptomic profiles of wild-type, heterozygous and homozygous Tmem135 mutant posterior eyecup samples through RNA sequencing (RNA-Seq). We found significant gene expression changes in both heterozygous and homozygous Tmem135 mutant mouse eyecups that correlate with visual function deficits. Further analysis revealed that expression of many genes involved in lipid metabolism are changed due to the Tmem135 mutation. Consistent with these changes, we found increased lipid accumulation in mutant Tmem135 eyecup samples. Since mutant Tmem135 mice have similar ocular pathologies as human age-related macular degeneration (AMD) eyes, we compared our homozygous Tmem135 mutant eyecup RNA-Seq dataset with transcriptomic datasets of human AMD donor eyes. We found similar changes in genes involved in lipid metabolism between the homozygous Tmem135 mutant eyecups and AMD donor eyes. Our study suggests that the Tmem135 mutation affects lipid metabolism as similarly observed in human AMD eyes, thus Tmem135 mutant mice can serve as a good model for the role of dysregulated lipid metabolism in AMD.
C1 [Landowski, Michael; Bhute, Vijesh J.; Takimoto, Tetsuya; Grindel, Samuel; Shahi, Pawan K.; Pattnaik, Bikash R.; Ikeda, Sakae; Ikeda, Akihiro] Univ Wisconsin, Dept Med Genet, Madison, WI 53706 USA.
   [Landowski, Michael; Shahi, Pawan K.; Pattnaik, Bikash R.; Ikeda, Sakae; Ikeda, Akihiro] Univ Wisconsin, McPherson Eye Res Inst, Madison, WI 53706 USA.
   [Bhute, Vijesh J.] Imperial Coll London, Dept Chem Engn, London SW7 2AZ, England.
   [Shahi, Pawan K.; Pattnaik, Bikash R.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA.
C3 University of Wisconsin System; University of Wisconsin Madison;
   University of Wisconsin System; University of Wisconsin Madison;
   Imperial College London; University of Wisconsin System; University of
   Wisconsin Madison
RP Ikeda, A (通讯作者)，Univ Wisconsin, Dept Med Genet, Madison, WI 53706 USA.; Ikeda, A (通讯作者)，Univ Wisconsin, McPherson Eye Res Inst, Madison, WI 53706 USA.
EM aikeda@wisc.edu
FU University of Wisconsin Department of Pathology and Laboratory Medicine,
   UWCCC [P30 CA014520]; Office of the Director, National Institutes of
   Health [S10OD023526, NIH R01 EY022086, NIH T32EY027721, NIH F32EY032766,
   NIH P30 EY016665]; Research to Prevent Blindness, Inc.
FX We would like to thank Satoshi Kinoshita and the University of Wisconsin
   Translational tResearch Initiatives in Pathology laboratory (TRIP),
   supported by the University of Wisconsin Department of Pathology and
   Laboratory Medicine, UWCCC (P30 CA014520) and the Office of the
   Director, National Institutes of Health (S10OD023526) for the use of
   their services. Grants: NIH R01 EY022086, Timothy William Trout
   Chairmanship, NIH T32EY027721, NIH F32EY032766, NIH P30 EY016665 and
   Unrestricted Grant from Research to Prevent Blindness, Inc.
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NR 57
TC 1
Z9 1
U1 0
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 JAN 14
PY 2022
VL 12
IS 1
AR 756
DI 10.1038/s41598-021-04644-3
PG 14
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA YG8TL
UT WOS:000742753500033
PM 35031662
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Cui, YK
   Pan, L
   Lam, T
   Wen, CY
   Do, CW
AF Cui, Ying-kun
   Pan, Li
   Lam, Tim
   Wen, Chun-yi
   Do, Chi-wai
TI Mechanistic links between systemic hypertension and open angle glaucoma
SO CLINICAL AND EXPERIMENTAL OPTOMETRY
LA English
DT Review
DE Asystemic hypertension; glaucoma; Intraocular pressure; Ocular perfusion
   pressure
ID OCULAR PERFUSION-PRESSURE; VASCULAR RISK-FACTORS; CILIARY BLOOD-FLOW;
   TO-LUMEN RATIO; INTRAOCULAR-PRESSURE; AQUEOUS-HUMOR; OXIDATIVE STRESS;
   ENDOTHELIAL DYSFUNCTION; ARTERIAL-HYPERTENSION; RETINAL ARTERIOLES
AB Systemic hypertension or hypertension is a very common chronic age-related disease worldwide. It is typically characterised by a sustained elevation of blood pressure, particularly when the systolic blood pressure and/or diastolic blood pressure are of more than 140 mmHg and 90 mmHg, respectively. If hypertension is not well controlled, it may lead to an increased risk of stroke and heart attack. It has been shown that hypertension is linked to various ocular diseases, including cataract, diabetic retinopathy, age-related macular degeneration, and glaucoma. Glaucoma is the leading cause of irreversible blindness worldwide. Primary open angle glaucoma is the most common form of the disease and is usually characterised by an increase in intraocular pressure. This condition, together with normal tension glaucoma, constitutes open angle glaucoma. Systemic hypertension has been identified as a risk factor for open angle glaucoma. It is speculated that blood pressure is involved in the pathogenesis of open angle glaucoma by altering intraocular pressure or ocular blood flow, or both. Recent evidence has shown that both extremely high and low blood pressure are associated with increased risk of open angle glaucoma. Additional pathogenic mechanisms, including increased inflammation likely to be involved in the development and progression of these two diseases, are discussed.
C1 [Cui, Ying-kun; Pan, Li; Lam, Tim; Do, Chi-wai] Hong Kong Polytech Univ, Sch Optometry, Hong Kong, Peoples R China.
   [Wen, Chun-yi] Hong Kong Polytech Univ, Dept Biomed Engn, Hong Kong, Peoples R China.
   [Do, Chi-wai] Ctr Eye & Vis Res, Hong Kong, Peoples R China.
C3 Hong Kong Polytechnic University; Hong Kong Polytechnic University
RP Do, CW (通讯作者)，Hong Kong Polytech Univ, Sch Optometry, Hong Kong, Peoples R China.; Do, CW (通讯作者)，Ctr Eye & Vis Res, Hong Kong, Peoples R China.
EM chi-wai.do@polyu.edu.hk
RI WEN, Chunyi/P-4168-2017; Do, Chi Wai/M-4250-2017; PAN, Li/ABB-1237-2021
OI WEN, Chunyi/0000-0003-1949-7822; Do, Chi Wai/0000-0002-7720-7507; PAN,
   Li/0000-0002-4839-7057
FU Health Medical Research Fund [16172571]; PolyU Postgraduate
   Studentships; PolyU internal grants; Government of the Hong Kong Special
   Administrative Region & Innovation and Technology Fund
FX Health Medical Research Fund [Ref no. 16172571]; PolyU Postgraduate
   Studentships [Y.K.C and L.P]; PolyU internal grants [UAGF, UAHG]; The
   Government of the Hong Kong Special Administrative Region & Innovation
   and Technology Fund.
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NR 104
TC 0
Z9 0
U1 2
U2 3
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0816-4622
EI 1444-0938
J9 CLIN EXP OPTOM
JI Clin. Exp. Optom.
PD MAY 19
PY 2022
VL 105
IS 4
BP 362
EP 371
DI 10.1080/08164622.2021.1964332
EA AUG 2021
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 2O6KL
UT WOS:000685744500001
PM 34402761
DA 2022-11-30
ER

PT J
AU Pretto, C
   Tang, M
   Chen, M
   Xu, HP
   Subrizi, A
   Urtti, A
   van Hest, JCM
AF Pretto, Chiara
   Tang, Miao
   Chen, Mei
   Xu, Heping
   Subrizi, Astrid
   Urtti, Arto
   van Hest, Jan C. M.
TI Cowpea Chlorotic Mottle Virus-Like Particles as Potential Platform for
   Antisense Oligonucleotide Delivery in Posterior Segment Ocular Diseases
SO MACROMOLECULAR BIOSCIENCE
LA English
DT Article
DE antisense oligonucleotides; Cowpea chlorotic mottle virus; cross&#8208;
   linking; locked nucleic acid; miR&#8208; 23; transfection; virus&#8208;
   like particles
ID HETEROLOGOUS EXPRESSION; CAPSID PROTEIN; ANGIOGENESIS; SIRNA;
   NEOVASCULARIZATION; NANOPARTICLE; STABILITY
AB Due to its small size, easy accessibility and immune privileged environment, the eye represents an ideal target for therapeutic nucleic acids in the treatment of posterior segment ocular diseases, such as age-related macular degeneration (AMD). Among nanocarriers that can be used to achieve nucleic acid delivery, virus-like particles (VLPs) obtained from the Cowpea chlorotic mottle virus (CCMV) are an appealing platform, because of their loading capacity, ease of manufacture and amenability for functionalization. Herein, antisense oligonucleotide-loaded CCMV nanoparticles, intended for intravitreal injection, are evaluated for selective silencing of miR-23, an important target in AMD. CCMV nanoparticles loaded with anti-miR-23 locked nucleic acid and stabilized using the 3,3 '-dithiobis(sulfosuccinimidyl propionate) (DTSSP) cross-linker, are assembled in vitro with a loading efficiency up to 80%. VLPs are found to be stable at 37 degrees C in the vitreous humor up to 24 hours. Nanoparticle cytotoxicity, cellular uptake and transfection efficacy are evaluated in endothelial cells. Selective miRNA down-regulation is achieved by the loaded CCMV VLPs both in absence and presence of Lipofectamine, with efficacies of approximate to 40% and more than 80%, respectively. The authors' findings pave the way for the future development of CCMV nanoparticles as oligonucleotide delivery platform to treat posterior segment ocular diseases.
C1 [Pretto, Chiara; van Hest, Jan C. M.] Eindhoven Univ Technol, Inst Complex Mol Syst, Dept Biomed Engn, POB 513, NL-5600 MB Eindhoven, Netherlands.
   [Tang, Miao; Chen, Mei; Xu, Heping] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Welcome Wolfson Inst Expt Med, 97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland.
   [Subrizi, Astrid; Urtti, Arto] Univ Eastern Finland, Sch Pharm, Kuopio 70210, Finland.
C3 Eindhoven University of Technology; Queens University Belfast;
   University of Eastern Finland
RP van Hest, JCM (通讯作者)，Eindhoven Univ Technol, Inst Complex Mol Syst, Dept Biomed Engn, POB 513, NL-5600 MB Eindhoven, Netherlands.
EM J.C.M.v.Hest@tue.nl
RI Xu, Heping/A-4430-2008; van Hest, Jan/D-5625-2012
OI Xu, Heping/0000-0003-4000-931X; van Hest, Jan/0000-0001-7973-2404
FU European Union's Horizon 2020 research and innovation programme under
   the Marie Skodowska-Curie Grant [722717]
FX This project has received funding from the European Union's Horizon 2020
   research and innovation programme under the Marie Skodowska-Curie Grant
   Agreement No. 722717. The authors thank Suzanne Timmermans for the
   acquisition of the TEM images and Shirin Tavakoli for her help and
   guidance in the extraction of the vitreous humor from porcine eyes. The
   authors would also like to thank Suzanne Timmermans, Daan Vervoort, and
   Stephen Marry for the fruitful discussions.
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NR 51
TC 2
Z9 2
U1 3
U2 14
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1616-5187
EI 1616-5195
J9 MACROMOL BIOSCI
JI Macromol. Biosci.
PD AUG
PY 2021
VL 21
IS 8
AR 2100095
DI 10.1002/mabi.202100095
EA MAY 2021
PG 9
WC Biochemistry & Molecular Biology; Materials Science, Biomaterials;
   Polymer Science
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Materials Science; Polymer Science
GA UB5VZ
UT WOS:000653533800001
PM 34031995
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Yako, T
   Nakamura, M
   Nakamura, S
   Hara, H
   Shimazawa, M
AF Yako, Tomohiro
   Nakamura, Maho
   Nakamura, Shinsuke
   Hara, Hideaki
   Shimazawa, Masamitsu
TI Pharmacological inhibition of mitochondrial fission attenuates oxidative
   stress-induced damage of retinal pigmented epithelial cells
SO JOURNAL OF PHARMACOLOGICAL SCIENCES
LA English
DT Article
DE Age-related macular degeneration; Retinal pigment epithelium;
   Mitochondrial dynamics; Mitochondrial division inhibitor 1
ID COMPLEX-I INHIBITOR; MACULAR DEGENERATION; BIOGENESIS; MECHANISMS;
   MORPHOLOGY; DYNAMICS; THERAPY; AMD
AB Mitochondria maintain their function by the process of mitochondrial dynamics, which involves repeated fusion and fission. It is thought that the failure of mitochondrial dynamics, especially excessive fission, is related to the progression of several diseases. A previous study demonstrated that mitochondrial fragmentation occurs in the retinal pigmented epithelial (RPE) cells of patients with nonexudative age-related macular degeneration (AMD). We predicted that the suppression of mitochondrial fragmentation offers a novel therapeutic strategy for non-exudative AMD. We investigated whether the inhibition of mitochondrial fission was effective against the oxidative stress-induced damage of ARPE-19 cells. The treatment of ARPE-19 cells with H2O2 caused mitochondrial fragmentation, but treatment with mitochondrial division inhibitor 1 (Mdivi-1) suppressed fragmentation. Additionally, Mdivi-1 protected ARPE-19 cells against H2O2-induced damage, and suppressed the release of cytochrome c from the mitochondria. Mitochondrial function was evaluated by staining with JC-1 and measuring the production of reactive oxygen species (ROS), which revealed that mitochondrial function improved in the Mdivi-1-treated group. These findings indicated that the inhibition of mitochondrial fission would be a novel therapeutic target for non-exudative AMD. (C) 2021 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.
C1 [Yako, Tomohiro; Nakamura, Maho; Nakamura, Shinsuke; Hara, Hideaki; Shimazawa, Masamitsu] Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, Gifu, Japan.
C3 Gifu Pharmaceutical University
RP Shimazawa, M (通讯作者)，Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Mol Pharmacol, Gifu, Japan.
EM shimazawa@gifu-pu.ac.jp
OI Hara, Hideaki/0000-0003-2046-9001
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NR 54
TC 2
Z9 2
U1 0
U2 3
PU JAPANESE PHARMACOLOGICAL SOC
PI KYOTO
PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604,
   JAPAN
SN 1347-8613
EI 1347-8648
J9 J PHARMACOL SCI
JI J. Pharmacol. Sci.
PD JUL
PY 2021
VL 146
IS 3
BP 149
EP 159
DI 10.1016/j.jphs.2021.03.012
EA APR 2021
PG 11
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA SJ0XI
UT WOS:000655253000004
PM 34030797
OA gold
DA 2022-11-30
ER

PT J
AU Bigot, K
   Gondouin, P
   Benard, R
   Montagne, P
   Youale, J
   Piazza, M
   Picard, E
   Bordet, T
   Behar-Cohen, F
AF Bigot, Karine
   Gondouin, Pauline
   Benard, Romain
   Montagne, Pierrick
   Youale, Jenny
   Piazza, Marie
   Picard, Emilie
   Bordet, Thierry
   Behar-Cohen, Francine
TI Transferrin Non-Viral Gene Therapy for Treatment of Retinal Degeneration
SO PHARMACEUTICS
LA English
DT Article
DE iron; retinal degeneration; age-related macular degeneration; retinitis
   pigmentosa; transferrin; gene therapy; plasmid electrotransfection
ID METHYL-N-NITROSOUREA; CONE CELL-DEATH; PIGMENT EPITHELIAL-CELLS; RCS RAT
   MODEL; OXIDATIVE STRESS; LIGHT DAMAGE; PHOTORECEPTOR DEGENERATION;
   IRON-METABOLISM; MOUSE MODEL; ELECTROTRANSFER
AB Dysregulation of iron metabolism is observed in animal models of retinitis pigmentosa (RP) and in patients with age-related macular degeneration (AMD), possibly contributing to oxidative damage of the retina. Transferrin (TF), an endogenous iron chelator, was proposed as a therapeutic candidate. Here, the efficacy of TF non-viral gene therapy based on the electrotransfection of pEYS611, a plasmid encoding human TF, into the ciliary muscle was evaluated in several rat models of retinal degeneration. pEYS611 administration allowed for the sustained intraocular production of TF for at least 3 and 6 months in rats and rabbits, respectively. In the photo-oxidative damage model, pEYS611 protected both retinal structure and function more efficiently than carnosic acid, a natural antioxidant, reduced microglial infiltration in the outer retina and preserved the integrity of the outer retinal barrier. pEYS611 also protected photoreceptors from N-methyl-N-nitrosourea-induced apoptosis. Finally, pEYS611 delayed structural and functional degeneration in the RCS rat model of RP while malondialdehyde (MDA) ocular content, a biomarker of oxidative stress, was decreased. The neuroprotective benefits of TF non-viral gene delivery in retinal degenerative disease models further validates iron overload as a therapeutic target and supports the continued development of pEY611 for treatment of RP and dry AMD.
C1 [Bigot, Karine; Gondouin, Pauline; Benard, Romain; Montagne, Pierrick; Youale, Jenny; Piazza, Marie; Bordet, Thierry] Eyevensys, Biopk,11 Rue Watt, F-75013 Paris, France.
   [Youale, Jenny; Picard, Emilie; Behar-Cohen, Francine] Univ Paris 05, Sorbonne Univ, USPC, Ctr Rech Cordeliers,INSERM,Team 17, F-75006 Paris, France.
   [Behar-Cohen, Francine] Cochin Hosp, AP HP, Ophtalmopole, 24 Rue Faubourg St Jacques, F-75014 Paris, France.
C3 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 Cochin - APHP; UDICE-French Research Universities;
   Universite Paris Cite
RP Bordet, T (通讯作者)，Eyevensys, Biopk,11 Rue Watt, F-75013 Paris, France.; Behar-Cohen, F (通讯作者)，Univ Paris 05, Sorbonne Univ, USPC, Ctr Rech Cordeliers,INSERM,Team 17, F-75006 Paris, France.; Behar-Cohen, F (通讯作者)，Cochin Hosp, AP HP, Ophtalmopole, 24 Rue Faubourg St Jacques, F-75014 Paris, France.
EM karine.bigot@eyevensys.com; pauline.gondouin@eyevensys.com;
   romain.benard@eyevensys.com; pierrick.montagne@eyevensys.com;
   jenny.youale@eyevensys.com; marie.piazza@eyevensys.com;
   emilie.picard@crc.jussieu.fr; thierry.bordet@eyevensys.com;
   francine.behar-cohen@parisdescartes.fr
RI BORDET, THIERRY/AIA-7041-2022; picard, emilie/A-6919-2013
OI BORDET, THIERRY/0000-0002-3648-2270; Piazza, Marie/0000-0002-0952-2986;
   behar cohen, francine/0000-0001-8571-9513; picard,
   emilie/0000-0002-2689-0510
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NR 74
TC 7
Z9 7
U1 0
U2 2
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1999-4923
J9 PHARMACEUTICS
JI Pharmaceutics
PD SEP
PY 2020
VL 12
IS 9
AR 836
DI 10.3390/pharmaceutics12090836
PG 22
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA OE8WS
UT WOS:000580804500001
PM 32882879
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Ye, K
   Takemoto, Y
   Ito, A
   Onda, M
   Morimoto, N
   Mandai, M
   Takahashi, M
   Kato, R
   Osakada, F
AF Ye, Ke
   Takemoto, Yuto
   Ito, Arisa
   Onda, Masanari
   Morimoto, Nao
   Mandai, Michiko
   Takahashi, Masayo
   Kato, Ryuji
   Osakada, Fumitaka
TI Reproducible production and image-based quality evaluation of retinal
   pigment epithelium sheets from human induced pluripotent stem cells
SO SCIENTIFIC REPORTS
LA English
DT Article
ID DIRECTED DIFFERENTIATION; EYE DEVELOPMENT; LIVE-CELL; JUNCTIONS;
   INHIBITION; GENERATION; ADHERENS; PATHWAY; CULTURE
AB Transplantation of retinal pigment epithelial (RPE) sheets derived from human induced pluripotent cells (hiPSC) is a promising cell therapy for RPE degeneration, such as in age-related macular degeneration. Current RPE replacement therapies, however, face major challenges. They require a tedious manual process of selecting differentiated RPE from hiPSC-derived cells, and despite wide variation in quality of RPE sheets, there exists no efficient process for distinguishing functional RPE sheets from those unsuitable for transplantation. To overcome these issues, we developed methods for the generation of RPE sheets from hiPSC, and image-based evaluation. We found that stepwise treatment with six signaling pathway inhibitors along with nicotinamide increased RPE differentiation efficiency (RPE6iN), enabling the RPE sheet generation at high purity without manual selection. Machine learning models were developed based on cellular morphological features of F-actin-labeled RPE images for predicting transepithelial electrical resistance values, an indicator of RPE sheet function. Our model was effective at identifying low-quality RPE sheets for elimination, even when using label-free images. The RPE6iN-based RPE sheet generation combined with the non-destructive image-based prediction offers a comprehensive new solution for the large-scale production of pure RPE sheets with lot-to-lot variations and should facilitate the further development of RPE replacement therapies.
C1 [Ye, Ke; Ito, Arisa; Onda, Masanari; Morimoto, Nao; Osakada, Fumitaka] Nagoya Univ, Grad Sch Pharmaceut Sci, Lab Cellular Pharmacol, Nagoya, Aichi 4648601, Japan.
   [Takemoto, Yuto; Kato, Ryuji] Nagoya Univ, Grad Sch Pharmaceut Sci, Lab Cell & Mol Bioengn, Nagoya, Aichi 4648601, Japan.
   [Morimoto, Nao; Osakada, Fumitaka] Nagoya Univ, Inst Adv Res, Lab Neural Informat Proc, Nagoya, Aichi 4648601, Japan.
   [Mandai, Michiko; Takahashi, Masayo] RIKEN Ctr Biosyst Dynam Res, Lab Retinal Regenerat, Kobe, Hyogo 6500047, Japan.
   [Mandai, Michiko; Takahashi, Masayo] Kobe City Eye Hosp, Dept Opthalmol, Kobe, Hyogo 6500047, Japan.
   [Takahashi, Masayo] Vison Care Inc, Kobe, Hyogo 6500047, Japan.
   [Osakada, Fumitaka] Nagoya Univ, Inst Innovat Future Soc, Inst Nanolife Syst, Nagoya, Aichi 4648601, Japan.
   [Osakada, Fumitaka] Japan Sci & Technol Agcy, PRESTO CREST, Saitama 3320012, Japan.
C3 Nagoya University; Nagoya University; Nagoya University; RIKEN; Nagoya
   University; Japan Science & Technology Agency (JST)
RP Osakada, F (通讯作者)，Nagoya Univ, Grad Sch Pharmaceut Sci, Lab Cellular Pharmacol, Nagoya, Aichi 4648601, Japan.; Osakada, F (通讯作者)，Nagoya Univ, Inst Adv Res, Lab Neural Informat Proc, Nagoya, Aichi 4648601, Japan.; Osakada, F (通讯作者)，Nagoya Univ, Inst Innovat Future Soc, Inst Nanolife Syst, Nagoya, Aichi 4648601, Japan.; Osakada, F (通讯作者)，Japan Sci & Technol Agcy, PRESTO CREST, Saitama 3320012, Japan.
EM fosakada@ps.nagoya-u.ac.jp
RI Kato, Ryuji/I-6952-2014
OI Osakada, Fumitaka/0000-0002-9078-1458; KE, YE/0000-0002-9593-9007
FU Japan Society for the Promotion of Science; PRESTO from the Japan
   Science and Technology Agency; CREST from the Japan Science and
   Technology Agency; Mochida Memorial Foundation for Medical and
   Pharmaceutical Research; Suzuken Memorial Foundation; Kanae Foundation
   for the Promotion of Medical Science; Naito Foundation; Astellas
   Foundation for Research on Metabolic Disorders; Hokuto Foundation for
   Bioscience; Takeda Science Foundation; Novartis Pharma Grants for Basic
   Research; Japanese Retinitis Pigmentosa Society
FX We thank members of the Osakada laboratory for stimulating discussions;
   Drs. Masato Nakagawa and Shinya Yamanaka (Kyoto University) for the
   hiPSC lines; Noriko Sakai and Yumiko Shibata for hiPSC-RPE sheet
   production. This work was supported by Grants-in-Aid from the Japan
   Society for the Promotion of Science (F.O.), PRESTO and CREST from the
   Japan Science and Technology Agency (F.O.), the Mochida Memorial
   Foundation for Medical and Pharmaceutical Research (F.O.), the Suzuken
   Memorial Foundation (F.O.), the Kanae Foundation for the Promotion of
   Medical Science (F.O.), the Naito Foundation (F.O.), the Astellas
   Foundation for Research on Metabolic Disorders (F.O.), the Hokuto
   Foundation for Bioscience (F.O.), the Takeda Science Foundation (F.O.),
   the Novartis Pharma Grants for Basic Research (F.O.), and the Japanese
   Retinitis Pigmentosa Society (F.O.).
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NR 61
TC 11
Z9 11
U1 1
U2 4
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD SEP 1
PY 2020
VL 10
IS 1
AR 14387
DI 10.1038/s41598-020-70979-y
PG 15
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA NQ9ZA
UT WOS:000571223300004
PM 32873827
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Minami, S
   Nagai, N
   Suzuki, M
   Uchida, A
   Shinoda, H
   Tsubota, K
   Ozawa, Y
AF Minami, Sakiko
   Nagai, Norihiro
   Suzuki, Misa
   Uchida, Atsuro
   Shinoda, Hajime
   Tsubota, Kazuo
   Ozawa, Yoko
TI Ocular and Systemic Effects of Antioxidative Supplement Use in Young and
   Healthy Adults: Real-World Cross-Sectional Data
SO ANTIOXIDANTS
LA English
DT Article
DE antioxidative supplement; visual acuity; hs-CRP; cholesterol; HbA1c
ID FUNCTIONAL VISUAL-ACUITY; C-REACTIVE PROTEIN; MACULAR DEGENERATION;
   BILBERRY EXTRACT; VITAMIN-D; DRY EYE; HS-CRP; ASSOCIATION; DISEASE;
   VISION
AB Randomized controlled studies have shown that antioxidative supplements are effective in suppressing the progression of age-related macular degeneration and visual display terminal syndrome. However, effects of their general use in the real-world and by young and healthy individuals have not been well documented. We analyzed 27 participants who were under 35 years of age and had no diagnosed diseases. Mean functional visual acuity (FVA) score and visual maintenance ratio, which represent quick recognition of a target, both measured using FVA system, were better (bothp< 0.01) in subjects who had had regular antioxidative supplement intake for more than 2 months (11 participants) compared with those who had not. Systemic data, i.e., total cholesterol, hemoglobin A1c (HbA1c), and high-sensitivity C-reactive protein (hs-CRP) levels, which correspond to chronic low-grade inflammation, were lower (allp< 0.05) in the former. Overall, hs-CRP levels had a correlation with total cholesterol (p< 0.05) and a trend of correlation with HbA1c (p= 0.054) levels. Thus, current real-world data showed that young, healthy participants who had a regular intake of antioxidative supplements had better visual acuity and systemic levels of metabolic and low-grade inflammation markers. This study will help promote future research into the effects of general antioxidative supplement use.
C1 [Minami, Sakiko; Nagai, Norihiro; Suzuki, Misa; Uchida, Atsuro; Shinoda, Hajime; Tsubota, Kazuo; Ozawa, Yoko] Keio Univ, Dept Ophthalmol, Sch Med, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan.
   [Nagai, Norihiro; Suzuki, Misa; Ozawa, Yoko] Keio Univ, Lab Retinal Cell Biol, Sch Med, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan.
   [Ozawa, Yoko] St Lukes Int Hosp, Dept Ophthalmol, Chuo Ku, 9-1 Akashi Cho, Tokyo 1048560, Japan.
   [Ozawa, Yoko] St Lukes Int Univ, Chuo Ku, 9-1 Akashi Cho, Tokyo 1048560, Japan.
C3 Keio University; Keio University; St. Luke's International Hospital; St.
   Luke's International Hospital
RP Ozawa, Y (通讯作者)，Keio Univ, Dept Ophthalmol, Sch Med, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan.; Ozawa, Y (通讯作者)，Keio Univ, Lab Retinal Cell Biol, Sch Med, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan.; Ozawa, Y (通讯作者)，St Lukes Int Hosp, Dept Ophthalmol, Chuo Ku, 9-1 Akashi Cho, Tokyo 1048560, Japan.; Ozawa, Y (通讯作者)，St Lukes Int Univ, Chuo Ku, 9-1 Akashi Cho, Tokyo 1048560, Japan.
EM saki.love5@icloud.com; nagai@a5.keio.jp; misa.suzuki@suzukiganka.com;
   uchidats@gmail.com; shinoha@mac.com; tsubota@z3.keio.jp;
   ozawa@a5.keio.jp
RI Uchida, Atsuro/GVT-8593-2022; Tsubota, Kazuo/M-1915-2013
OI Ozawa, Yoko/0000-0003-4797-5705; Tsubota, Kazuo/0000-0002-8874-7111
FU Wakasa Seikatsu Co. Ltd.
FX This research received a research grant fromWakasa Seikatsu Co. Ltd.
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NR 58
TC 0
Z9 0
U1 1
U2 2
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2076-3921
J9 ANTIOXIDANTS-BASEL
JI Antioxidants
PD JUN
PY 2020
VL 9
IS 6
AR 487
DI 10.3390/antiox9060487
PG 13
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Food Science &
   Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Food Science
   & Technology
GA MR9FU
UT WOS:000553895200001
PM 32503322
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Guan, JT
   Li, XX
   Peng, DW
   Zhang, WM
   Qu, J
   Lu, F
   D'Amato, RJ
   Chi, ZL
AF Guan, Ji-Tian
   Li, Xin-Xin
   Peng, De-Wei
   Zhang, Wen-Meng
   Qu, Jia
   Lu, Fan
   D'Amato, Robert J.
   Chi, Zai-Long
TI MicroRNA-18a-5p Administration Suppresses Retinal Neovascularization by
   Targeting FGF1 and HIF1A
SO FRONTIERS IN PHARMACOLOGY
LA English
DT Article
DE miR-18a-5p; neovascularization; proliferative retinopathy; FGF1; HIF1A
ID OXYGEN-INDUCED RETINOPATHY; ENDOTHELIAL GROWTH-FACTOR; NONCODING RNAS;
   FACTOR-I; ANGIOGENESIS; VEGF; HYPOXIA; EXPRESSION; CLUSTER; HIF-1-ALPHA
AB Pathologic ocular neovascularization commonly results in visual impairment or even blindness in numerous fundus diseases, including proliferative diabetic retinopathy (PDR), retinopathy of prematurity (ROP), and age-related macular degeneration (AMD). MicroRNAs regulate angiogenesis through modulating target genes and disease progression, making them a new class of targets for drug discovery. In this study, we investigated the potential role of miR-18a-5p in retinal neovascularization using a mouse model of oxygen-induced proliferative retinopathy (OIR). We found that miR-18a-5p was highly expressed in the retina of pups as well as retinal endothelial cells, and was consistently down-regulated during retinal development. On the other hand, miR-18a-5p was increased significantly during pathologic neovascularization in the retinas of OIR mice. Moreover, intravitreal administration of miRNA mimic, agomiR-18a-5p, significantly suppressed retinal neovascularization in OIR models. Accordingly, agomir-18a-5p markedly suppressed human retinal microvascular endothelial cell (HRMEC) function including proliferation, migration, and tube formation ability. Additionally, we demonstrated that miR-18a-5p directly down-regulated known vascular growth factors, fibroblast growth factor 1 (FGF1) and hypoxia-inducible factor 1-alpha (HIF1A), as the target genes. In conclusion, miR-18a-5p may be a useful drug target for pathologic ocular neovascularization.
C1 [Guan, Ji-Tian; Li, Xin-Xin; Peng, De-Wei; Zhang, Wen-Meng; Qu, Jia; Lu, Fan; Chi, Zai-Long] Wenzhou Med Univ, Hosp Eye, State Key Lab Ophthalmol Optometry & Visual Sci, Wenzhou, Peoples R China.
   [Lu, Fan; Chi, Zai-Long] Wenzhou Med Univ, Int Joint Res Ctr Regenerat Med & Neurogenet, Wenzhou, Peoples R China.
   [D'Amato, Robert J.] Boston Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA USA.
   [D'Amato, Robert J.] Harvard Med Sch, Dept Ophthalmol, Boston, MA 02115 USA.
C3 Wenzhou Medical University; Wenzhou Medical University; Harvard
   University; Boston Children's Hospital; Harvard University; Harvard
   Medical School
RP Chi, ZL (通讯作者)，Wenzhou Med Univ, Hosp Eye, State Key Lab Ophthalmol Optometry & Visual Sci, Wenzhou, Peoples R China.; Chi, ZL (通讯作者)，Wenzhou Med Univ, Int Joint Res Ctr Regenerat Med & Neurogenet, Wenzhou, Peoples R China.
EM zailong.chi@eye.ac.cn
RI Peng, Dewei/GYJ-4183-2022
FU National Natural Science Foundation of China [81770918]; Zhejiang
   ProvincialNatural Science Foundation of China [LY16H120006]
FX This research was supported by the National Natural Science Foundation
   of China (81770918) and Zhejiang ProvincialNatural Science Foundation of
   China (LY16H120006).
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NR 63
TC 12
Z9 12
U1 0
U2 4
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 1663-9812
J9 FRONT PHARMACOL
JI Front. Pharmacol.
PD MAR 10
PY 2020
VL 11
AR 276
DI 10.3389/fphar.2020.00276
PG 11
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA LE5QF
UT WOS:000526772900001
PM 32210827
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Vellakani, S
   Pushbam, I
AF Vellakani, Sivamurugan
   Pushbam, Indumathi
TI An enhanced OCT image captioning system to assist ophthalmologists in
   detecting and classifying eye diseases
SO JOURNAL OF X-RAY SCIENCE AND TECHNOLOGY
LA English
DT Article
DE Age-related macular degeneration (AMD); connective tissue; choroidal
   neovascularization (CNV); light sensitive tissue; Optical Coherence
   Tomography (OCT); deep learning; convolution neural network (CNN); long
   short term memory (LSTM); neovascular tissue; surrounding tissue
AB Human eye is affected by the different eye diseases including choroidal neovascularization (CNV), diabetic macular edema (DME) and age-related macular degeneration (AMD). This work aims to design an artificial intelligence (AI) based clinical decision support system for eye disease detection and classification to assist the ophthalmologists more effectively detecting and classifying CNV, DME and drusen by using the Optical Coherence Tomography (OCT) images depicting different tissues. The methodology used for designing this system involves different deep learning convolutional neural network (CNN) models and long short-term memory networks (LSTM). The best image captioning model is selected after performance analysis by comparing nine different image captioning systems for assisting ophthalmologists to detect and classify eye diseases. The quantitative data analysis results obtained for the image captioning models designed using DenseNet201 with LSTM have superior performance in terms of overall accuracy of 0.969, positive predictive value of 0.972 and true-positive rate of 0.969using OCT images enhanced by the generative adversarial network (GAN). The corresponding performance values for the Xception with LSTM image captioning models are 0.969, 0.969 and 0.938, respectively. Thus, these two models yield superior performance and have potential to assist ophthalmologists in making optimal diagnostic decision.
C1 [Vellakani, Sivamurugan] Anna Univ, Dept Informat Technol, SSN Coll Engn, Chennai, Tamil Nadu, India.
   [Pushbam, Indumathi] Anna Univ, Dept Elect Engn, MIT Campus, Chennai, Tamil Nadu, India.
C3 Anna University; Anna University Chennai; SSN College of Engineering;
   Anna University; Anna University Chennai
RP Vellakani, S (通讯作者)，Anna Univ, Dept Informat Technol, SSN Coll Engn, Chennai, Tamil Nadu, India.
EM vsivamuruganssn@gmail.com
RI VELLAKANI, SIVAMURUGAN/ABD-8744-2021
FU SSN College of Engineering
FX This research was partially supported by SSN College of Engineering. We
   thank our colleagues from SSN College of Engineering who provided
   insight and expertise that greatly assisted the research, although they
   may not agree with all of the interpretations/conclusions of this paper.
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NR 16
TC 3
Z9 3
U1 9
U2 12
PU IOS PRESS
PI AMSTERDAM
PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS
SN 0895-3996
EI 1095-9114
J9 J X-RAY SCI TECHNOL
JI J. X-Ray Sci. Technol.
PY 2020
VL 28
IS 5
BP 975
EP 988
DI 10.3233/XST-200697
PG 14
WC Instruments & Instrumentation; Optics; Physics, Applied
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Instruments & Instrumentation; Optics; Physics
GA NV7LS
UT WOS:000574498800012
PM 32597828
DA 2022-11-30
ER

PT J
AU Kassa, E
   Ciulla, TA
   Hussain, RM
   Dugel, PU
AF Kassa, Enoch
   Ciulla, Thomas A.
   Hussain, Rehan M.
   Dugel, Pravin U.
TI Complement inhibition as a therapeutic strategy in retinal disorders
SO EXPERT OPINION ON BIOLOGICAL THERAPY
LA English
DT Review
DE Complement; age-related macular degeneration; geographic atrophy;
   lampalizumab; eculizumab; avacincaptad pegol; APL-2; LFG316; CL561;
   Stargardt macular dystrophy
ID STARGARDT DISEASE PROGSTAR; MEMBRANE ATTACK COMPLEX; VISUAL-ACUITY LOSS;
   MACULAR-DEGENERATION; ATROPHY SECONDARY; FACTOR-H; FUNDUS
   AUTOFLUORESCENCE; GEOGRAPHIC ATROPHY; PIGMENT EPITHELIUM; MOUSE MODEL
AB Introduction: Dry age-related macular degeneration (AMD) and Stargardt Macular Dystrophy (STGD1) result in vision loss due to progressive atrophy of the macula and lack of effective treatments. Numerous studies have implicated complement-associated inflammation as a contributor to both diseases. Areas covered: The complement factor D inhibitor, lampalizumab, failed to halt geographic atrophy (GA) progression in phase 3 studies. The complement factor 3 (C3) inhibitor, APL-2, has shown potential to reduce GA growth in a phase 2 trial, supporting advancement to phase 3 trials. The intravenous complement factor 5 (C5) inhibitor, eculizumab, failed to halt GA progression in a phase 2 study. Another C5 inhibitor, avacincaptad pegol, is delivered by intravitreal injection, and will be studied for safety and preliminary signs of efficacy for AMD and STGD1 patients in phase 2 trials. LFG316 (C5 inhibitor) and CLG561 (properdin inhibitor) failed to halt GA progression in phase 2 studies. A phase 1 trial is evaluating the effects of combining LFG316 and CL561. Complement inhibition by gene therapy will be explored in the phase 1 trial of HMR59 in AMD patients. Expert opinion: While complement inhibition has not yet demonstrated the ability to halt GA progression in a phase 3 trial, further study is warranted.
C1 [Kassa, Enoch] Indiana Univ Sch Med, Dept Ophthalmol, Indianapolis, IN 46202 USA.
   [Ciulla, Thomas A.] Midwest Eye Inst, Retina Serv, Indianapolis, IN USA.
   [Hussain, Rehan M.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, 900 NW 17th St, Miami, FL 33136 USA.
   [Dugel, Pravin U.] Retinal Consultants Arizona, Phoenix, AZ USA.
   [Dugel, Pravin U.] Univ Southern Calif, Keck Sch Med, USC Roski Eye Inst, Los Angeles, CA 90033 USA.
C3 Indiana University System; Indiana University Bloomington; Bascom Palmer
   Eye Institute; University of Miami; University of Southern California
RP Hussain, RM (通讯作者)，Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, 900 NW 17th St, Miami, FL 33136 USA.
EM rhussain27@med.miami.edu
RI Ciulla, Thomas/AAA-1299-2020
OI Ciulla, Thomas/0000-0001-5557-6777
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NR 64
TC 56
Z9 56
U1 1
U2 46
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1471-2598
EI 1744-7682
J9 EXPERT OPIN BIOL TH
JI Expert Opin. Biol. Ther.
PD APR 3
PY 2019
VL 19
IS 4
BP 335
EP 342
DI 10.1080/14712598.2019.1575358
PG 8
WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Research & Experimental Medicine
GA HW3EN
UT WOS:000466573300006
PM 30686077
DA 2022-11-30
ER

PT J
AU Jang, KH
   Do, YJ
   Koo, TS
   Choi, JS
   Song, EJ
   Hwang, Y
   Bae, HJ
   Lee, JH
   Kim, E
AF Jang, Ki-Hong
   Do, Yun-Ju
   Koo, Tae-Sung
   Choi, Jun-Sub
   Song, Eun Ju
   Hwang, Yeseong
   Bae, Hyun Ju
   Lee, Ju-hee
   Kim, Eunhee
TI Protective effect of RIPK1-inhibitory compound in in vivo models for
   retinal degenerative disease
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Dry AMD; Receptor interacting protein kinase1 (RIPK1); RIPK1-Inhibitory
   compound (RIC); Retinal degeneration; Topical application; RPE
   protection
ID RECEPTOR-INTERACTING PROTEIN; ISCHEMIA-REPERFUSION INJURY;
   KINASE-MEDIATED NECROSIS; CELL-DEATH; PIGMENT-EPITHELIUM; SODIUM IODATE;
   MACULAR DEGENERATION; PHOTORECEPTOR DEGENERATION; PROGRAMMED NECROSIS;
   BRUCHS MEMBRANE
AB Receptor interacting protein kinase 1 (RIPK1) plays a key role in necroptosis, which is a type of programmed necrosis that is involved in ocular diseases, including glaucoma and dry age-related macular degeneration (AMD). We previously introduced RIPK1-inhibitory compound (RIC), which has biochemical characteristics and a mode of action that are distinct from those of the prototype RIPK1 inhibitor necrostatin-1. The intraperitoneal administration of RIC exerts a protective effect on retinal ganglion cells against a glaucomatous insult. In this study, we examined the protective effect of RIC on retinal pigment epithelium (RPE) against sodium iodate (SI) insult, which is associated with dry AMD pathogenesis. The eye drop administration of RIC that reached on the retina prevented RPE loss in SI-induced retinal degeneration. RIC consistently demonstrated retinal protection in the funduscopy and electroretinogram analyses in SI-injected rabbits and iodoacetic acid-treated mini-pigs. Moreover, the in vivo protective effects of RIC were superior to those of ACU-4429 and doxycycline, which are other medications investigated in clinical trials for the treatment of dry AMD, and RIC did not induce retinal toxicity following topical administration in rats. Collectively, RIC displayed excellent retinal penetration and prevented retinal degeneration in the pathogenesis of dry AMD with a high in vivo efficacy.
C1 [Jang, Ki-Hong; Do, Yun-Ju; Hwang, Yeseong; Kim, Eunhee] Chungnam Natl Univ, Dept Biol Sci, 99 Deahak Ro, Daejeon, South Korea.
   [Koo, Tae-Sung] Chungnam Natl Univ, Grad Sch New Drug Discovery & Dev, Daejeon, South Korea.
   [Choi, Jun-Sub] Catholic Univ Korea, Catholic Inst Visual Sci, 505 Banpo Dong, Seoul, South Korea.
   [Song, Eun Ju] Ensol Biosci Inc, Dept Drug Dev, Technol Res Inst, Daejeon, South Korea.
   [Bae, Hyun Ju; Lee, Ju-hee] Kukjepharma R&D Ctr, Sanseong Ro 47, Ansan, Gyeonggi, South Korea.
   [Do, Yun-Ju] KoNECT Collaborat Ctr, 15F KPX,137, Seoul 04143, South Korea.
   [Choi, Jun-Sub] Cheongju Techno S Tower, Jikji Daero 530, Cheongju 28751, Chungbuk, South Korea.
C3 Chungnam National University; Chungnam National University; Catholic
   University of Korea
RP Kim, E (通讯作者)，Chungnam Natl Univ, Dept Biol Sci, 99 Deahak Ro, Daejeon, South Korea.
EM eunhee@cnu.ac.kr
RI Jang, Ki-Hong/AAR-2399-2021
OI Koo, Tae-Sung/0000-0001-8046-6836
FU National Research Foundation (NRF) - Korean government (MSIP)
   [NRF-2017M3A9C8021844]; chungnam National University
FX This study was supported by the Bio & Medical Technology Development
   Program of the National Research Foundation (NRF) funded by the Korean
   government (MSIP) (NRF-2017M3A9C8021844) and the fund from dispatch
   overseas program of chungnam National University in 2018.
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NR 64
TC 13
Z9 13
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 MAR
PY 2019
VL 180
BP 8
EP 17
DI 10.1016/j.exer.2018.11.026
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HN7KO
UT WOS:000460368500002
PM 30500363
DA 2022-11-30
ER

PT J
AU Cheung, CY
   Chan, VTT
   Mok, VC
   Chen, C
   Wong, TY
AF Cheung, Carol Y.
   Chan, Victor T. T.
   Mok, Vincent C.
   Chen, Christopher
   Wong, Tien Y.
TI Potential retinal biomarkers for dementia: what is new?
SO CURRENT OPINION IN NEUROLOGY
LA English
DT Review
DE Alzheimer's disease; biomarkers; dementia; retina
ID OPTICAL COHERENCE TOMOGRAPHY; OPEN-ANGLE GLAUCOMA; MILD COGNITIVE
   IMPAIRMENT; MICROVASCULAR NETWORK ALTERATIONS; VASCULAR FRACTAL
   DIMENSION; ALZHEIMERS-DISEASE; MACULAR DEGENERATION;
   DIABETIC-RETINOPATHY; EYE DISEASES; VISUAL IMPAIRMENT
AB Purpose of review
   To summarize the current findings on clinical retinal diseases and retinal imaging changes with dementia, focusing on Alzheimer's disease.
   Recent findings
   Studies observed that clinical retinal diseases such as age-related macular degeneration, open-angle glaucoma and diabetic retinopathy are related to dementia, but the associations are not entirely consistent. In terms of the retinal neuronal structure, multiple retinal neuronal layers are significantly thinner in Alzheimer's disease dementia, such as the parapapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GC-IPL). Recent studies further demonstrated that macular GC-IPL and macular RNFL are also significantly thinner in the preclinical stage of Alzheimer's disease. A thinner RNFL is also associated with a significantly increased risk of developing both cognitive decline and Alzheimer's disease dementia. In addition, studies consistently showed that retinal vascular changes are associated with poorer cognitive performance, as well as prevalent and incident Alzheimer's disease dementia.
   Summary
   The current findings support the concept that changes in the retina, particular in retinal neuronal structure and vasculature, can reflect the status of cerebral neuronal structure and vasculature, highlighting the potential role of retinal changes as biomarkers of dementia.
C1 [Cheung, Carol Y.; Chan, Victor T. T.] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong, Peoples R China.
   [Mok, Vincent C.] Chinese Univ Hong Kong, Gerald Choa Neurosci Ctr, Lui Che Woo Inst Innovat Med, Div Neurol,Dept Med & Therapeut, Hong Kong, Peoples R China.
   [Chen, Christopher] Natl Univ Hlth Syst, Memory Aging & Cognit Ctr, Singapore, Singapore.
   [Chen, Christopher] Natl Univ Singapore, Dept Pharmacol, Singapore, Singapore.
   [Wong, Tien Y.] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
   [Wong, Tien Y.] Natl Univ Singapore, Duke NUS Med Sch, Singapore, Singapore.
C3 Chinese University of Hong Kong; Chinese University of Hong Kong;
   National University of Singapore; National University of Singapore;
   National University of Singapore; Singapore National Eye Center;
   National University of Singapore
RP Cheung, CY (通讯作者)，Hong Kong Eye Hosp, CUHK Eye Ctr, Kowloon, 147K Argyle St, Hong Kong, Peoples R China.
EM carolcheung@cuhk.edu.hk
RI Wong, Tien Yin/AAC-9724-2020; Chen, Christopher/E-7023-2013; Cheung,
   Carol Y./G-7895-2016; Cheung, Carol/AAF-1101-2020; Mok,
   Vincent/N-6421-2015
OI Wong, Tien Yin/0000-0002-8448-1264; Chen,
   Christopher/0000-0002-1047-9225; Cheung, Carol/0000-0002-9672-1819; Mok,
   Vincent/0000-0002-8102-8835; Chan, Victor T.T./0000-0003-0930-5284
FU Health and Medical Research Fund, Hong Kong [04153506]; Bright Focus
   Foundation [A2018093S]; National Medical Research Council Singapore
   [NMRC/CG/NUHS/2010, NMRC/CG/013/2013]
FX Health and Medical Research Fund, Hong Kong (Grant Number: 04153506);
   Bright Focus Foundation (Reference Number: A2018093S); National Medical
   Research Council Singapore (NMRC/CG/NUHS/2010 and NMRC/CG/013/2013).
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NR 98
TC 27
Z9 27
U1 0
U2 16
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1350-7540
EI 1473-6551
J9 CURR OPIN NEUROL
JI Curr. Opin. Neurol.
PD FEB
PY 2019
VL 32
IS 1
BP 82
EP 91
DI 10.1097/WCO.0000000000000645
PG 10
WC Clinical Neurology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA HS3QJ
UT WOS:000463777100014
PM 30566412
DA 2022-11-30
ER

PT J
AU Chung, EJ
   Efstathiou, NE
   Konstantinou, EK
   Maidana, DE
   Miller, JW
   Young, LH
   Vavvas, DG
AF Chung, Eun Jee
   Efstathiou, Nikolaos E.
   Konstantinou, Eleni K.
   Maidana, Daniel E.
   Miller, Joan W.
   Young, Lucy H.
   Vavvas, Demetrios G.
TI AICAR suppresses TNF-alpha-induced complement factor B in RPE cells
SO SCIENTIFIC REPORTS
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; ACETYL-COA CARBOXYLASE; PIGMENT
   EPITHELIAL-CELLS; CARBOXAMIDE RIBONUCLEOTIDE AICAR; FACTOR-H
   POLYMORPHISM; 5-AMINOIMIDAZOLE-4-CARBOXAMIDE RIBOSIDE; GENE-EXPRESSION;
   UP-REGULATION; AMYLOID-BETA; PHOSPHORYLATION
AB Age related macular degeneration is the leading cause of blindness in the developed world. Although its precise cause remains elusive, dysfunction of the retinal pigment epithelium (RPE) and dysregulation of complement have been implicated in its pathogenesis. The goal of this study was to evaluate the role of an AMP-dependent kinase (AMPK) activator, 5-aminoimidazole-4-carboxamide riboside (AICAR), on tumor necrosis factor alpha (TNF-alpha) induction of complement factor B (CFB) in RPE cells. We found that AICAR inhibited TNF-alpha-induced CFB expression in ARPE-19 and human primary RPE cells in a dose-dependent fashion. Treatment of cells with dipyridamole, which blocks AICAR cellular uptake abolished these effects. In contrast, the adenosine kinase inhibitor, 5-iodotubericidin, which inhibits the conversion of AICAR to the direct activator of AMPK, ZMP, did not reverse the effects on TNF-alpha-induced CFB expression, suggesting AMPK-independent effects. Indeed, knockout of AMPK in RPE cells using Clustered Regularly Interspaced Palindromic Repeats (CRISPR)/Cas9 did not abolish the inhibitory effects of AICAR on RPE CFB expression. Collectively, our results suggest that AICAR can suppress TNF-alpha-induced CFB expression in RPE cells in an AMPK-independent mechanism, and could be used as a therapeutic target in certain complement over-activation scenarios.
C1 [Chung, Eun Jee; Efstathiou, Nikolaos E.; Konstantinou, Eleni K.; Maidana, Daniel E.; Miller, Joan W.; Young, Lucy H.; Vavvas, Demetrios G.] Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Retina Serv,Angiogenesis Lab, Boston, MA 02114 USA.
   [Chung, Eun Jee] Ilsan Hosp, Natl Hlth Insurance Serv, Dept Ophthalmol, Gyeonggi Do, South Korea.
C3 Harvard University; Harvard Medical School; Massachusetts Eye & Ear
   Infirmary; National Health Insurance Service; NHIS Ilsan Hospital
RP Vavvas, DG (通讯作者)，Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Retina Serv,Angiogenesis Lab, Boston, MA 02114 USA.
EM Demetrios_Vavvas@meei.harvard.edu
RI Konstantinou, Eleni/ABD-1753-2020
OI Miller, Joan/0000-0003-2046-3996; Vavvas, Demetrios/0000-0002-8622-6478;
   Young, Lucy/0000-0001-8634-7512; Chung, Eun Jee/0000-0001-8363-2836;
   Efstathiou, Nikolaos/0000-0002-6635-0391
FU Yeatts Family Foundation; Loefflers Family Fund; Macula Society Research
   Grant award; RPB; Alcon Research Institute Young Investigator Award;
   Research to Prevent Blindness foundation; STAMATIOU foundation
   scholarship; NEI [EY014104];  [NEI R21EY023079-01A1]; 
   [R01-EY025362-01]; NATIONAL EYE INSTITUTE [R01EY025362, P30EY014104,
   R21EY023079] Funding Source: NIH RePORTER
FX This work was supported by: NEI R21EY023079-01A1, R01-EY025362-01 (DGV);
   the Yeatts Family Foundation (DGV, JWM); the Loefflers Family Fund (DGV,
   JWM); the 2013 Macula Society Research Grant award (DGV); a Physician
   Scientist Award from RPB and the Alcon Research Institute Young
   Investigator Award (DGV), an unrestricted grant (JWM) from the Research
   to Prevent Blindness foundation; NEI grant EY014104 (MEEI Core Grant)
   and the STAMATIOU foundation scholarship (NEE).
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NR 52
TC 6
Z9 6
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD DEC 15
PY 2017
VL 7
AR 17651
DI 10.1038/s41598-017-17744-w
PG 8
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA FQ3IM
UT WOS:000418250800036
PM 29247196
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Sabeti, F
   James, AC
   Carle, CF
   Essex, RW
   Bell, A
   Maddess, T
AF Sabeti, Faran
   James, Andrew C.
   Carle, Corinne F.
   Essex, Rohan W.
   Bell, Andrew
   Maddess, Ted
TI Comparing multifocal pupillographic objective perimetry (mfPOP) and
   multifocal visual evoked potentials (mfVEP) in retinal diseases
SO SCIENTIFIC REPORTS
LA English
DT Article
ID ON-YELLOW PERIMETRY; MACULAR DEGENERATION; PUPILLARY RESPONSES;
   MULTIPLE-SCLEROSIS; DIABETIC-PATIENTS; FIELD DEFECTS; GLAUCOMA; STIMULI;
   COLOR; RETINOPATHY
AB Multifocal pupillographic objective perimetry (mfPOP) shows regions of slight hypersensitivity away from retinal regions damaged by diabetes or age-related macular degeneration (AMD). This study examines if such results also appear in multifocal visual evoked potentials (mfVEPs) recorded on the same day in the same patients. The pupil control system receives input from the extra-striate cortex, so we also examined evidence for such input. We recruited subjects with early type 2 diabetes (T2D) with no retinopathy, and patients with unilateral exudative AMD. Population average responses of the diabetes patients, and the normal fellow eyes of AMD patients, showed multiple regions of significant hypersensitivity (p < 0.05) on both mfPOP and mfVEPs. For mfVEPs the occipital electrodes showed fewer hypersensitive regions than the surrounding electrodes. More advanced AMD showed regions of suppression becoming centrally concentrated in the exudative AMD areas. Thus, mfVEP electrodes biased towards extra-striate cortical responses (surround electrodes) appeared to show similar hypersensitive visual field locations to mfPOP in early stage diabetic and AMD damage. Our findings suggest that hypersensitive regions may be a potential biomarker for future development of AMD or non-proliferative diabetic retinopathy, and may be more informative than visual acuity which remains largely undisturbed during early disease.
C1 [Sabeti, Faran; James, Andrew C.; Carle, Corinne F.; Bell, Andrew; Maddess, Ted] Australian Natl Univ, John Curtin Sch Med Res, Eccles Inst Neurosci, Canberra, ACT, Australia.
   [Sabeti, Faran; Essex, Rohan W.] Canberra Hosp, Dept Ophthalmol, Canberra, ACT, Australia.
   [Essex, Rohan W.] Australian Natl Univ, Med Sch, Canberra, ACT, Australia.
C3 Australian National University; John Curtin School of Medical Research;
   Australian National University; Canberra Hospital; Australian National
   University
RP Sabeti, F (通讯作者)，Australian Natl Univ, John Curtin Sch Med Res, Eccles Inst Neurosci, Canberra, ACT, Australia.; Sabeti, F (通讯作者)，Canberra Hosp, Dept Ophthalmol, Canberra, ACT, Australia.
EM faran.sabeti@anu.edu.au
RI Carle, Corinne/A-1729-2011; James, Andrew C/C-9307-2009; Maddess, Teddy
   L/A-3200-2008; Sabeti, Faran/AAR-1767-2021
OI Carle, Corinne/0000-0002-3309-9073; James, Andrew C/0000-0002-2447-8549;
   Maddess, Teddy L/0000-0003-4591-3658; SABETI, Faran/0000-0001-9187-7569;
   Essex, Rohan/0000-0001-5323-0334
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NR 38
TC 18
Z9 19
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD APR 3
PY 2017
VL 7
AR 45847
DI 10.1038/srep45847
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA FX2ER
UT WOS:000425872500001
PM 28368051
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU McCafferty, CL
   Sergeev, YV
AF McCafferty, Caitlyn L.
   Sergeev, Yuri V.
TI In silico Mapping of Protein Unfolding Mutations for Inherited Disease
SO SCIENTIFIC REPORTS
LA English
DT Article
ID DOMINANT RETINITIS-PIGMENTOSA; AMINO-ACID VARIANTS; RHODOPSIN GENE;
   OCULAR FINDINGS; PERSONALIZED MEDICINE; DISULFIDE-ISOMERASE; STABILITY
   CHANGES; MECHANISMS; CHALLENGES; SEQUENCE
AB The effect of disease-causing missense mutations on protein folding is difficult to evaluate. To understand this relationship, we developed the unfolding mutation screen (UMS) for in silico evaluation of the severity of genetic perturbations at the atomic level of protein structure. The program takes into account the protein-unfolding curve and generates propensities using calculated free energy changes for every possible missense mutation at once. These results are presented in a series of unfolding heat maps and a colored protein 3D structure to show the residues critical to the protein folding and are available for quick reference. UMS was tested with 16 crystal structures to evaluate the unfolding for 1391 mutations from the ProTherm database. Our results showed that the computational accuracy of the unfolding calculations was similar to the accuracy of previously published free energy changes but provided a better scale. Our residue identity control helps to improve protein homology models. The unfolding predictions for proteins involved in age-related macular degeneration, retinitis pigmentosa, and Leber's congenital amaurosis matched well with data from previous studies. These results suggest that UMS could be a useful tool in the analysis of genotype-to-phenotype associations and next-generation sequencing data for inherited diseases.
C1 [McCafferty, Caitlyn L.; Sergeev, Yuri V.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI)
RP Sergeev, YV (通讯作者)，NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
EM sergeevy@nei.nih.gov
FU NATIONAL EYE INSTITUTE [ZIAEY000476] Funding Source: NIH RePORTER
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NR 64
TC 15
Z9 15
U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD DEC 1
PY 2016
VL 6
AR 37298
DI 10.1038/srep37298
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA ED6UR
UT WOS:000388992600001
PM 27905547
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Temple, SE
   McGregor, JE
   Miles, C
   Graham, L
   Miller, J
   Buck, J
   Scott-Samuel, NE
   Roberts, NW
AF Temple, Shelby E.
   McGregor, Juliette E.
   Miles, Camilla
   Graham, Laura
   Miller, Josie
   Buck, Jordan
   Scott-Samuel, Nicholas E.
   Roberts, Nicholas W.
TI Perceiving polarization with the naked eye: characterization of human
   polarization sensitivity
SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Article
DE retina; Viking navigation; Henle fibre layer; carotenoid; zeaxanthin;
   lutein
ID PIGMENT OPTICAL-DENSITY; SCANNING LASER POLARIMETRY; MACULAR PIGMENT;
   HAIDINGERS BRUSHES; CORNEAL POLARIZATION; E-VECTOR; LINEAR
   BIREFRINGENCE; SPATIAL-DISTRIBUTION; VIKING NAVIGATION; IN-VITRO
AB Like many animals, humans are sensitive to the polarization of light. We can detect the angle of polarization using an entopticphenomenon called Haidinger's brushes, which is mediated by dichroic carotenoids in the macula lutea. While previous studies have characterized the spectral sensitivity of Haidinger's brushes, other aspects remain unexplored. We developed a novel methodology for presenting gratings in polarization-only contrast at varying degrees of polarization in order to measure the lower limits of human polarized light detection. Participants were, on average, able to perform the task down to a threshold of 56%, with some able to go as low as 23%. This makes humans the most sensitive vertebrate tested to date. Additionally, we quantified a nonlinear relationship between presented and perceived polarization angle when an observer is presented with a rotatable polarized light field. This result confirms a previous theoretical prediction of how uniaxial corneal birefringence impacts the perception of Haidinger's brushes. The rotational dynamics of Haidinger's brushes were then used to calculate corneal retardance. We suggest that psychophysical experiments, based upon the perception of polarized light, are amenable to the production of affordable technologies for self-assessment and longitudinal monitoring of visual dysfunctions such as age-related macular degeneration.
C1 [Temple, Shelby E.; McGregor, Juliette E.; Miles, Camilla; Graham, Laura; Miller, Josie; Buck, Jordan; Roberts, Nicholas W.] Univ Bristol, Sch Biol Sci, Bristol BS8 1TQ, Avon, England.
   [Scott-Samuel, Nicholas E.] Univ Bristol, Sch Expt Psychol, Bristol BS8 1TQ, Avon, England.
C3 University of Bristol; University of Bristol
RP Temple, SE (通讯作者)，Univ Bristol, Sch Biol Sci, Bristol BS8 1TQ, Avon, England.
EM shelby.temple@bristol.ac.uk
RI Temple, Shelby/ABE-7207-2020
OI Temple, Shelby/0000-0001-6447-4713; Roberts,
   Nicholas/0000-0002-4540-6683; Scott-Samuel, Nicholas/0000-0002-8270-8437
FU Biotechnology and Biological Sciences Research Council, U.K.
   [BB/G022917/1]; United States Air Force Office of Scientific Research
   [FA8655-12-1-2112]; Biotechnology and Biological Sciences Research
   Council [BB/G022917/1, BB/H01635X/1] Funding Source: researchfish; BBSRC
   [BB/G022917/1, BB/H01635X/1] Funding Source: UKRI
FX This research was funded by the Biotechnology and Biological Sciences
   Research Council, U.K. (N.W.R., no. BB/G022917/1) and the United States
   Air Force Office of Scientific Research (N.W.R., no. FA8655-12-1-2112).
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NR 61
TC 29
Z9 30
U1 1
U2 27
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8452
EI 1471-2954
J9 P ROY SOC B-BIOL SCI
JI Proc. R. Soc. B-Biol. Sci.
PD JUL 22
PY 2015
VL 282
IS 1811
AR 20150338
DI 10.1098/rspb.2015.0338
PG 9
WC Biology; Ecology; Evolutionary Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences &
   Ecology; Evolutionary Biology
GA CN8ZS
UT WOS:000358735700004
PM 26136441
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Khoshnevis, M
   Sebag, J
AF Khoshnevis, Matin
   Sebag, J.
TI Pharmacologic Vitreolysis with Ocriplasmin: Rationale for Use and
   Therapeutic Potential in Vitreo-Retinal Disorders
SO BIODRUGS
LA English
DT Article
ID POSTERIOR VITREOUS DETACHMENT; ENDOGENOUS MATRIX METALLOPROTEINASE-2;
   VITREOMACULAR TRACTION; INTRAVITREAL PLASMIN; ENZYMATIC VITREOLYSIS;
   MICROPLASMIN; RABBIT; INJECTION; ABNORMALITIES; FIBRONECTIN
AB With increased knowledge about the origins and pathophysiology of vitreo-retinal disorders-and, in particular, the central role of anomalous posterior vitreous detachment in vitreo-maculopathies-a paradigm shift from surgery to pharmacotherapy is taking place with the development of pharmacologic vitreolysis. The first approved agent for pharmacologic vitreolysis therapy is ocriplasmin, a truncated form of the nonspecific serine protease plasmin. Twelve studies comprise the current ocriplasmin clinical trial program, demonstrating the efficacy and safety of a single intravitreal injection of ocriplasmin for the treatment of patients with symptomatic vitreo-macular adhesion or vitreo-macular traction, including patients with macular holes. Although post-approval implementation of ocriplamsin in clinical practice has shown success rates of up to 78 %, there have been recent case reports of acute, transient visual dysfunction. There are thus new initiatives to further refine clinical indications for case selection and to identify possible untoward effects. Although more studies are warranted, it appears that ocriplasmin offers a good alternative to surgery. The future lies in pharmacologic vitreolysis, and the future of pharmacologic vitreolysis lies in prevention. Thus, long-term studies are needed to define a role for pharmacologic vitreolysis, in particular with ocriplasmin, in the prevention of progressive diabetic retinopathy and age-related macular degeneration.
C1 [Khoshnevis, Matin; Sebag, J.] VMR Inst Vitreous Macula Retina, Huntington Beach, CA 92647 USA.
   [Khoshnevis, Matin] Univ Calif Irvine, Irvine Sch Med, Irvine, CA USA.
C3 University of California System; University of California Irvine
RP Sebag, J (通讯作者)，VMR Inst Vitreous Macula Retina, 7677 Ctr Ave,Suite 400, Huntington Beach, CA 92647 USA.
EM mkhoshne@uci.edu; jsebag@VMRinstitute.com
RI Sebag, J./AAF-3602-2020
OI Sebag, J/0000-0001-8648-5747
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NR 59
TC 7
Z9 7
U1 0
U2 6
PU ADIS INT LTD
PI NORTHCOTE
PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND
SN 1173-8804
EI 1179-190X
J9 BIODRUGS
JI Biodrugs
PD APR
PY 2015
VL 29
IS 2
BP 103
EP 112
DI 10.1007/s40259-015-0120-y
PG 10
WC Oncology; Immunology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Immunology; Pharmacology & Pharmacy
GA CI0PJ
UT WOS:000354439300003
PM 25812991
DA 2022-11-30
ER

PT J
AU Vakalis, N
   Echiadis, G
   Pervena, A
   Deligiannis, I
   Kavalarakis, E
   Giannikakis, S
   Papaefthymiou, I
AF Vakalis, N.
   Echiadis, G.
   Pervena, A.
   Deligiannis, I.
   Kavalarakis, E.
   Giannikakis, S.
   Papaefthymiou, I.
TI Intravitreal Combination of Dexamethasone Sodium Phosphate and
   Bevacizumab in The Treatment of Exudative AMD
SO SCIENTIFIC REPORTS
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; TRIPLE THERAPY;
   TRIAMCINOLONE ACETONIDE; PHOTODYNAMIC THERAPY; VISUAL IMPAIRMENT;
   UNITED-STATES; ANGIOGENESIS; MACROPHAGES; PREVALENCE
AB The purpose of this study is to investigate the efficacy and safety of intravitreal dexamethasone sodium phosphate (DSP) combined with bevacizumab for the treatment of neovascular age-related macular degeneration (AMD). In this non comparative case study, 30 eyes of 27 patients with CNV due to AMD received intravitreal DSP (0.2 mg) and bevacizumab (1.25 mg) during a 6-month PRN (pro re nata) dosing regimen. Visual acuity, macular thickness and intraocular pressure (IOP) were monitored and recorded. After 6 months, mean retinal thickness decreased from 423.5 +/- 75.3 to 228.2 +/- 34.5 and mean visual acuity improved from 0.9 +/- 0.39 logMAR to 0.53 +/- 0.34 (p = 0.001) logMAR. During the trial period, 81 intravitreal injections were performed in 30 eyes, thus the mean number of injections per eye was 2.7 +/- 1.1. 86.7% of the eyes required 3 or less injections while only 13.3% needed 4 or more injections. None of the patients, phakic or pseudophakic, manifested an elevation of IOP during the treatment, ranging between 12 and 22 mmHg. Combined DSP and bevacizumab offers encouraging results in the challenge of AMD treatment, providing immediate response of macular edema, reduced number of intravitreal injections and stabilization or improvement of visual acuity.
C1 [Vakalis, N.; Echiadis, G.; Pervena, A.; Deligiannis, I.; Kavalarakis, E.; Giannikakis, S.; Papaefthymiou, I.] Naval Hosp Athens, Dept Ophthalmol, Ophthalmol, Athens, Greece.
RP Vakalis, N (通讯作者)，Naval Hosp Athens, Dept Ophthalmol, Ophthalmol, Athens, Greece.
EM nickvakalis@gmail.com
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NR 42
TC 10
Z9 10
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 FEB 27
PY 2015
VL 5
AR 08627
DI 10.1038/srep08627
PG 6
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA CC4BB
UT WOS:000350294500001
PM 25720826
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Yang, IH
   Wong, JH
   Chang, CM
   Chen, BK
   Tsai, YT
   Chen, WC
   Wang, ET
   Hsu, WL
   Chang, WC
AF Yang, I-Hui
   Wong, Jhen-Hong
   Chang, Che-Mai
   Chen, Ben-Kuen
   Tsai, Yao-Ting
   Chen, Wei-Chiao
   Wang, Eric Terry
   Hsu, Wen-Li
   Chang, Wei-Chiao
TI Involvement of Intracellular Calcium Mobilization in IL-8 Activation in
   Human Retinal Pigment Epithelial Cells
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE calcium; IL-8; retinal pigment epithelium
ID INTERLEUKIN-8 GENE-EXPRESSION; PHOTORECEPTOR OUTER SEGMENTS;
   NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; MACULAR DEGENERATION; OXIDATIVE
   STRESS; VITREOUS FLUID; PATHOGENESIS; INDUCTION; PATHWAY
AB PURPOSE. Calcium signaling is an important intracellular pathway. Increased intracellular calcium is associated with cytokine regulation and inflammatory signals secretion. The purpose of this study is to understand the molecular mechanisms by which calcium signaling controls IL-8 activation in human RPE cells.
   METHODS. Fluorescence-based calcium imaging and different mutants of IL-8 plasmids were used in this study. The IL-8 promoter activation, gene expression, and secretion were detected by using luciferase reporter assay, quantitative real-time PCR (Q-PCR), and ELISA, respectively. In addition, pharmacological inhibitors and small interfering RNA (siRNA) were applied to clarify the mechanisms of IL-8 activation.
   RESULTS. Our study reported that intracellular calcium mobilization activated IL-8 gene expression and secretion. Application of pharmacological inhibitor BAY 11-7082, siRNA, and plasmids of the nuclear factor j light chain enhancer of activated B cells (NF-jB) binding site, we identified that NF-kappa B is the main transcription factor involved in intracellular calcium mobilization-mediated IL-8 activation in human RPE cells.
   CONCLUSIONS. Collectively, our findings highlight the important role of intracellular calcium mobilization in the activation of IL-8. These findings may be helpful for the clinical applications in the age-related macular degeneration (AMD) prevention and treatment.
C1 [Yang, I-Hui] Kaohsiung Chang Gung Mem Hosp, Dept Ophthalmol, Kaohsiung, Taiwan.
   [Yang, I-Hui] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan.
   [Wong, Jhen-Hong; Chang, Che-Mai; Tsai, Yao-Ting; Chen, Wei-Chiao; Chang, Wei-Chiao] Taipei Med Univ, Sch Pharm, Dept Clin Pharm, Taipei 110, Taiwan.
   [Wong, Jhen-Hong; Tsai, Yao-Ting; Hsu, Wen-Li; Chang, Wei-Chiao] Kaohsiung Med Univ, Coll Med, Dept Med Genet, Kaohsiung, Taiwan.
   [Chang, Che-Mai; Wang, Eric Terry; Chang, Wei-Chiao] Taipei Med Univ, Sch Pharm, Master Program Clin Pharmacogen & Pharmacoprote, Taipei, Taiwan.
   [Chen, Ben-Kuen] Natl Cheng Kung Univ, Coll Biosci & Biotechnol, Inst Bioinformat & Biosignal Transduct, Tainan 70101, Taiwan.
   [Chang, Wei-Chiao] Taipei Med Univ, Wan Fang Hosp, Dept Pharm, Taipei 110, Taiwan.
   [Chang, Wei-Chiao] Taipei Med Univ, Ctr Comprehens Canc, Taipei 110, Taiwan.
C3 Chang Gung Memorial Hospital; Chang Gung University; Taipei Medical
   University; Kaohsiung Medical University; Taipei Medical University;
   National Cheng Kung University; Taipei Medical University; Taipei
   Municipal WanFang Hospital; Taipei Medical University
RP Chang, WC (通讯作者)，Taipei Med Univ, Sch Pharm, Dept Clin Pharm, Taipei 110, Taiwan.
EM wcc@tmu.edu.tw
OI Chang, Che-Mai/0000-0002-0353-9744; Chang, Wei-Chiao/0000-0002-8573-5924
FU welfare surcharge of tobacco products [MOHW103-TD-B-111-01]; National
   Science Council, Taiwan [NSC101-2628-B038-001-MY2,
   NSC101-2320-B038-029-MY3]
FX Supported by funding from welfare surcharge of tobacco products
   (MOHW103-TD-B-111-01) and grants from the National Science Council,
   Taiwan (NSC101-2628-B038-001-MY2 and NSC101-2320-B038-029-MY3).
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PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
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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 2015
VL 56
IS 2
BP 761
EP 769
DI 10.1167/iovs.14-15299
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CE9BC
UT WOS:000352137300009
PM 25593029
DA 2022-11-30
ER

PT J
AU Prokosch, V
   Stupp, T
   Spaniol, K
   Pham, E
   Nikol, S
AF Prokosch, Verena
   Stupp, Tobias
   Spaniol, Kristina
   Pham, Emmanuel
   Nikol, Sigrid
TI Angiogenic gene therapy does not cause retinal pathology
SO JOURNAL OF GENE MEDICINE
LA English
DT Article
DE angiogenic gene therapy; nonviral fibroblast factor 1; diabetic
   retinopathy; age-related macular degeneration
ID ENDOTHELIAL GROWTH-FACTOR; CRITICAL LIMB ISCHEMIA; DOUBLE-BLIND;
   DIABETES-MELLITUS; TRANSFER PROMOTES; CONTROLLED-TRIAL; PLACEBO;
   PLASMID; SAFETY; DISEASE
AB BackgroundThe potential negative influence of angiogenic gene therapy on the development or progression of retinal pathologies such as diabetic retinopathy (DR) or age-related macular degeneration (AMD) has led to the systematic exclusion of affected patients from trials. We investigated the role of nonviral fibroblast factor 1 (NV1FGF) in two phase II, multinational, double-blind, randomized, placebo-controlled, gene therapy trials (TALISMAN 201 and 211).
   MethodsOne hundred and fifty-two subjects with critical limb ischemia or claudication were randomized to receive eight intramuscular injections of 2.5ml of NV1FGF at 0.2mg/ml or 0.4mg/dl or placebo. One hundred and fifty-two patients received a plasmid dose of NV1FGF of up to 32mg or placebo. All patients underwent a systematic ophthalmologic examination at baseline and at 3, 6 or 12months following gene therapy. Twenty-six of these patients (Munster subgroup) received a retinal fluorescence angiography at baseline and at final examination.
   ResultsAmong those 26 patients, four of nine patients with diabetes suffered from nonproliferative DR. Three patients showed non-exsudative AMD. No change of retinal morphology or function was observed in Munster subgroup of both TALISMAN trials independent of the intramuscular NV1FGF dosage applied.
   ConclusionsAngiogenic gene therapy using NV1FGF is safe even in diabetics. Copyright (c) 2014 John Wiley & Sons, Ltd.
C1 [Prokosch, Verena; Stupp, Tobias] Univ Eye Hosp Munster, D-48149 Munster, Germany.
   [Spaniol, Kristina] Univ Eye Hosp Duesseldorf, Dusseldorf, Germany.
   [Pham, Emmanuel] Sanofi Aventis, Paris, France.
   [Nikol, Sigrid] Univ Hosp, Dept Cardiol & Angiol, Munster, Germany.
   [Nikol, Sigrid] Asklepios Clin St Georg, Dept Clin & Intervent Angiol, Hamburg, Germany.
C3 University of Munster; Sanofi-Aventis; University of Munster; Asklepios
   Klinik St. Georg
RP Prokosch, V (通讯作者)，Univ Eye Hosp Munster, Domagkstr 15, D-48149 Munster, Germany.
EM verena.prokoschwilling@ukmuenster.de
FU Medical Faculty of the University Clinic of Munster
FX This work was supported by the Medical Faculty of the University Clinic
   of Munster. No competing financial interests exist.
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NR 45
TC 1
Z9 1
U1 0
U2 2
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1099-498X
EI 1521-2254
J9 J GENE MED
JI J. Gene. Med.
PD SEP-OCT
PY 2014
VL 16
IS 9-10
BP 309
EP 316
DI 10.1002/jgm.2806
PG 8
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 AS6MU
UT WOS:000344378400004
PM 25322754
DA 2022-11-30
ER

PT J
AU Bertolotto, M
   Borgia, L
   Iester, M
AF Bertolotto, Marina
   Borgia, Luigi
   Iester, Michele
TI Hyperautofluorescence in Outer Retinal Layers Thinning
SO BIOMED RESEARCH INTERNATIONAL
LA English
DT Article
ID PIGMENT EPITHELIAL LIPOFUSCIN; OPTICAL COHERENCE TOMOGRAPHY; LAMELLAR
   MACULAR HOLES; FUNDUS AUTOFLUORESCENCE; FLUORESCENCE; ACCUMULATION;
   PSEUDOHOLES; DIAGNOSIS
AB Purpose. To evaluate if paracentral hyperautofluorescence (HAF) retinal regions, which can be occasionally found and analyzed by optical coherence tomography (OCT), were related to retinal layer changes and to detect which layer was involved. Methods. This is a cross-sectional and retrospective study. 648 OCT files were revised. OCTs that showed a paracentral HAF area by using the fundus autofluorescence imaging inHeidelberg Spectralis (Heidelberg Engineering, Germany) were selected. Then retinal layer morphology was analyzed observing OCT scans and a retinal thickness was measured. Results. 31 patients were selected: 20 patients had chronic serous epitheliopathy (CSE), 8 patients had resolved central serous chorioretinopathy (CSC), and 3 patients wet age related macular degeneration (ARMD). The HAF zones corresponded to areas of thickness reduction of the external hyporeflective band. In all these areas the retinal pigment epithelium was not atrophic and the neuroepithelium was more or less dystrophic. In particular the retinal thickness was 264 um, 232 um, and 243 um in wet ARMD, CSE, and CSC, respectively; the reduction was significant (P < 0.01) compared to the same area of the other eye. Discussion. The presence of HAF imaging might be mostly due to a "window effect" rather than an accumulation of lipofuscin.
C1 [Bertolotto, Marina; Borgia, Luigi] Is PreOftalm, I-16129 Genoa, Italy.
   [Iester, Michele] Univ Genoa, DINOGMI, Eye Clin, Anat Clin Lab Funct Diag & Treatment Glaucoma & N, I-16132 Genoa, Italy.
C3 University of Genoa
RP Iester, M (通讯作者)，Univ Genoa, DINOGMI, Eye Clin, Anat Clin Lab Funct Diag & Treatment Glaucoma & N, Viale Benedetto XV 5, I-16132 Genoa, Italy.
EM iester@unige.it
OI Iester, Michele/0000-0002-0524-2637
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NR 23
TC 4
Z9 4
U1 0
U2 4
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 2314-6133
EI 2314-6141
J9 BIOMED RES INT
JI Biomed Res. Int.
PY 2014
VL 2014
AR 741538
DI 10.1155/2014/741538
PG 6
WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Research & Experimental Medicine
GA AU7LC
UT WOS:000345781100001
PM 25276816
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Rubin, GS
AF Rubin, Gary S.
TI Measuring reading performance
SO VISION RESEARCH
LA English
DT Article
DE Reading; Low vision; Visual impairment; Outcome measures; Clinical
   trials
ID VISUAL FUNCTION; MACULAR DEGENERATION; PSYCHOPHYSICS; SPEED;
   COMPREHENSION; VARIABILITY; CONTEXT; MNREAD; ACUITY; TEXTS
AB Despite significant changes in the treatment of common eye conditions like cataract and age-related macular degeneration, reading difficulty remains the most common complaint of patients referred for low vision services. Clinical reading tests have been widely used since Jaeger introduced his test types in 1854. A brief review of the major developments in clinical reading tests is provided, followed by a discussion of some of the main controversies in clinical reading assessment. Data for the Salisbury Eye Evaluation (SEE) study demonstrate that standardised clinical reading tests are highly predictive of reading performance under natural, real world conditions, and that discrepancies between self-reported reading ability and measured reading performance may be indicative of people who are at a pre-clinical stage of disability, but are at risk for progression to clinical disability.
   If measured reading performance is to continue to increase in importance as a clinical outcome measure, there must be agreement on what should be measured (e.g. speed or comprehension) and how it should be measured (e.g. reading silently or aloud). Perhaps most important, the methods for assessing reading performance and the algorithms for scoring reading tests need to be optimised so that the reliability and responsiveness of reading tests can be improved. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Rubin, Gary S.] UCL Inst Ophthalmol, London EC1V 9EL, England.
   [Rubin, Gary S.] NIHR Moorfields Biomed Res Ctr, London, England.
C3 University of London; University College London
RP Rubin, GS (通讯作者)，UCL Inst Ophthalmol, Dept Visual Neurosci, London EC1V 9EL, England.
EM g.rubin@ucl.ac.uk
FU National Institute for Health Research (NIHR) Biomedical Research Centre
   based at Moorfields Eye Hospital NHS Foundation Trust; UCL Institute of
   Ophthalmology; Fight for Sight [1777/78] Funding Source: researchfish
FX The writing of this manuscript 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.
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NR 51
TC 88
Z9 91
U1 0
U2 45
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0042-6989
EI 1878-5646
J9 VISION RES
JI Vision Res.
PD SEP 20
PY 2013
VL 90
SI SI
BP 43
EP 51
DI 10.1016/j.visres.2013.02.015
PG 9
WC Neurosciences; Ophthalmology; Psychology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Ophthalmology; Psychology
GA 205SF
UT WOS:000323464400008
PM 23506967
OA Bronze
DA 2022-11-30
ER

PT J
AU Rivera, CG
   Bader, JS
   Popel, AS
AF Rivera, Corban G.
   Bader, Joel S.
   Popel, Aleksander S.
TI Angiogenesis-Associated Crosstalk Between Collagens, CXC Chemokines, and
   Thrombospondin Domain-Containing Proteins
SO ANNALS OF BIOMEDICAL ENGINEERING
LA English
DT Article
DE CXC chemokine; Type IV collagen; Thrombospondin-1; Angiogenesis;
   Crosstalk; Interactome; Syndecan
ID IN-VIVO; ENRICHMENT ANALYSIS; TUMOR ANGIOGENESIS; ENDOTHELIAL-CELLS; IV
   COLLAGEN; PEPTIDES; NETWORK; NEOVASCULARIZATION; PROLIFERATION;
   MIGRATION
AB Excessive vascularization is a hallmark of many diseases including cancer, rheumatoid arthritis, diabetic nephropathy, pathologic obesity, age-related macular degeneration, and asthma. Compounds that inhibit angiogenesis represent potential therapeutics for many diseases. Karagiannis and Popel [Proc. Natl. Acad. Sci. USA 105(37):13775-13780, 2008] used a bioinformatics approach to identify more than 100 peptides with sequence homology to known angiogenesis inhibitors. The peptides could be grouped into families by the conserved domain of the proteins they were derived from. The families included type IV collagen fibrils, CXC chemokine ligands, and type I thrombospondin domain-containing proteins. The relationships between these families have received relatively little attention. To investigate these relationships, we approached the problem by placing the families of proteins in the context of the human interactome including > 120,000 physical interactions among proteins, genes, and transcripts. We built on a graph theoretic approach to identify proteins that may represent conduits of crosstalk between protein families. We validated these findings by statistical analysis and analysis of a time series gene expression data set taken during angiogenesis. We identified six proteins at the center of the angiogenesis-associated network including three syndecans, MMP9, CD44, and versican. These findings shed light on the complex signaling networks that govern angiogenesis phenomena.
C1 [Rivera, Corban G.; Bader, Joel S.; Popel, Aleksander S.] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA.
C3 Johns Hopkins University
RP Rivera, CG (通讯作者)，Johns Hopkins Univ, Sch Med, Dept Biomed Engn, 720 Rutland Ave,613 Traylor Bldg, Baltimore, MD 21205 USA.
EM cgrivera@jhu.edu
RI Bader, Joel/A-1818-2009; Popel, Aleksander S/A-6724-2009
OI Bader, Joel/0000-0002-6020-4625; Popel, Aleksander/0000-0002-6706-9235
FU NIH [R01 HL101200, R01 CA138264]; NATIONAL CANCER INSTITUTE
   [R01CA138264] Funding Source: NIH RePORTER; NATIONAL HEART, LUNG, AND
   BLOOD INSTITUTE [R33HL087351, R01HL101200] Funding Source: NIH RePORTER
FX The work was supported by NIH grants R01 HL101200 and R01 CA138264. The
   authors would like to thank Emmanouil Karagiannis for helpful
   discussions at the initial stage of the project. We would also like to
   thank Sofie Mellberg and Lena Claesson-Welsh for use of their time
   series gene expression dataset. CGR implemented the method, performed
   the analysis, generated the images and wrote the paper. ASP and JSB
   designed the study and edited the paper.
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NR 38
TC 20
Z9 20
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0090-6964
J9 ANN BIOMED ENG
JI Ann. Biomed. Eng.
PD AUG
PY 2011
VL 39
IS 8
BP 2213
EP 2222
DI 10.1007/s10439-011-0325-2
PG 10
WC Engineering, Biomedical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering
GA 785YK
UT WOS:000292268900010
PM 21590489
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Lombardi, G
   Calistri, A
   Curtarello, M
   Giudice, GL
   Piermarocchi, S
   Prosdocimo, G
   Palu, G
   Parolin, C
AF Lombardi, G.
   Calistri, A.
   Curtarello, M.
   Giudice, G. L.
   Piermarocchi, S.
   Prosdocimo, G.
   Palu, G.
   Parolin, C.
TI HIV-1-mediated delivery of a short hairpin RNA targeting vascular
   endothelial growth factor in human retinal pigment epithelium cells
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID GENE-TRANSFER; CHOROIDAL NEOVASCULARIZATION; OCULAR NEOVASCULARIZATION;
   TRANSGENE EXPRESSION; LENTIVIRAL VECTOR; MACULAR DEGENERATION; MEDIATED
   DELIVERY; HUMAN-LYMPHOCYTES; MOUSE MODEL; THERAPY
AB Background: Vascular endothelial growth factor (VEGF) has been shown to play a major role in the pathological neovascularisation that occurs in degenerative retinal diseases like age-related macular degeneration (AMD). Although several approaches to attenuate VEGF show significant promise, repeated treatments are required to achieve therapeutic benefits. As lentiviruses efficiently and stably infect resting cells, a human immunodeficiency virus type 1 (HIV-1)-based vector was used for the delivery and long-term endogenous expression of a short hairpin RNA (shRNA) specific for VEGF in postmitotic human retinal pigment epithelium (RPE) cells.
   Methods: An HIV-1 vector expressing a shRNA targeting VEGF was developed and adopted to transduce RPE cell cultures, in both normoxic and hypoxic conditions in vitro. Intracellular VEGF expression was analysed by western blotting, and the release of VEGF in culture supernatants was determined by ELISA.
   Results: At least 90% of RPE cells were successfully transduced by HIV-1 virions. Inhibition of VEGF expression and reduction by 95% of VEGF release in transduced cells were achieved. Moreover, shRNA-VEGF effectively and specifically prevented hypoxia-induced VEGF upregulation.
   Conclusion: HIV-1-mediated delivery of a shRNA-VEGF leading to gene expression knockdown could represent a novel therapeutic strategy against neovascularisation-related eye diseases.
C1 [Lombardi, G.; Calistri, A.; Curtarello, M.; Palu, G.] Univ Padua, Dept Histol Microbiol & Med Biotechnol, I-35131 Padua, Italy.
   [Giudice, G. L.] S Antonio Hosp, Dept Ophthalmol, Padua, Italy.
   [Piermarocchi, S.] Univ Padua, Dept Neurosci, I-35131 Padua, Italy.
   [Prosdocimo, G.] Conegliano Hosp, Dept Ophthalmol, Treviso, Italy.
   [Parolin, C.] Univ Padua, Dept Biol, I-35131 Padua, Italy.
C3 University of Padua; ULSS 6 Euganea; Ospedale Sant'antonio Padova;
   University of Padua; ULSS 2 Marca TV; Ospedale Conegliano; University of
   Padua
RP Parolin, C (通讯作者)，Univ Padua, Dept Biol, Viale G Colombo 3, I-35131 Padua, Italy.
EM cristina.parolin@unipd.it
RI Curtarello, Matteo/K-4021-2016; Curtarello, Matteo/P-8120-2019; LO
   GIUDICE, GIUSEPPE/GQB-0418-2022
OI Curtarello, Matteo/0000-0003-3133-4807; Curtarello,
   Matteo/0000-0003-3133-4807; LOMBARDI, GIULIA/0000-0001-6423-8358;
   Calistri, Arianna/0000-0002-6881-7936
FU Ricerca Sanitaria Finalizzata 2004; Istituto Superiore di Sanita
   [30G.24]; University of Padua
FX This work was supported by Ricerca Sanitaria Finalizzata 2004 grants
   from the Regione Veneto, by Istituto Superiore di Sanita 30G.24 and by
   Ex 60% grants from the University of Padua.
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NR 33
TC 3
Z9 3
U1 0
U2 6
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD FEB
PY 2009
VL 93
IS 2
BP 244
EP 248
DI 10.1136/bjo.2008.138388
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 399XZ
UT WOS:000262833900023
PM 19174401
DA 2022-11-30
ER

PT J
AU Holers, VM
AF Holers, V. Michael
TI The spectrum of complement alternative pathway-mediated diseases
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE complement; inhibitors; complement deficiency; genetics
ID HEMOLYTIC-UREMIC-SYNDROME; COLLAGEN-INDUCED ARTHRITIS; EXPERIMENTAL
   ALLERGIC ENCEPHALOMYELITIS; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA;
   TRANSLATIONAL MINIREVIEW SERIES; EXPERIMENTAL AUTOIMMUNE
   ENCEPHALOMYELITIS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; HUMORAL
   IMMUNE-RESPONSE; AMYLOID-P COMPONENT; SPINAL-CORD-INJURY
AB The complement system has once again come into prominence in the therapeutic development arena. The recent approval of an inhibitory monoclonal antibody, eculizumab, which is directed against complement component C5 for the disease paroxysmal nocturnal hemoglobinuria has provided the initial validation of this system as a therapeutic target. Preclinical studies using animal models and human-derived samples demonstrate that inhibition of complement ameliorates many inflammatory and autoimmune disease manifestations. Major efforts continue to define the most optimal means to block complement activation in a cost-effective manner. Because the system is initiated through three pathways and generates at least six immunoregulatory and pro-inflammatory mediators, there is substantial complexity to this problem. One pathway, designated the alternative pathway, has recently been shown to play a particularly important role in preclinical disease models. Further evidence of the importance of the alternative pathway has been provided by studies of human diseases, where mutations or dysfunctional polymorphisms that promote activation of this pathway are highly associated with the diseases atypical hemolytic uremic syndrome, dense deposit disease, and age-related macular degeneration. This article reviews evidence in support of the essential role of the alternative pathway in the generation of tissue injury and the rationale for development of therapies that modulate its activity.
C1 Univ Colorado, Denver Sch Med, Div Rheumatol, Dept Med & Immunol, Aurora, CO 80045 USA.
C3 University of Colorado System; University of Colorado Anschutz Medical
   Campus
RP Holers, VM (通讯作者)，Univ Colorado, Denver Sch Med, Div Rheumatol, Dept Med & Immunol, Mail Stop B115,POB 6511, Aurora, CO 80045 USA.
EM michael.holers@uchsc.edu
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NR 136
TC 163
Z9 224
U1 0
U2 22
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-2896
EI 1600-065X
J9 IMMUNOL REV
JI Immunol. Rev.
PD JUN
PY 2008
VL 223
BP 300
EP 316
DI 10.1111/j.1600-065X.2008.00641.x
PG 17
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA 325CG
UT WOS:000257565200019
PM 18613844
DA 2022-11-30
ER

PT J
AU Sarks, J
   Tang, K
   Killingsworth, M
   Arnold, J
   Sarks, S
AF Sarks, J
   Tang, K
   Killingsworth, M
   Arnold, J
   Sarks, S
TI Development of atrophy of the retinal pigment epithelium around
   disciform scars
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; GEOGRAPHIC ATROPHY; FUNDUS AUTOFLUORESCENCE;
   ENLARGEMENT; PREVALENCE; PATTERNS; DISEASE; EYES
AB Background/aims: Eyes with burnt out disciform scars secondary to age related macular degeneration (AMD) are regarded as visually stable. The aim of this study is to report the subsequent development of atrophy of the retinal pigment epithelium (RPE) around the scars and discuss the possible basis.
   Methods: 20 eyes from 18 patients were observed to develop atrophy around choroidal neovascularisation (CNV). A method of measuring expansion of the atrophy over time is described using the Topcon Imagenet 2000 system. An additional 10 clinicopathological examples were reviewed.
   Results: Clinically CNV became surrounded initially by a ring of pallor that progressed to an expanding band of atrophy of the RPE. It developed most rapidly in the first 3 years after CNV became quiescent but then continued to expand slowly to more than three times the size of the scar. Histopathological specimens showed large choroidal vessels entering the scars directly and a reduced number of small choroidal vessels beneath and around the scar
   Conclusions: Disciform scars may become surrounded by an expanding band of atrophy of the RPE, postulated to result from remodelling of the choroidal circulation. The ongoing enlargement of the resulting scotoma may need to be considered when planning management and assessing treatment outcomes.
C1 Prince Wales Med Res Inst, Sydney, NSW, Australia.
C3 Prince Wales Medical Research Institute
RP Sarks, S (通讯作者)，Prince Wales Med Res Inst, Sydney, NSW, Australia.
EM jssarks@bigpond.net.au
RI Killingsworth, Murray C/G-5908-2015; Killingsworth, Murray/O-3736-2019
OI Killingsworth, Murray/0000-0002-6125-1183
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NR 22
TC 29
Z9 29
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 APR
PY 2006
VL 90
IS 4
BP 442
EP 446
DI 10.1136/bjo.2005.083022
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 023CH
UT WOS:000236102400018
PM 16547324
OA Green Published
DA 2022-11-30
ER

PT J
AU Wiszniewski, W
   Zaremba, CM
   Yatsenko, AN
   Jamrich, M
   Wensel, TG
   Lewis, RA
   Lupski, JR
AF Wiszniewski, W
   Zaremba, CM
   Yatsenko, AN
   Jamrich, M
   Wensel, TG
   Lewis, RA
   Lupski, JR
TI ABCA4 mutations causing mislocalization are found frequently in patients
   with severe retinal dystrophies
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID CONE-ROD DYSTROPHY; DISEASE GENE ABCR; RECESSIVE RETINITIS-PIGMENTOSA;
   CASSETTE TRANSPORTER GENE; STARGARDT-DISEASE; MACULAR DEGENERATION;
   FUNCTIONAL-ANALYSIS; XENOPUS-LAEVIS; RIM PROTEIN; FAMILY
AB ABCA4, also called ABCR, is a retinal-specific member of the ATP-binding cassette (ABC) family that functions in photoreceptor outer segments as a flipase of all-trans retinal. Homozygous and compound heterozygous ABCA4 mutations are associated with various autosomal recessive retinal dystrophies, whereas heterozygous ABCA4 mutations have been associated with dominant susceptibility to age-related macular degeneration in both humans and mice. We analyzed a cohort of 29 arRP families for the mutations in ABCA4 with a commercial microarray, ABCR-400 in addition to direct sequencing and segregation analysis, and identified both mutant alleles in two families (7%): compound heterozygosity for missense (R602W) and nonsense (R408X) alleles and homozygosity for a complex [L541P; A1038V] allele. The missense mutations were analyzed functionally in the photoreceptors of Xenopus laevis tadpoles, which revealed mislocalization of ABCA4 protein. These mutations cause retention of ABCA4 in the photoreceptor inner segment, likely by impairing correct folding, resulting in the total absence of physiologic protein function. Patients with different retinal dystrophies harboring two misfolding alleles exhibit early age-of-onset (AO) (5-12 years) of retinal disease. Our data suggest that a class of ABCA4 mutants may be an important determinant of the AO of disease.
C1 Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   Baylor Coll Med, Dept Biochem, Houston, TX 77030 USA.
   Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
   Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
   Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA.
   Texas Childrens Hosp, Houston, TX 77030 USA.
C3 Baylor College of Medicine; Baylor College of Medicine; Baylor College
   of Medicine; Baylor College of Medicine; Baylor College of Medicine;
   Baylor College of Medicine
RP Lupski, JR (通讯作者)，Baylor Coll Med, Dept Mol & Human Genet, Room 604B,1 Baylor Plaza, Houston, TX 77030 USA.
EM jlupski@bcm.tmc.edu
OI Yatsenko, Alexander/0000-0002-1690-0172; Wensel,
   Theodore/0000-0003-3518-9352
FU NEI NIH HHS [EY13255] Funding Source: Medline; NATIONAL EYE INSTITUTE
   [R01EY013255] Funding Source: NIH RePORTER
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NR 48
TC 70
Z9 74
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD OCT 1
PY 2005
VL 14
IS 19
BP 2769
EP 2778
DI 10.1093/hmg/ddi310
PG 10
WC Biochemistry & Molecular Biology; Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 965AV
UT WOS:000231923000001
PM 16103129
OA Bronze
DA 2022-11-30
ER

PT J
AU Grisanti, S
   Canbek, S
   Kaiserling, E
   Adam, A
   Lafaut, B
   Gelisken, F
   Szurman, P
   Henke-Fahle, S
   Oficjalska-Mlynczak, J
   Bartz-Schmidt, KU
AF Grisanti, S
   Canbek, S
   Kaiserling, E
   Adam, A
   Lafaut, B
   Gelisken, F
   Szurman, P
   Henke-Fahle, S
   Oficjalska-Mlynczak, J
   Bartz-Schmidt, KU
TI Expression of endoglin in choroidal neovascularization
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE endoglin; endothelial cells; choroidal neovascular membranes;
   age-related macular degeneration; cellular proliferation
ID MACULAR DEGENERATION; MEMBRANES; RECEPTOR
AB Endoglin (CD105) is a membrane protein involved in the TGF-beta receptor signalling pathway with predominant expression by proliferating endothelial cells. The aim of this study is to analyze the expression of Endoglin in choroidal neovascularization membranes (CNVM) and to compare it to the overall proliferative status of CNVM.
   Thirty surgically excised CNVM, secondary to age-related macular degeneration, were investigated using light microscopic immunohistochemistry and confocal immunofluorescence microscopy using verified antibodies directed against the endothelial cell markers Endoglin, von Willebrand factor (vWF) and CD34 and the proliferation marker Ki-67. Donor eyes were used as controls.
   A selective expression of CD34 and vWF as well as Endoglin was found in endothelial cells. Endoglin expression was elevated in vascular endothelial cells contained within CNVM, but a moderate Endoglin expression could also be visualized in quiescent CD34 and vWF positive ocular vasculature. Ki-67 positive cells were detected in CNVM, but these were rarely endothelial cells.
   Endoglin expression in endothelial cells of CNVM is increased, but rarely associated with a concomitant expression of the proliferation marker Ki-67. The elevated expression of Endoglin in surgically excised CNVM suggests a persisting post-mitotic activation in an advanced stage of this neovascular tissue. (C) 2003 Elsevier Ltd. All rights reserved.
C1 Univ Tubingen, Ctr Ophthalmol, Dept Vitreoretinal Surg, D-72070 Tubingen, Germany.
   Univ Tubingen, Inst Pathol, D-72070 Teubingen, Germany.
   State Univ Ghent, Brugge, Belgium.
   Univ Wroclaw, Dept Ophthalmol, PL-50138 Wroclaw, Poland.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University
   Hospital; Eberhard Karls University of Tubingen; Ghent University;
   University of Wroclaw
RP Grisanti, S (通讯作者)，Univ Tubingen, Ctr Ophthalmol, Dept Vitreoretinal Surg, Schleichstr 12-15, D-72070 Tubingen, Germany.
EM salvatore.grisanti@uni-tuebingen.de
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NR 16
TC 18
Z9 19
U1 0
U2 1
PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
J9 EXP EYE RES
JI Exp. Eye Res.
PD FEB
PY 2004
VL 78
IS 2
BP 207
EP 213
DI 10.1016/j.exer.2003.11.008
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 773TQ
UT WOS:000188939200005
PM 14729353
DA 2022-11-30
ER

PT J
AU Hassel, C
   Couchet, M
   Jacquemot, N
   Blavignac, C
   Loi, C
   Moinard, C
   Cia, D
AF Hassel, Chervin
   Couchet, Morgane
   Jacquemot, Nathalie
   Blavignac, Christelle
   Loi, Cecile
   Moinard, Christophe
   Cia, David
TI Citrulline protects human retinal pigment epithelium from hydrogen
   peroxide and iron/ascorbate induced damages
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Article
DE ARPE-19 (human RPE cell line); citrulline; hydrogen peroxide; iron;
   ascorbate; oxidative stress
ID BILOBA EXTRACT EGB-761; ORAL L-CITRULLINE; OXIDATIVE STRESS;
   LIPID-PEROXIDATION; IRON ACCUMULATION; CELLS; SUPPLEMENTATION; HYDROXYL;
   ARGININE; RPE
AB Oxidative stress plays an important role in the ageing of the retina and in the pathogenesis of retinal diseases such as age-related macular degeneration (ARMD). Hydrogen peroxide is a reactive oxygen species generated by the photo-excited lipofuscin that accumulates during ageing in the retinal pigment epithelium (RPE), and the age-related accumulation of lipofuscin is associated with ARMD. Iron also accumulates with age in the RPE that may contribute to ARMD as an important source of oxidative stress. The aim of this work was to investigate the effects of L-Citrulline (CIT), a naturally occurring amino acid with known antioxidant properties, on oxidative stressed cultured RPE cells. Human RPE (ARPE-19) cells were exposed to hydrogen peroxide (H2O2) or iron/ascorbate (I/A) for 4 h, either in the presence of CIT or after 24 h of pretreatment. Here, we show that supplementation with CIT protects ARPE-19 cells against H2O2 and I/A. CIT improves cell metabolic activity, decreases ROS production, limits lipid peroxidation, reduces cell death and attenuates IL-8 secretion. Our study evidences that CIT is able to protect human RPE cells from oxidative damage and suggests potential protective effect for the treatment of retinal diseases associated with oxidative stress.
C1 [Hassel, Chervin; Jacquemot, Nathalie; Cia, David] Univ Clermont Auvergne, Lab Biophys Neurosensorielle, INSERM, U1107,NEURO DOL, Clermont Ferrand, France.
   [Couchet, Morgane; Moinard, Christophe] Univ Grenoble Alpes, Lab Bioenerget Fondamentale & Appl, INSERM, U1055, Grenoble, France.
   [Blavignac, Christelle] Univ Clermont Auvergne, Ctr Imagerie Cellulaire Sante, Clermont Ferrand, France.
   [Loi, Cecile] CITRAGE, Boissy St Leger, France.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm);
   Universite Clermont Auvergne (UCA); Institut National de la Sante et de
   la Recherche Medicale (Inserm); UDICE-French Research Universities;
   Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA);
   Universite Clermont Auvergne (UCA)
RP Cia, D (通讯作者)，UMR Inserm 1107, Lab Biophys Neurosensorielle, 28 Pl Henri Dunant,BP 38, F-63001 Clermont Ferrand, France.
EM david.cia@uca.fr
RI Hassel, Chervin/GQP-5329-2022
OI Cia, David/0000-0002-1146-7904
FU Citrage
FX Citrage
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NR 55
TC 0
Z9 0
U1 1
U2 3
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 MAY
PY 2022
VL 26
IS 10
BP 2808
EP 2818
DI 10.1111/jcmm.17294
EA APR 2022
PG 11
WC Cell Biology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine
GA 1D7TM
UT WOS:000785907500001
PM 35460170
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Rozanowska, MB
   Rozanowski, B
AF Rozanowska, Malgorzata B.
   Rozanowski, Bartosz
TI Photodegradation of Lipofuscin in Suspension and in ARPE-19 Cells and
   the Similarity of Fluorescence of the Photodegradation Product with
   Oxidized Docosahexaenoate
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE lipofuscin; retina; retinal pigment epithelium; docosahexaenoate;
   docosahexaenoic acid; fluorescence; photodegradation; photobleaching;
   cell viability; endocytic activity
ID RETINAL-PIGMENT EPITHELIUM; QUANTITATIVE FUNDUS AUTOFLUORESCENCE;
   AGE-RELATED-CHANGES; RETINYLIDENE-N-RETINYLETHANOLAMINE;
   LIPID-PEROXIDATION PRODUCTS; PHAGOCYTIC-ACTIVITY; HUMAN RPE; MACULAR
   DEGENERATION; SPATIAL-DISTRIBUTION; A2E
AB Retinal lipofuscin accumulates with age in the retinal pigment epithelium (RPE), where its fluorescence properties are used to assess retinal health. It was observed that there is a decrease in lipofuscin fluorescence above the age of 75 years and in the early stages of age-related macular degeneration (AMD). The purpose of this study was to investigate the response of lipofuscin isolated from human RPE and lipofuscin-laden cells to visible light, and to determine whether an abundant component of lipofuscin, docosahexaenoate (DHA), can contribute to lipofuscin fluorescence upon oxidation. Exposure of lipofuscin to visible light leads to a decrease in its long-wavelength fluorescence at about 610 nm, with a concomitant increase in the short-wavelength fluorescence. The emission spectrum of photodegraded lipofuscin exhibits similarity with that of oxidized DHA. Exposure of lipofuscin-laden cells to light leads to a loss of lipofuscin granules from cells, while retaining cell viability. The spectral changes in fluorescence in lipofuscin-laden cells resemble those seen during photodegradation of isolated lipofuscin. Our results demonstrate that fluorescence emission spectra, together with quantitation of the intensity of long-wavelength fluorescence, can serve as a marker useful for lipofuscin quantification and for monitoring its oxidation, and hence useful for screening the retina for increased oxidative damage and early AMD-related changes.
C1 [Rozanowska, Malgorzata B.] Cardiff Univ, Sch Optometry & Vis Sci, Cardiff CF24 4HQ, Wales.
   [Rozanowska, Malgorzata B.] Cardiff Univ, Cardiff Inst Tissue Engn & Repair CITER, Cardiff CF10 3NB, Wales.
   [Rozanowski, Bartosz] Pedag Univ Krakow, Inst Biol, PL-30084 Krakow, Poland.
C3 Cardiff University; Cardiff University; Pedagogical University of Cracow
RP Rozanowska, MB (通讯作者)，Cardiff Univ, Sch Optometry & Vis Sci, Cardiff CF24 4HQ, Wales.; Rozanowska, MB (通讯作者)，Cardiff Univ, Cardiff Inst Tissue Engn & Repair CITER, Cardiff CF10 3NB, Wales.
EM RozanowskaMB@cardiff.ac.uk; Bartosz.Rozanowski@up.krakow.pl
RI ; Rozanowska, Malgorzata/B-7860-2014
OI Rozanowski, Bartosz/0000-0002-6362-1758; Rozanowska,
   Malgorzata/0000-0003-2913-8954
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NR 106
TC 2
Z9 2
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 JAN
PY 2022
VL 23
IS 2
AR 922
DI 10.3390/ijms23020922
PG 23
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA YO0BI
UT WOS:000747613500001
PM 35055111
OA Green Accepted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Tan, TE
   Fenner, BJ
   Barathi, VA
   Tun, SBB
   Wey, YS
   Tsai, ASH
   Su, XY
   Lee, SY
   Cheung, CMG
   Wong, TY
   Mehta, JS
   Teo, KYC
AF Tan, Tien-En
   Fenner, Beau James
   Barathi, Veluchamy Amutha
   Tun, Sai Bo Bo
   Wey, Yeo Sia
   Tsai, Andrew Shih Hsiang
   Su, Xinyi
   Lee, Shu Yen
   Cheung, Chui Ming Gemmy
   Wong, Tien Yin
   Mehta, Jodhbir Singh
   Teo, Kelvin Yi Chong
TI Gene-Based Therapeutics for Acquired Retinal Disease: Opportunities and
   Progress
SO FRONTIERS IN GENETICS
LA English
DT Review
DE gene therapy; genome editing; ocular biofactory; neovascular age related
   macular degeneration (nAMD); geographic atrophy (GA); diabetic
   retinopathy (DR); diabetic macular edema (DME); retinal vascular disease
ID PROLIFERATIVE DIABETIC-RETINOPATHY; INTERNAL LIMITING MEMBRANE;
   ANTI-VEGF TREATMENT; MACULAR DEGENERATION; PANRETINAL PHOTOCOAGULATION;
   CHOROIDAL NEOVASCULARIZATION; INTRAVITREOUS RANIBIZUMAB; GEOGRAPHIC
   ATROPHY; SECONDARY-ANALYSIS; GLOBAL PREVALENCE
AB Acquired retinal diseases such as age-related macular degeneration and diabetic retinopathy rank among the leading causes of blindness and visual loss worldwide. Effective treatments for these conditions are available, but often have a high treatment burden, and poor compliance can lead to disappointing real-world outcomes. Development of new treatment strategies that provide more durable treatment effects could help to address some of these unmet needs. Gene-based therapeutics, pioneered for the treatment of monogenic inherited retinal disease, are being actively investigated as new treatments for acquired retinal disease. There are significant advantages to the application of gene-based therapeutics in acquired retinal disease, including the presence of established therapeutic targets and common pathophysiologic pathways between diseases, the lack of genotype-specificity required, and the larger potential treatment population per therapy. Different gene-based therapeutic strategies have been attempted, including gene augmentation therapy to induce in vivo expression of therapeutic molecules, and gene editing to knock down genes encoding specific mediators in disease pathways. We highlight the opportunities and unmet clinical needs in acquired retinal disease, review the progress made thus far with current therapeutic strategies and surgical delivery techniques, and discuss limitations and future directions in the field.
C1 [Tan, Tien-En; Fenner, Beau James; Tsai, Andrew Shih Hsiang; Lee, Shu Yen; Cheung, Chui Ming Gemmy; Wong, Tien Yin; Mehta, Jodhbir Singh; Teo, Kelvin Yi Chong] Singapore Natl Eye Ctr, Singapore, Singapore.
   [Tan, Tien-En; Fenner, Beau James; Barathi, Veluchamy Amutha; Tun, Sai Bo Bo; Wey, Yeo Sia; Tsai, Andrew Shih Hsiang; Su, Xinyi; Lee, Shu Yen; Cheung, Chui Ming Gemmy; Wong, Tien Yin; Mehta, Jodhbir Singh; Teo, Kelvin Yi Chong] Singapore Eye Res Inst, Singapore, Singapore.
   [Tan, Tien-En; Fenner, Beau James; Barathi, Veluchamy Amutha; Tsai, Andrew Shih Hsiang; Lee, Shu Yen; Cheung, Chui Ming Gemmy; Wong, Tien Yin; Mehta, Jodhbir Singh; Teo, Kelvin Yi Chong] Duke Natl Univ Singapore, Med Sch, Singapore, Singapore.
   [Barathi, Veluchamy Amutha; Su, Xinyi] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.
   [Su, Xinyi] ASTAR, Inst Mol & Cell Biol IMCB, Singapore, Singapore.
   [Su, Xinyi] Natl Univ Singapore Hosp, Dept Ophthalmol, Singapore, Singapore.
C3 Singapore National Eye Center; National University of Singapore;
   Singapore National Eye Center; National University of Singapore;
   National University of Singapore; Agency for Science Technology &
   Research (A*STAR); A*STAR - Institute of Molecular & Cell Biology
   (IMCB); National University of Singapore
RP Teo, KYC (通讯作者)，Singapore Natl Eye Ctr, Singapore, Singapore.; Teo, KYC (通讯作者)，Singapore Eye Res Inst, Singapore, Singapore.; Teo, KYC (通讯作者)，Duke Natl Univ Singapore, Med Sch, Singapore, Singapore.
EM kelvin.teo.y.c@singhealth.com.sg
RI Tun, Sai Bo Bo/GRF-2470-2022; TUN, SAI BO BO/O-1085-2018
OI TUN, SAI BO BO/0000-0002-2013-8379; Fenner, Beau/0000-0002-5356-7604
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NR 92
TC 2
Z9 2
U1 1
U2 3
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 1664-8021
J9 FRONT GENET
JI Front. Genet.
PD DEC 7
PY 2021
VL 12
AR 795010
DI 10.3389/fgene.2021.795010
PG 11
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA YI0OJ
UT WOS:000743556600001
PM 34950193
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Gauvain, G
   Akolkar, H
   Chaffiol, A
   Arcizet, F
   Khoei, MA
   Desrosiers, M
   Jaillard, C
   Caplette, R
   Marre, O
   Bertin, S
   Fovet, CM
   Demilly, J
   Forster, V
   Brazhnikova, E
   Hantraye, P
   Pouget, P
   Douar, A
   Pruneau, D
   Chavas, J
   Sahel, JA
   Dalkara, D
   Duebel, J
   Benosman, R
   Picaud, S
AF Gauvain, Gregory
   Akolkar, Himanshu
   Chaffiol, Antoine
   Arcizet, Fabrice
   Khoei, Mina A.
   Desrosiers, Melissa
   Jaillard, Celine
   Caplette, Romain
   Marre, Olivier
   Bertin, Stephane
   Fovet, Claire-Maelle
   Demilly, Joanna
   Forster, Valerie
   Brazhnikova, Elena
   Hantraye, Philippe
   Pouget, Pierre
   Douar, Anne
   Pruneau, Didier
   Chavas, Joel
   Sahel, Jose-Alain
   Dalkara, Deniz
   Duebel, Jens
   Benosman, Ryad
   Picaud, Serge
TI Optogenetic therapy: high spatiotemporal resolution and pattern
   discrimination compatible with vision restoration in non-human primates
SO COMMUNICATIONS BIOLOGY
LA English
DT Article
ID RESTORES VISUAL RESPONSES; BIPOLAR CELLS; GENE-THERAPY; RPE65 MUTATIONS;
   GANGLION-CELLS; OCULAR SAFETY; BLIND; TRIAL; MIDGET; CHANNELRHODOPSIN-2
AB Vision restoration is an ideal medical application for optogenetics, because the eye provides direct optical access to the retina for stimulation. Optogenetic therapy could be used for diseases involving photoreceptor degeneration, such as retinitis pigmentosa or age-related macular degeneration. We describe here the selection, in non-human primates, of a specific optogenetic construct currently tested in a clinical trial. We used the microbial opsin ChrimsonR, and showed that the AAV2.7m8 vector had a higher transfection efficiency than AAV2 in retinal ganglion cells (RGCs) and that ChrimsonR fused to tdTomato (ChR-tdT) was expressed more efficiently than ChrimsonR. Light at 600 nm activated RGCs transfected with AAV2.7m8 ChR-tdT, from an irradiance of 1015 photons.cm(-2).s(-1). Vector doses of 5 x 10(10) and 5 x 10(11) vg/eye transfected up to 7000 RGCs/mm(2) in the perifovea, with no significant immune reaction. We recorded RGC responses from a stimulus duration of 1ms upwards. When using the recorded activity to decode stimulus information, we obtained an estimated visual acuity of 20/249, above the level of legal blindness (20/400). These results lay the groundwork for the ongoing clinical trial with the AAV2.7m8 - ChR-tdT vector for vision restoration in patients with retinitis pigmentosa.
C1 [Gauvain, Gregory; Akolkar, Himanshu; Chaffiol, Antoine; Arcizet, Fabrice; Khoei, Mina A.; Desrosiers, Melissa; Jaillard, Celine; Caplette, Romain; Marre, Olivier; Forster, Valerie; Brazhnikova, Elena; Sahel, Jose-Alain; Dalkara, Deniz; Duebel, Jens; Benosman, Ryad; Picaud, Serge] Sorbonne Univ, INSERM, CNRS, Inst Vis, 17 Rue Moreau, F-75012 Paris, France.
   [Akolkar, Himanshu; Sahel, Jose-Alain; Benosman, Ryad] Univ Pittsburgh, Med Ctr, Dept Ophthalmol, Pittsburgh, PA USA.
   [Bertin, Stephane; Sahel, Jose-Alain] CHNO Quinze Vingts, INSERM DGOS CIC 1423, 28 Rue Charenton, F-75012 Paris, France.
   [Fovet, Claire-Maelle; Demilly, Joanna; Hantraye, Philippe] Commissariat Energie Atom & Energies Alternat CEA, Inst Imagerie Biomed I2BM, MIRcen, Dept Sci Vivant DSV, F-92260 Fontenay Aux Roses, France.
   [Pouget, Pierre] UPMC, UMRS 1127, ICM, INSERM,CNRS,UMR 7225,U1127, Paris, France.
   [Douar, Anne; Pruneau, Didier; Chavas, Joel] Gensight Biol, 74 Rue Faubourg St Antoine, F-75012 Paris, France.
C3 Centre National de la Recherche Scientifique (CNRS); Institut National
   de la Sante et de la Recherche Medicale (Inserm); UDICE-French Research
   Universities; Sorbonne Universite; Universite Paris Cite; Pennsylvania
   Commonwealth System of Higher Education (PCSHE); University of
   Pittsburgh; CHNO des Quinze-Vingts; UDICE-French Research Universities;
   Sorbonne Universite; CEA; UDICE-French Research Universities; Universite
   Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CNRS
   - National Institute for Biology (INSB); Institut National de la Sante
   et de la Recherche Medicale (Inserm); UDICE-French Research
   Universities; Sorbonne Universite; Universite Paris Cite
RP Picaud, S (通讯作者)，Sorbonne Univ, INSERM, CNRS, Inst Vis, 17 Rue Moreau, F-75012 Paris, France.
EM gregory.gauvain@inserm.fr; serge.picaud@inserm.fr
RI Dalkara, Deniz/D-5057-2017; Akolkar, Himanshu/AAV-4896-2021; Akolkar,
   Himanshu/ABG-1936-2021; Picaud, Serge/H-4012-2014
OI Dalkara, Deniz/0000-0003-4112-9321; Chavas, Joel/0000-0002-3559-5919;
   Picaud, Serge/0000-0002-0548-5145; Marre, Olivier/0000-0002-0090-6190
FU BPIfrance [2014-PRSP-15]; Gensight Biologics; Foundation Fighting
   Blindness; Federation des Aveugles de France; Agence Nationale de la
   Recherche [ANR-15-RHU-0001, ANR-10-LABX65, ANR-18-IAHU-0001,
   ANR-11-IDEX-0004-02]
FX We thank Matthew Chalk for critical proofreading. We thank Guillaume
   Labernede and Antoine Rizkallah for the manual counts of RGCs. This work
   was supported by BPIfrance (grant reference 2014-PRSP-15), Gensight
   Biologics, Foundation Fighting Blindness, Federation des Aveugles de
   France, and by French state funds managed by the Agence Nationale de la
   Recherche within the Investissements d'Avenir program, RHU LIGHT4DEAF
   (ANR-15-RHU-0001), LABEX LIFESENSES (ANR-10-LABX65), IHU FOReSIGHT
   (ANR-18-IAHU-0001), and (ANR-11-IDEX-0004-02).
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NR 64
TC 23
Z9 24
U1 3
U2 7
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
EI 2399-3642
J9 COMMUN BIOL
JI Commun. Biol.
PD JAN 27
PY 2021
VL 4
IS 1
AR 125
DI 10.1038/s42003-020-01594-w
PG 15
WC Biology; Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Life Sciences & Biomedicine - Other Topics; Science & Technology - Other
   Topics
GA SI3QJ
UT WOS:000654742200004
PM 33504896
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Garner, I
   Vichare, R
   Paulson, R
   Appavu, R
   Panguluri, SK
   Tzekov, R
   Sahiner, N
   Ayyala, R
   Biswal, MR
AF Garner, Inyoung
   Vichare, Riddhi
   Paulson, Ryan
   Appavu, Rajagopal
   Panguluri, Siva K.
   Tzekov, Radouil
   Sahiner, Nurettin
   Ayyala, Ramesh
   Biswal, Manas R.
TI Carbon Dots Fabrication: Ocular Imaging and Therapeutic Potential
SO FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
LA English
DT Review
DE anti-vegf; ocular imaging; quantum dots; carbon dots; nanoparticle;
   fundus imaging; anti-bacterial
ID DELIVERY; NANOPARTICLES; PROTEIN; AGENT
AB Vision loss is a major complication in common ocular infections and diseases such as bacterial keratitis, age-related macular degeneration (AMD) and diabetic retinopathy (DR). The prevalence of such ophthalmic diseases represents an urgent need to develop safe, effective, and long-term treatments. Current therapies are riddled with drawbacks and limitations which calls for the exploration of alternative drug delivery mechanisms. Toxicity of the inorganic metals and metal oxides used for drug delivery raise safety concerns that are alleviated with the alternate use of, a natural and organic polymer which is both biocompatible and environmentally friendly. Carbon dots (CDs) represent a great potential in novel biomedical applications due to their tunable fluorescence, biocompatibility, and ability to be conjugated with diverse therapeutic materials. There is a growing interest on the exploitation of these properties for drug delivery with enhanced bio-imaging. However, there are limited reports of CD applications for ophthalmic indications. In this review, we focus on the CD potential and the development of translational therapies for ophthalmic diseases. The current review presents better understanding of fabrication of CDs and how it may be useful in delivering anti-bacterial agents, anti-VEGF molecules as well as imaging for ophthalmic applications.
C1 [Garner, Inyoung; Vichare, Riddhi; Biswal, Manas R.] Univ S Florida, Dept Pharmaceut Sci, Taneja Coll Pharm, MSPN Grad Programs, Tampa, FL 33620 USA.
   [Paulson, Ryan; Appavu, Rajagopal; Panguluri, Siva K.; Biswal, Manas R.] Univ S Florida, Dept Pharmaceut Sci, Taneja Coll Pharm, Tampa, FL 33620 USA.
   [Tzekov, Radouil; Sahiner, Nurettin; Ayyala, Ramesh; Biswal, Manas R.] Univ S Florida, Dept Ophthalmol, Morsani Coll Med, Tampa, FL 33620 USA.
   [Sahiner, Nurettin] Canakkale Onsekiz Mart Univ, Dept Chem, Canakkale, Turkey.
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; Canakkale
   Onsekiz Mart University
RP Biswal, MR (通讯作者)，Univ S Florida, Dept Pharmaceut Sci, Taneja Coll Pharm, MSPN Grad Programs, Tampa, FL 33620 USA.; Biswal, MR (通讯作者)，Univ S Florida, Dept Pharmaceut Sci, Taneja Coll Pharm, Tampa, FL 33620 USA.; Biswal, MR (通讯作者)，Univ S Florida, Dept Ophthalmol, Morsani Coll Med, Tampa, FL 33620 USA.
EM biswal@usf.edu
RI Biswal, Manas/AAB-1514-2021
OI Biswal, Manas/0000-0002-9685-2923; Tzekov, Radouil/0000-0002-3662-9818
FU NIH/NEI [EY027013-02]; USF Taneja College of Pharmacy Start up grant
FX Supported by NIH/NEI award EY027013-02, USF Taneja College of Pharmacy
   Start up grant awarded to Dr. Manas R. Biswal.
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NR 43
TC 10
Z9 10
U1 1
U2 23
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 2296-4185
J9 FRONT BIOENG BIOTECH
JI Front. Bioeng. Biotechnol.
PD SEP 25
PY 2020
VL 8
AR 573407
DI 10.3389/fbioe.2020.573407
PG 7
WC Biotechnology & Applied Microbiology; Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Science & Technology - Other
   Topics
GA NY6BM
UT WOS:000576472400001
PM 33102456
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Hernandez, M
   Recalde, S
   Garcia-Garcia, L
   Bezunartea, J
   Miskey, C
   Johnen, S
   Diarra, S
   Sebe, A
   Rodriguez-Madoz, JR
   Pouillot, S
   Marie, C
   Izsvak, Z
   Scherman, D
   Kropp, M
   Prosper, F
   Thumann, G
   Ivics, Z
   Garcia-Layana, A
   Fernandez-Robredo, P
AF Hernandez, Maria
   Recalde, Sergio
   Garcia-Garcia, Laura
   Bezunartea, Jaione
   Miskey, Csaba
   Johnen, Sandra
   Diarra, Sabine
   Sebe, Attila
   Roberto Rodriguez-Madoz, Juan
   Pouillot, Severine
   Marie, Corinne
   Izsvak, Zsuzsanna
   Scherman, Daniel
   Kropp, Martina
   Prosper, Felipe
   Thumann, Gabriele
   Ivics, Zoltan
   Garcia-Layana, Alfredo
   Fernandez-Robredo, Patricia
TI Preclinical Evaluation of a Cell-Based Gene Therapy Using the Sleeping
   Beauty Transposon System in Choroidal Neovascularization
SO MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
LA English
DT Article
ID EPITHELIUM-DERIVED FACTOR; RETINAL-PIGMENT EPITHELIUM; ENDOTHELIAL
   GROWTH-FACTOR; MACULAR DEGENERATION; RETROVIRAL INTEGRATION; TISSUE
   INHIBITOR; SITE SELECTION; RCS RATS; IRIS; PEDF
AB Age-related macular degeneration (AMD) is a progressive retinal disorder characterized by imbalanced pro- and antiangiogenic signals. The aim of this study was to evaluate the effect of ex vivo cell-based gene therapy with stable expression of human pigment epithelium-derived factor (PEDF) release using the non-viral Sleeping Beauty (SB100X) transposon system delivered by miniplasmids free of antibiotic resistance markers (pFAR4). Retinal pigment epithelial (RPE) cells and iris pigment epithelial (IPE) cells were co-transfected with pFAR4-inverted terminal repeats (ITRs) CMV-PEDF-BGH and pFAR4-CMV-SB100X-SV40 plasmids. Laser-induced choroidal neovascularization (CNV) was performed in rats, and transfected primary cells (transfected RPE [tRPE] and transfected IPE [tIPE] cells) were injected into the subretinal space. The leakage and CNV areas, vascular endothelial growth factor (VEGF), PEDF protein expression, metalloproteinases 2 and 9 (MMP-2/9), and microglial/macrophage markers were measured. Injection with tRPE/IPE cells significantly reduced the leakage area at 7 and 14 days and the CNV area at 7 days. There was a significant increase in PEDF and the PEDF/VEGF ratio with tRPE cells and a reduction in the MMP-2 activity. Our data demonstrated that ex vivo non-viral gene therapy reduces CNV and could be an effective and safe therapeutic option for angiogenic retinal diseases.
C1 [Hernandez, Maria; Recalde, Sergio; Garcia-Garcia, Laura; Bezunartea, Jaione; Garcia-Layana, Alfredo; Fernandez-Robredo, Patricia] Clin Univ Navarra, Expt Ophthalmol Lab, IdiSNA, Ophthalmol, Pamplona, Spain.
   [Hernandez, Maria; Recalde, Sergio; Garcia-Garcia, Laura; Garcia-Layana, Alfredo; Fernandez-Robredo, Patricia] ISCIII, Oftared, Red Temat Invest Cooperat Sanitaria Enfermedades, Madrid, Spain.
   [Miskey, Csaba; Sebe, Attila; Ivics, Zoltan] Paul Ehrlich Inst, Div Med Biotechnol, D-63225 Langen, Germany.
   [Johnen, Sandra; Diarra, Sabine] Univ Hosp RWTH Aachen, Dept Ophthalmol, D-52074 Aachen, Germany.
   [Roberto Rodriguez-Madoz, Juan; Prosper, Felipe] Univ Navarra, Ctr Appl Med Res CIMA, IdiSNA, Regenerat Med Program, Pamplona 31008, Spain.
   [Pouillot, Severine] GenoSafe, F-91000 Evry, France.
   [Marie, Corinne; Scherman, Daniel] Univ Paris, INSERM, CNRS, UTCBS, F-75006 Paris, France.
   [Izsvak, Zsuzsanna] Helmholtz Assoc, Max Delbruck Ctr Mol Med, Berlin, Germany.
   [Izsvak, Zsuzsanna] Berlin Inst Hlth, Berlin, Germany.
   [Kropp, Martina; Thumann, Gabriele] Univ Geneva, Expt Ophthalmol, CH-1205 Geneva, Switzerland.
   [Kropp, Martina; Thumann, Gabriele] Univ Hosp Geneva, Dept Ophthalmol, CH-1205 Geneva, Switzerland.
   [Prosper, Felipe] Univ Navarra, Clin Univ Navarra, IdiSNA, Area Cell Therapy, Pamplona 31008, Spain.
   [Marie, Corinne] PSL Res Univ, Chim ParisTech, F-75005 Paris, France.
C3 University of Navarra; Instituto de Salud Carlos III; Paul Ehrlich
   Institute; RWTH Aachen University; RWTH Aachen University Hospital;
   University of Navarra; Centre National de la Recherche Scientifique
   (CNRS); Institut National de la Sante et de la Recherche Medicale
   (Inserm); UDICE-French Research Universities; Universite Paris Cite;
   Helmholtz Association; Max Delbruck Center for Molecular Medicine;
   Berlin Institute of Health; University of Geneva; University of Geneva;
   University of Navarra; UDICE-French Research Universities; PSL Research
   University Paris; Chimie ParisTech
RP Hernandez, M; Fernandez-Robredo, P (通讯作者)，Clin Univ Navarra, Expt Ophthalmol Lab, IdiSNA, Ophthalmol, Pamplona, Spain.
EM mahersan@unav.es; pfrobredo@unav.es
RI Pouillot, Severine/GQI-3574-2022; Johnen, Sandra/ABA-9955-2020;
   Rodriguez-Madoz, Juan Roberto/N-3667-2014; Miskey, Csaba/U-3473-2017;
   Sebe, Attila/GXV-5092-2022; Prosper, Felipe/H-6859-2017
OI Johnen, Sandra/0000-0003-0028-2557; Rodriguez-Madoz, Juan
   Roberto/0000-0003-4327-1866; Sebe, Attila/0000-0001-7814-5144; Prosper,
   Felipe/0000-0001-6115-8790; Scherman, Daniel/0000-0003-1207-1298; MARIE,
   Corinne/0000-0001-9619-5700
FU European Union [305134]; Fundacion Jesus Gangoiti Barrera; Fundacion
   Multiopticas (Spain); University of Navarra; Asociacion de Amigos de la
   Universidad de Navarra, Spain; European Research Council [ERC-2011-ADG
   294742]
FX This work was supported by the European Union's Seventh Framework
   Programme for research, technological development, and demonstration
   (grant agreement no. 305134) and Fundacion Jesus Gangoiti Barrera.
   Publication costs have been financed by Fundacion Multiopticas (Spain)
   within a collaborative project with the University of Navarra. L.G.-G.
   received a predoctoral grant from the Asociacion de Amigos de la
   Universidad de Navarra, Spain. Z. Izsvak was funded by European Research
   Council, ERC Advanced [ERC-2011-ADG 294742].
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NR 103
TC 7
Z9 7
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
EI 2329-0501
J9 MOL THER-METH CLIN D
JI Mol.Ther.-Methods Clin. Dev.
PD DEC 13
PY 2019
VL 15
BP 403
EP 417
DI 10.1016/j.omtm.2019.10.013
PG 15
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA JV7XB
UT WOS:000502573100037
PM 31890733
OA Green Accepted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Vasilyev, A
   Hansard, M
AF Vasilyev, A.
   Hansard, M.
TI Spatial Distribution of Eye-Movements After Central Vision Loss is
   Consistent with an Optimal Visual Search Strategy
SO INTERNATIONAL JOURNAL OF NEURAL SYSTEMS
LA English
DT Article
DE Oculomotor control; macular degeneration; visual search; Markov decision
   processes
ID EXPLORATION; OBJECTS; SCENES; MODEL
AB The problem of gaze allocation has previously been studied in the framework of eye-movement control models, which require prior knowledge of visibility maps (VMs). These encode the signal-to-noise ratio, at each point in the visual field, which can be used to define an optimal policy of gaze allocation. However, it is not always possible to estimate the VM, in a given experimental setting, as it depends on many factors, including the visual system of the individual observer. Hence, few eye-movement datasets include the corresponding VM estimates. This can be problematic for the analysis of certain clinical conditions, such as Age-related Macular Degeneration (AMD), which are associated with reduced sensitivity in the affected locations of the visual field. The corresponding VMs are highly idiosyncratic, and cannot be modeled by estimates obtained from healthy observers. We propose an algorithm for maximum likelihood VM estimation, working directly from eye-movement sequences. We apply this algorithm to two eye-tracking datasets, based on visual search tasks, obtained from AMD patients. We show that the inferred VMs are spatially consistent with the measured visual field sensitivities. We also show that simulations with the estimated VMs can account for the asymmetric distribution of saccade vectors, which is typical of AMD patients.
C1 [Vasilyev, A.; Hansard, M.] Queen Mary Univ London, Sch EECS, London E1 4NS, England.
C3 University of London; Queen Mary University London
RP Hansard, M (通讯作者)，Queen Mary Univ London, Sch EECS, London E1 4NS, England.
EM miles.hansard@qmul.ac.uk
FU EPSRC grant [EP/M01469X/1]
FX We thank Richard Bethlehem, Serge Dumoulin, Preeti Verghese and
   Christian Janssen for providing their eye-movement data sets and visual
   field measurements. This work was partially supported by EPSRC grant
   EP/M01469X/1.
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NR 39
TC 1
Z9 1
U1 0
U2 3
PU WORLD SCIENTIFIC PUBL CO PTE LTD
PI SINGAPORE
PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE
SN 0129-0657
EI 1793-6462
J9 INT J NEURAL SYST
JI Int. J. Neural Syst.
PD DEC
PY 2019
VL 29
IS 10
AR 1950026
DI 10.1142/S0129065719500266
PG 20
WC Computer Science, Artificial Intelligence
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science
GA JW4KN
UT WOS:000503022200005
PM 31711331
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Miura, M
   Makita, S
   Azuma, S
   Yasuno, Y
   Ueda, S
   Sugiyama, S
   Mino, T
   Yamaguchi, T
   Sandhu, HS
   Kaplan, HJ
   Iwasaki, T
   Goto, H
AF Miura, Masahiro
   Makita, Shuichi
   Azuma, Shinnosuke
   Yasuno, Yoshiaki
   Ueda, Shunichiro
   Sugiyama, Satoshi
   Mino, Toshihiro
   Yamaguchi, Tatsuo
   Sandhu, Harpal S.
   Kaplan, Henry J.
   Iwasaki, Takuya
   Goto, Hiroshi
TI Evaluation of focal damage in the retinal pigment epithelium layer in
   serous retinal pigment epithelium detachment
SO SCIENTIFIC REPORTS
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; HYPERREFLECTIVE FOCI; MACULAR
   DEGENERATION; CHOROIDAL MELANIN; POSTERIOR EYE; OCT; SEGMENTATION;
   PROGRESSION; LIPOFUSCIN; ATROPHY
AB The purpose of this study was to evaluate focal damage in the retinal pigment epithelium (RPE) layer in serous retinal pigment epithelium detachment (PED) with multi-contrast optical coherence tomography (OCT), which is capable of simultaneous measurement of OCT angiography, polarizationsensitive OCT and standard OCT images. We evaluated 37 eyes with age-related macular degeneration that had serous PED. Focal RPE damage was indicated by hyper-transmission beneath the RPE-Bruch's membrane band in standard OCT images. Distribution of RPE melanin was calculated using the dataset from multi-contrast OCT. Twenty-four points with hyper-transmission were detected in 21 of the 37 eyes. Standard OCT images failed to show disruption of the RPE-Bruch's membrane band at 5 of the 24 hyper-transmission points. Conversely, multi-contrast OCT images clearly showed melanin defects in the RPE-Bruch's membrane band at all points. Areas of melanin defects with disruption of the RPE-Bruch's membrane band were significantly larger than those without disruption. The volume of intraretinal hyper-reflective foci was significantly larger in eyes with hyper-transmission than that in eyes without hyper-transmission. Multi-contrast OCT is more sensitive than standard OCT for displaying changes at the RPE-Bruch's membrane band when there are small areas of RPE damage.
C1 [Miura, Masahiro; Ueda, Shunichiro; Iwasaki, Takuya] Tokyo Med Univ, Ibaraki Med Ctr, Dept Ophthalmol, Inashiki, Ibaraki, Japan.
   [Miura, Masahiro; Ueda, Shunichiro; Iwasaki, Takuya; Goto, Hiroshi] Tokyo Med Univ, Dept Ophthalmol, Tokyo, Japan.
   [Makita, Shuichi; Azuma, Shinnosuke; Yasuno, Yoshiaki] Univ Tsukuba, Computat Opt Grp, Tsukuba, Ibaraki, Japan.
   [Sugiyama, Satoshi] Tomey Corp, Nagoya, Aichi, Japan.
   [Mino, Toshihiro; Yamaguchi, Tatsuo] Topcon Corp, Tokyo, Japan.
   [Sandhu, Harpal S.; Kaplan, Henry J.] Univ Louisville, Dept Ophthalmol & Visual Sci, Louisville, KY 40292 USA.
C3 Tokyo Medical University; Tokyo Medical University; University of
   Tsukuba; Topcon Corporation; University of Louisville
RP Miura, M (通讯作者)，Tokyo Med Univ, Ibaraki Med Ctr, Dept Ophthalmol, Inashiki, Ibaraki, Japan.; Miura, M (通讯作者)，Tokyo Med Univ, Dept Ophthalmol, Tokyo, Japan.
EM m-miura@tokyo-med.ac.jp
RI Makita, Shuichi/G-3806-2011; Yasuno, Yoshiaki/F-2586-2011
OI Makita, Shuichi/0000-0002-6614-3640; kaplan, henry/0000-0003-1799-5692;
   Yasuno, Yoshiaki/0000-0003-1645-7948
FU Japan Society for the Promotion of Science, Tokyo, Japan [KAKENHI
   15K10905, 18K09460]; Research to Prevent Blindness [RPB-1944]
FX This study is supported by a Grant-in-Aid for Scientific Research
   (KAKENHI 15K10905 and 18K09460) from the Japan Society for the Promotion
   of Science, Tokyo, Japan. This study is supported in part by Research to
   Prevent Blindness (grant #RPB-1944). We thank Claire Barnes, PhD, from
   Edanz Group (www.edanzediting.com/ac) for editing a draft of this
   manuscript.
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NR 42
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Z9 10
U1 0
U2 2
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD MAR 1
PY 2019
VL 9
AR 3278
DI 10.1038/s41598-019-39688-z
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA HN1YW
UT WOS:000459983900084
PM 30824736
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Supharattanasitthi, W
   Carlsson, E
   Sharif, U
   Paraoan, L
AF Supharattanasitthi, Wasu
   Carlsson, Emil
   Sharif, Umar
   Paraoan, Luminita
TI CRISPR/Cas9-mediated one step bi-allelic change of genomic DNA in iPSCs
   and human RPE cells in vitro with dual antibiotic selection
SO SCIENTIFIC REPORTS
LA English
DT Article
ID SUSCEPTIBILITY; MANIPULATION; MUTATION
AB CRISPR/Cas9 causes double-stranded DNA breaks that can undergo DNA repair either via non-homologous end joining (NHEJ) or, in the presence of a template, homology-directed repair (HDR). HDR is typically used to insert a specific genetic modification into the genome but has low efficiency compared to NHEJ, which is lowered even further when trying to create a homozygous change. In this study we devised a novel approach for homozygous single base editing based on utilising simultaneously two donor DNA templates cloned in plasmids with different antibiotic resistant genes. The donor templates were co-transfected alongside the CRISPR/Cas9 machinery into cells and a double antibiotic selection was optimised and allowed the isolation of viable desired clones. We applied the method for obtaining isogenic cells homozygous for variant B cystatin C, a recessive risk factor for age-related macular degeneration and Alzheimer's disease, in both induced Pluripotent Stem Cells (iPSCs) and a human RPE cell line. Bi-allelic gene edited clones were validated by sequencing, demonstrating that the double antibiotic templates approach worked efficiently for both iPSCs and human differentiated cells. We propose that this one step gene editing approach can be used to improve the specificity and frequency of introducing homozygous modifications in mammalian cells.
C1 [Supharattanasitthi, Wasu; Carlsson, Emil; Sharif, Umar; Paraoan, Luminita] Univ Liverpool, Inst Ageing & Chron Dis, Dept Eye & Vis Sci, Liverpool, Merseyside, England.
   [Supharattanasitthi, Wasu] Mahidol Univ, Dept Physiol, Fac Pharm, Bangkok, Thailand.
C3 University of Liverpool; Mahidol University
RP Paraoan, L (通讯作者)，Univ Liverpool, Inst Ageing & Chron Dis, Dept Eye & Vis Sci, Liverpool, Merseyside, England.
EM lparaoan@liverpool.ac.uk
RI Paraoan, Luminita/K-1066-2016
OI Paraoan, Luminita/0000-0001-7568-7116; Supharattanasitthi,
   Wasu/0000-0003-3789-8312
FU Liverpool-Mahidol Partnership Scholarship; Macular Society; Humane
   Research Trust UK
FX WS is a recipient of a Liverpool-Mahidol Partnership Scholarship. The
   authors gratefully acknowledge the support from The Macular Society and
   The Humane Research Trust UK.
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NR 21
TC 13
Z9 14
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JAN 17
PY 2019
VL 9
AR 174
DI 10.1038/s41598-018-36740-2
PG 7
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA HH7ZS
UT WOS:000455951300022
PM 30655567
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Almotiri, J
   Elleithy, K
   Elleithy, A
AF Almotiri, Jasem
   Elleithy, Khaled
   Elleithy, Abdelrahman
TI Retinal Vessels Segmentation Techniques and Algorithms: A Survey
SO APPLIED SCIENCES-BASEL
LA English
DT Review
DE retinal vessels segmentation; matched filters; fuzzy expert systems;
   fuzzy c means; machine learning; adaptive thresholding; mathematical
   morphology; level set; vessel tracking; multi-scaling
ID BLOOD-VESSELS; MATCHED-FILTER; IMAGES; EXTRACTION; CONNECTIONS;
   RETINOPATHY; CURVATURE; KERNEL; MODEL
AB Retinal vessels identification and localization aim to separate the different retinal vasculature structure tissues, either wide or narrow ones, from the fundus image background and other retinal anatomical structures such as optic disc, macula, and abnormal lesions. Retinal vessels identification studies are attracting more and more attention in recent years due to non-invasive fundus imaging and the crucial information contained in vasculature structure which is helpful for the detection and diagnosis of a variety of retinal pathologies included but not limited to: Diabetic Retinopathy (DR), glaucoma, hypertension, and Age-related Macular Degeneration (AMD). With the development of almost two decades, the innovative approaches applying computer-aided techniques for segmenting retinal vessels are becoming more and more crucial and coming closer to routine clinical applications. The purpose of this paper is to provide a comprehensive overview for retinal vessels segmentation techniques. Firstly, a brief introduction to retinal fundus photography and imaging modalities of retinal images is given. Then, the preprocessing operations and the state of the art methods of retinal vessels identification are introduced. Moreover, the evaluation and validation of the results of retinal vessels segmentation are discussed. Finally, an objective assessment is presented and future developments and trends are addressed for retinal vessels identification techniques.
C1 [Almotiri, Jasem; Elleithy, Khaled] Univ Bridgeport, Comp Sci & Engn Dept, 126 Pk Ave, Bridgeport, CT 06604 USA.
   [Elleithy, Abdelrahman] William Paterson Univ, Dept Comp Sci, 300 Pompton Rd, Wayne, NJ 07470 USA.
C3 University of Bridgeport
RP Almotiri, J (通讯作者)，Univ Bridgeport, Comp Sci & Engn Dept, 126 Pk Ave, Bridgeport, CT 06604 USA.
EM jalmotir@my.bridgeport.edu; elleithy@bridgeport.edu; ElleithyA@wpunj.edu
RI Razaque, Abdul/AAC-4837-2020
OI Elleithy, Khaled/0000-0001-9239-5035; Almotiri,
   Jasem/0000-0002-7460-7257
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NR 125
TC 44
Z9 44
U1 2
U2 29
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 2076-3417
J9 APPL SCI-BASEL
JI Appl. Sci.-Basel
PD FEB
PY 2018
VL 8
IS 2
AR 155
DI 10.3390/app8020155
PG 31
WC Chemistry, Multidisciplinary; Engineering, Multidisciplinary; Materials
   Science, Multidisciplinary; Physics, Applied
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry; Engineering; Materials Science; Physics
GA FZ3SI
UT WOS:000427510300007
OA Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Gutierrez, MA
   Davis, SS
   Rosko, A
   Nguyen, SM
   Mitchell, KP
   Mateen, S
   Neves, J
   Garcia, TY
   Mooney, S
   Perdew, GH
   Hubbard, TD
   Lamba, DA
   Ramanathan, A
AF Gutierrez, Mark A.
   Davis, Sonnet S.
   Rosko, Andrew
   Nguyen, Steven M.
   Mitchell, Kylie P.
   Mateen, Samiha
   Neves, Joana
   Garcia, Thelma Y.
   Mooney, Shaun
   Perdew, Gary H.
   Hubbard, Troy D.
   Lamba, Deepak A.
   Ramanathan, Arvind
TI A novel AhR ligand, 2Al, protects the retina from environmental stress
SO SCIENTIFIC REPORTS
LA English
DT Article
ID ARYL-HYDROCARBON RECEPTOR; MACULAR DEGENERATION; OXIDATIVE STRESS;
   PIGMENT EPITHELIUM; CELL-DEATH; RPE CELLS; LIGHT EXPOSURE; BLUE-LIGHT;
   METABOLISM; EXPRESSION
AB Various retinal degenerative diseases including dry and neovascular age-related macular degeneration (AMD), retinitis pigmentosa, and diabetic retinopathy are associated with the degeneration of the retinal pigmented epithelial (RPE) layer of the retina. This consequently results in the death of rod and cone photoreceptors that they support, structurally and functionally leading to legal or complete blindness. Therefore, developing therapeutic strategies to preserve cellular homeostasis in the RPE would be a favorable asset in the clinic. The aryl hydrocarbon receptor (AhR) is a conserved, environmental ligand-dependent, per ARNT-sim (PAS) domain containing bHLH transcription factor that mediates adaptive response to stress via its downstream transcriptional targets. Using in silico, in vitro and in vivo assays, we identified 2,2'-aminophenyl indole (2Al) as a potent synthetic ligand of AhR that protects RPE cells in vitro from lipid peroxidation cytotoxicity mediated by 4-hydroxynonenal (4HNE) as well as the retina in vivo from light-damage. Additionally, metabolic characterization of this molecule by LC-MS suggests that 2Al alters the lipid metabolism of RPE cells, enhancing the intracellular levels of palmitoleic acid. Finally, we show that, as a downstream effector of 2Al-mediated AhR activation, palmitoleic acid protects RPE cells from 4HNE-mediated stress, and light mediated retinal degeneration in mice.
C1 [Gutierrez, Mark A.] Univ Denver, Colorado 2199 S Univ Blvd, Denver, CO 80208 USA.
   [Davis, Sonnet S.; Rosko, Andrew; Nguyen, Steven M.; Mitchell, Kylie P.; Mateen, Samiha; Neves, Joana; Garcia, Thelma Y.; Lamba, Deepak A.; Ramanathan, Arvind] Buck Inst Res Aging, 8001 Redwood Blvd, Novato, CA 94901 USA.
   [Mooney, Shaun] Univ Washington, Box 358047, Seattle, WA 98195 USA.
   [Perdew, Gary H.; Hubbard, Troy D.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, 309 Life Sci Bldg, University Pk, PA 16802 USA.
C3 University of Denver; Buck Institute for Research on Aging; University
   of Washington; University of Washington Seattle; Pennsylvania
   Commonwealth System of Higher Education (PCSHE); Pennsylvania State
   University; Pennsylvania State University - University Park
RP Lamba, DA; Ramanathan, A (通讯作者)，Buck Inst Res Aging, 8001 Redwood Blvd, Novato, CA 94901 USA.
EM dlamba@buckinstitute.org; aramanathan@buckinstitute.org
OI Gutierrez, Mark/0000-0001-8722-9462; Mendes Neves,
   Joana/0000-0002-1027-3489
FU Hillblom Foundation; NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
   [R01ES004869] Funding Source: NIH RePORTER
FX AR was funded by the Hillblom Foundation DL would like to thank Dato
   Fawziah Karim Foundation.
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NR 50
TC 16
Z9 19
U1 0
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUL 1
PY 2016
VL 6
AR 29025
DI 10.1038/srep29025
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA DP9XQ
UT WOS:000378851600001
PM 27364765
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Liu, J
   Copland, DA
   Theodoropoulou, S
   Chiu, HAA
   Barba, MD
   Mak, KW
   Mack, M
   Nicholson, LB
   Dick, AD
AF Liu, Jian
   Copland, David A.
   Theodoropoulou, Sofia
   Chiu, Hsi An Amy
   Barba, Miriam Durazo
   Mak, Ka Wang
   Mack, Matthias
   Nicholson, Lindsay B.
   Dick, Andrew D.
TI Impairing autophagy in retinal pigment epithelium leads to inflammasome
   activation and enhanced macrophage-mediated angiogenesis
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MACULAR DEGENERATION; NLRP3 INFLAMMASOME; ENDOTHELIAL-CELLS;
   AQUEOUS-HUMOR; EXPRESSION; DRUSEN; NEOVASCULARIZATION; INTERLEUKIN-6;
   MITOCHONDRIAL; INHIBITION
AB Age-related decreases in autophagy contribute to the progression of age-related macular degeneration (AMD). We have now studied the interaction between autophagy impaired in retinal pigment epithelium (RPE) and the responses of macrophages. We find that dying RPE cells can activate the macrophage inflammasome and promote angiogenesis. In vitro, inhibiting rotenone-induced autophagy in RPE cells elicits caspase-3 mediated cell death. Co-culture of damaged RPE with macrophages leads to the secretion of IL-1 beta, IL-6 and nitrite oxide. Exogenous IL-6 protects the dysfunctional RPE but IL-1 beta causes enhanced cell death. Furthermore, IL-1 beta toxicity is more pronounced in dysfunctional RPE cells showing reduced IRAK3 gene expression. Co-culture of macrophages with damaged RPE also elicits elevated levels of pro-angiogenic proteins that promote ex vivo choroidal vessel sprouting. In vivo, impaired autophagy in the eye promotes photoreceptor and RPE degeneration and recruitment of inflammasome-activated macrophages. The degenerative tissue environment drives an enhanced proangiogenic response, demonstrated by increased size of laser-induced choroidal neovascularization (CNV) lesions. The contribution of macrophages was confirmed by depletion of CCR2(+) monocytes, which attenuates CNV in the presence of RPE degeneration. Our results suggest that the interplay between perturbed RPE homeostasis and activated macrophages influences key features of AMD development.
C1 [Liu, Jian; Copland, David A.; Theodoropoulou, Sofia; Chiu, Hsi An Amy; Barba, Miriam Durazo; Mak, Ka Wang; Nicholson, Lindsay B.; Dick, Andrew D.] Univ Bristol, Sch Clin Sci, Bristol, Avon, England.
   [Liu, Jian; Copland, David A.; Nicholson, Lindsay B.; Dick, Andrew D.] Univ Bristol, Sch Cellular & Mol Med, Bristol, Avon, England.
   [Mack, Matthias] Univ Hosp Regensburg, Dept Internal Med 2, Regensburg, Germany.
   [Dick, Andrew D.] UCL, Inst Ophthalmol, London, England.
   [Dick, Andrew D.] NIHR, Biomed Res Ctr, London, England.
C3 University of Bristol; University of Bristol; University of Regensburg;
   University of London; University College London; University of London;
   King's College London
RP Dick, AD (通讯作者)，Univ Bristol, Sch Clin Sci, Bristol, Avon, England.; Dick, AD (通讯作者)，Univ Bristol, Sch Cellular & Mol Med, Bristol, Avon, England.; Dick, AD (通讯作者)，UCL, Inst Ophthalmol, London, England.; Dick, AD (通讯作者)，NIHR, Biomed Res Ctr, London, England.
EM a.dick@bristol.ac.uk
RI Copland, David/AAE-5334-2020; Copland, David/AAG-2368-2019
OI Copland, David/0000-0002-2257-4270; Theodoropoulou,
   Sofia/0000-0003-3038-5354; Dick, Andrew/0000-0002-0742-3159
FU National Eye Research Centre [RJ5818]; Rosetrees Trust [M418]; National
   Institute for Health Research [ACF-2013-25-003, CL-2015-25-502] Funding
   Source: researchfish; The Dunhill Medical Trust [R138/1109] Funding
   Source: researchfish
FX This work was supported by National Eye Research Centre (Grant No.
   RJ5818) and Rosetrees Trust (Grant No. M418). The authors wish to
   acknowledge Dr. Heping Xu (Queens University of Belfast, Belfast, UK)
   for providing the B6-RPE07 cell line; and the assistance of the Wolfson
   Bioimaging Facility at the University of Bristol.
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NR 67
TC 37
Z9 39
U1 1
U2 27
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 FEB 5
PY 2016
VL 6
AR 20639
DI 10.1038/srep20639
PG 15
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA DC9KY
UT WOS:000369541700001
PM 26847702
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Chen, GH
   Tzekov, R
   Li, WS
   Jiang, FZ
   Mao, SH
   Tong, YH
AF Chen, Guohai
   Tzekov, Radouil
   Li, Wensheng
   Jiang, Fangzheng
   Mao, Sihong
   Tong, Yuhua
TI Pharmacogenetics of Complement Factor H Y402H Polymorphism and Treatment
   of Neovascular AMD with Anti-VEGF Agents: A Meta-Analysis
SO SCIENTIFIC REPORTS
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; C-REACTIVE PROTEIN; MACULAR DEGENERATION;
   INTRAVITREAL RANIBIZUMAB; TREATMENT RESPONSE; ASSOCIATION; RISK; CFH;
   THERAPY; ANGIOGENESIS
AB The purpose of this study is to investigate whether the Y402H polymorphism (rs1061170, a T-to-C transition at amino acid position 402) in the complement factor H (CFH) gene have a pharmacogenetics effect on the anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (AMD). We performed a meta-analysis using databases including PubMed and EMBASE to find relevant studies. 13 published association studies were selected for this meta-analysis, including 2704 patients. For the CFH Y402H polymorphism, anti-VEGF treatment was much less effective in AMD patients with the CFH CC genotype (CC versus TT: odds ratio (OR) = 55, 95% confidence interval (CI), 0.31 to 0.95, P = 0.03; CC versus CT: OR = 0.60, 95% CI, 0.40 to 0.91, P = 0.02; and CC versus CT + TT: OR = 0.59, 95% CI, 0.38 to 0.90, P = 0.02, respectively). In subgroup analysis, CFH Y402H polymorphism was more likely to be a predictor of response for Caucasians (CC versus CT+ TT: OR = 0.63, 95% CI, 0.42 to 0.95, P = 0.03). In conclusion, pharmacogenetics of CFH Y402H polymorphism may play a role in response to anti-VEGF treatment for neovascular AMD, especially for Caucasians.
C1 [Chen, Guohai; Jiang, Fangzheng; Mao, Sihong; Tong, Yuhua] Quzhou Peoples Hosp, Dept Ophthalmol, Quzhou, Zhejiang, Peoples R China.
   [Tzekov, Radouil] Roskamp Inst, Sarasota, FL USA.
   [Tzekov, Radouil] Univ S Florida, Dept Ophthalmol, Tampa, FL USA.
   [Li, Wensheng] Xiamen Univ, Xiamen Eye Ctr, Xiamen, Fujian, Peoples R China.
C3 State University System of Florida; University of South Florida; Xiamen
   University
RP Li, WS (通讯作者)，Xiamen Univ, Xiamen Eye Ctr, Xiamen, Fujian, Peoples R China.
EM drlws@qq.com
OI Tzekov, Radouil/0000-0002-3662-9818
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NR 46
TC 23
Z9 25
U1 0
U2 5
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 SEP 28
PY 2015
VL 5
AR 14517
DI 10.1038/srep14517
PG 9
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA CS1EB
UT WOS:000361804300001
PM 26411831
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Morjaria, R
   Chong, NV
AF Morjaria, Rupal
   Chong, Ngai Victor
TI Pharmacokinetic evaluation of pegaptanib octasodium for the treatment of
   diabetic edema
SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
LA English
DT Review
DE diabetic macular edema; expert review; Macugen; pegaptanib octasodium
ID RANDOMIZED CONTROLLED-TRIAL; RANIBIZUMAB PLUS PROMPT; MACULAR EDEMA;
   DEFERRED LASER; FOLLOW-UP; TRIAMCINOLONE; RETINOPATHY; THERAPY; TYPE-1
AB Introduction: Diabetic macular edema (DME) is a leading cause of visual impairment in patients with diabetic retinopathy. Pegaptanib octasodium (Macugen) was the first anti-VEGF agent approved for the treatment of neovascular age-related macular degeneration. It is a selective anti-VEGF agent, which only blocks VEGF. It has been shown to be safe and effective in treatment of DME in randomized controlled trials and it may be a safer first-line treatment in patients with diabetes with a predisposition to cardiovascular risk factors.
   Areas covered: This review covers the pharmacokinetics of pegaptanib octasodium. The authors also evaluate pegaptanib octasodium's clinical efficacy, safety and tolerability in DME.
   Expert opinion: DME is the most common cause of visual loss in patients with diabetes. Pegaptanib has been found to be more effective than laser therapy alone for center-involving DME, its efficacy might be slightly worse than other pan-VEGF blockers, but the number of patients that have significant improvement of vision after treatment are similar to those treated with pan-VEGF blockers. As a selective VEGF blocker, it may have a better ocular and systemic safety profile than pan-VEGF blocking agents. It is reasonable to consider pegaptanib as the first-line treatment for center-involving DME with pan-VEGF blockers reserved for non-responders.
C1 [Morjaria, Rupal; Chong, Ngai Victor] Oxford Univ NHS Trust, Div Ophthalmol, Oxford OX3 9DY, England.
   [Morjaria, Rupal] Sandwell & West Birmingham NHS Trust, Div Ophthalmol, Birmingham B18 7QH, W Midlands, England.
C3 Oxford University Hospitals NHS Foundation Trust
RP Chong, NV (通讯作者)，Aston Univ, Birmingham B4 7ET, W Midlands, England.
EM victor@eretina.org
RI Chong, Victor/Q-6565-2018
OI Chong, Victor/0000-0002-7693-522X
FU Allergan; Novartis; Pfizer
FX V Chong is a consultant for Allergan, Bayer, Novartis and Quantel
   Medical. His department has received grant support from Allergan,
   Novartis and Pfizer. The authors have no other relevant affiliations or
   financial involvement with any organization or entity with a financial
   interest in or financial conflict with the subject matter or materials
   discussed in the manuscript apart from those disclosed.
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NR 35
TC 9
Z9 10
U1 0
U2 10
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1742-5255
EI 1744-7607
J9 EXPERT OPIN DRUG MET
JI Expert Opin. Drug Metab. Toxicol.
PD AUG
PY 2014
VL 10
IS 8
BP 1185
EP 1192
DI 10.1517/17425255.2014.922543
PG 8
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
GA AM7CK
UT WOS:000340022100010
PM 24856361
DA 2022-11-30
ER

PT J
AU Brown, MM
   Brown, GC
   Lieske, HB
   Lieske, PA
AF Brown, Melissa M.
   Brown, Gary C.
   Lieske, Heidi B.
   Lieske, P. Alexander
TI Financial return-on-investment of ophthalmic interventions: a new
   paradigm
SO CURRENT OPINION IN OPHTHALMOLOGY
LA English
DT Review
DE financial return-on-investment; increased national wealth;
   interventions; ophthalmologic; patient value gain; vitreoretinal
AB Purpose of reviewAlthough the patient value gain (improvement in quality-of-life and/or length-of-life) has been highlighted in Value-based Medicine cost-utility analyses, the financial value gain associated with healthcare interventions has received less emphasis. It is important for professional healthcare providers to realize their interventions often confer a large financial return-on-investment (ROI) to society.Recent findingsThe societal costs associated with vitreoretinal and other ophthalmic interventions include: direct ophthalmic medical costs expended (hospital, physician, drug, diagnostic testing and so forth), direct medical costs saved (decreased costs for depression, injury, skilled nursing facility, nursing home and others), direct nonmedical costs saved (decreased costs for caregivers, transportation, residence costs, moving costs, and others), and indirect medical costs saved (improving employment incidence and wages). The financial ROI for direct ophthalmic medical costs expended for ranibizumab therapy for neovascular age-related macular degeneration is 450%, whereas that for cataract surgery is 4500% and for medical open-angle glaucoma therapy is 4000%. Many costs gained add to the Gross Domestic Product and increase the wealth of the nation.SummaryMany vitreoretinal and other ophthalmologic interventions confer considerable patient value, but also result in a large financial ROI to society. This financial ROI increases the wealth of the nation.
C1 [Brown, Melissa M.; Brown, Gary C.; Lieske, Heidi B.; Lieske, P. Alexander] Ctr Value Based Med, Flourtown, PA 19031 USA.
   [Brown, Melissa M.] Thomas Jefferson Univ, Jefferson Med Coll, Wills Eye Hosp, Res Dept, Philadelphia, PA 19107 USA.
   [Brown, Melissa M.; Brown, Gary C.] Eye Res Inst, Philadelphia, PA USA.
   [Brown, Gary C.] Thomas Jefferson Univ, Jefferson Med Coll, Wills Eye Hosp, Retina Serv, Philadelphia, PA 19107 USA.
C3 Jefferson University; Jefferson University
RP Brown, MM (通讯作者)，Ctr Value Based Med, Box 335, Flourtown, PA 19031 USA.
EM mbrown@valuebasedmedicine.com
CR Actuaries at the Centers for Medicare and Medicaid Services, NAT HLTH EXP PROJ 20
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NR 18
TC 19
Z9 19
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8738
EI 1531-7021
J9 CURR OPIN OPHTHALMOL
JI Curr. Opin. Ophthalmol.
PD MAY
PY 2014
VL 25
IS 3
BP 171
EP 176
DI 10.1097/ICU.0000000000000040
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AF1GC
UT WOS:000334461400004
PM 24638114
DA 2022-11-30
ER

PT J
AU Mason, SL
   Stewart, RMK
   Kearns, VR
   Williams, RL
   Sheridan, CM
AF Mason, Sharon L.
   Stewart, Rosalind M. K.
   Kearns, Victoria R.
   Williams, Rachel L.
   Sheridan, Carl M.
TI Ocular epithelial transplantation: current uses and future potential
SO REGENERATIVE MEDICINE
LA English
DT Review
DE conjunctiva; epithelium; eye; limbus; ocular; progenitor; regeneration;
   retinal pigment epithelium; stem cells; transplantation
ID RETINAL-PIGMENT EPITHELIUM; LIMBAL STEM-CELLS; PUTATIVE STEM/PROGENITOR
   CELLS; IN-VITRO DIFFERENTIATION; ANTERIOR LENS CAPSULE; EX-VIVO
   EXPANSION; MACULAR DEGENERATION; AMNIOTIC MEMBRANE; SERUM-FREE;
   AUTOLOGOUS TRANSPLANTATION
AB Visual loss may be caused by a variety of ocular diseases and places a significant burden on society. Replacing or regenerating epithelial structures in the eye has been demonstrated to recover visual loss in a number of such diseases. Several types of cells (e.g., embryonic stem cells, adult stem/progenitor/differentiated epithelial cells and induced pluripotent cells) have generated much interest and research into their potential in restoring vision in a variety of conditions: from ocular surface disease to age-related macular degeneration. While there has been some success in clinical transplantation of conjunctival and particularly corneal epithelium utilizing ocular stem cells, in particular, from the limbus, the replacement of the retinal pigment epithelium by utilizing stem cell sources has yet to reach the clinic. Advances in our understanding of all of these cell types, their differentiation and subsequent optimization of culture conditions and development of suitable substrates for their transplantation will enable us to overcome current clinical obstacles. This article addresses the current status of knowledge concerning the biology of stem cells, their progeny and the use of differentiated epithelial cells to replace ocular epithelial cells. It will highlight the clinical outcomes to date and their potential for future clinical use.
C1 [Mason, Sharon L.; Stewart, Rosalind M. K.; Kearns, Victoria R.; Williams, Rachel L.; Sheridan, Carl M.] Univ Liverpool, Dept Eye & Vis Sci, Inst Ageing & Chron Dis, Liverpool L69 3GA, Merseyside, England.
C3 University of Liverpool
RP Sheridan, CM (通讯作者)，Univ Liverpool, Dept Eye & Vis Sci, Inst Ageing & Chron Dis, Daulby St, Liverpool L69 3GA, Merseyside, England.
EM carlos@liv.ac.uk
RI Sheridan, Carl/AAH-3607-2021; Kearns, Victoria/I-3271-2012
OI Sheridan, Carl/0000-0003-0100-9587; Kearns,
   Victoria/0000-0003-1426-6048; Williams, Rachel/0000-0002-1954-0256
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NR 165
TC 18
Z9 18
U1 0
U2 21
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
   1QB, ENGLAND
SN 1746-0751
EI 1746-076X
J9 REGEN MED
JI Regen. Med.
PD NOV
PY 2011
VL 6
IS 6
BP 767
EP 782
DI 10.2217/RME.11.94
PG 16
WC Cell & Tissue Engineering; Engineering, Biomedical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Engineering
GA 850NG
UT WOS:000297200900013
PM 22050528
DA 2022-11-30
ER

PT J
AU Liu, MM
   Tuo, JS
   Chan, CC
AF Liu, Melissa M.
   Tuo, Jingsheng
   Chan, Chi-Chao
TI Gene therapy for ocular diseases
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Review
ID EPITHELIUM-DERIVED FACTOR; CILIARY NEUROTROPHIC FACTOR; RETINAL
   GANGLION-CELLS; LEBER CONGENITAL AMAUROSIS; ADENOVIRUS-MEDIATED
   DELIVERY; RCS RAT MODEL; MOUSE MODEL; ADENOASSOCIATED VIRUS; TRANSGENE
   EXPRESSION; PHOTORECEPTOR DEGENERATION
AB The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.
C1 [Liu, Melissa M.; Tuo, Jingsheng; Chan, Chi-Chao] NEI, NIH, Immunopathol Sect, Immunol Lab, Bethesda, MD 20895 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI)
RP Chan, CC (通讯作者)，NEI, NIH, Immunopathol Sect, Immunol Lab, 10 Ctr Dr,Bldg 10,Rm 10N103, Bethesda, MD 20895 USA.
EM chanc@nei.nih.gov
OI Tuo, Jingsheng/0000-0002-1372-7810
FU NEI; American Health Assistance Foundation [M2007037]; National
   Institutes of Health; NATIONAL EYE INSTITUTE [T32EY007143, ZIAEY000418,
   ZIAEY000222] Funding Source: NIH RePORTER
FX This work was supported by the NEI Intramural Research Program and the
   American Health Assistance Foundation (M2007037). Other Funders:
   National Institutes of Health.
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NR 104
TC 61
Z9 64
U1 3
U2 30
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 2011
VL 95
IS 5
BP 604
EP 612
DI 10.1136/bjo.2009.174912
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 752TN
UT WOS:000289717300004
PM 20733027
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Scholl, S
   Kirchhof, J
   Augustin, AJ
AF Scholl, Stefan
   Kirchhof, Janna
   Augustin, Albert J.
TI Pathophysiology of Macular Edema
SO OPHTHALMOLOGICA
LA English
DT Article
DE Macular edema; Pathophysiology; Blood-retinal barrier; Vascular
   endothelial growth factor
ID PATHOGENESIS
AB Macular edema is defined as an accumulation of fluid in the outer plexiform layer and the inner nuclear layer as well as a swelling of Muller cells of the retina. It consists of a localized expansion of the retinal extracellular space (sometimes associated with the intracellular space) in the macular area. Macular edema is a common cause of a sudden or chronic decrease in visual acuity occurring in many ocular diseases such as age-related macular degeneration, diabetic retinopathy and retinal vein occlusion. As a nonspecific sign of many intraocular and systemic diseases, macular edema represents a common final pathway. The existence of the blood-retinal barrier (BRB) formed by intercellular junctions is the precondition required to maintain this physiological status. This status may become severely disturbed by many diseases, finally resulting in macular edema. In this article, the development of macular edema will also be classified by its pathophysiological and pathobiochemical pathways. Vascular components, the dysfunctional BRB, the role of proteins and water fluxes as well as the role of several inflammatory mediators (e.g. angiotensin II, vascular endothelial growth factor, prostaglandins) in the retina will be discussed as responsible mechanisms leading to the development of macular edema. Copyright (C) 2010 S. Karger AG, Basel
C1 [Kirchhof, Janna; Augustin, Albert J.] Stadt Klinikum Karlsruhe, Dept Ophthalmol, DE-76133 Karlsruhe, Germany.
   [Scholl, Stefan] Scholl & Augustin Augenarztl Privatpraxis, Baden Baden, Germany.
C3 Municipal Hospital Karlsruhe
RP Augustin, AJ (通讯作者)，Stadt Klinikum Karlsruhe, Dept Ophthalmol, Moltkestr 90, DE-76133 Karlsruhe, Germany.
EM albertjaugustin@googlemail.com
OI Augustin, Prof. Dr. Albert J./0000-0003-1591-0536
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NR 20
TC 86
Z9 95
U1 0
U2 6
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3755
EI 1423-0267
J9 OPHTHALMOLOGICA
JI Ophthalmologica
PY 2010
VL 224
SU 1
BP 8
EP 15
DI 10.1159/000315155
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 644VH
UT WOS:000281409000003
PM 20714176
DA 2022-11-30
ER

PT J
AU Krebs, I
   Binder, S
   Stolba, U
AF Krebs, Ilse
   Binder, Susanne
   Stolba, Ulrike
TI A new treatment regimen in combined intravitreal injection of
   triamcinolone acetonide and photodynamic therapy
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE triamcinolone acetonide; photodynamic therapy (PDT); choroidal
   neovascularisation (CNV); retinal angiomatous proliferation
ID CHOROIDAL NEOVASCULARIZATION
AB Combined photodynamic therapy (PDT) and intravitreal injection of triamcinolone acetonide is a new option in the treatment of the neovascular form of age-related macular degeneration. With the aim of increasing safety and efficacy we examined whether it is possible to administer the intravitreal injection prior to PDT.
   Patients with retinal angiomatous proliferation, who have an unfavourable prognosis when treated with PDT alone, were recruited to this study. Intravitreal injection of triamcinolone acetonide was applied 1 day before PDT. Distance acuity testing, retinal thickness measurement and fluorescein angiography were performed before treatment and 6 weeks and 3 months thereafter.
   Twenty-five patients were included: 18 were female, 7 male. Their mean age was 79 years. The distance acuity was 68 letters before treatment and at the follow-up examinations. The retinal thickness decreased significantly from mean 470.8 mu m to 335.4 mu m at week 6 and 360.8 mu m at month 3. At month 3, 48% showed signs of activity in the fluorescein angiography needing retreatment. Visualisation of the fundus was not reduced by the triamcinolone crystals.
   PDT was possible without difficulty after intravitreal injection of triamcinolone acetonide. Stabilisation of the visual acuity was possible, although only eyes with retinal angiomatous proliferation were included.
C1 Rudolf Fdn Clin, Dept Ophthalmol, A-1030 Vienna, Austria.
   Ludwig Boltzmann Inst Retinol & Biomicroscop Lase, A-1030 Vienna, Austria.
C3 Ludwig Boltzmann Institute
RP Krebs, I (通讯作者)，Rudolf Fdn Clin, Dept Ophthalmol, Jachgasse 25, A-1030 Vienna, Austria.
EM Ilse.Krebs@wienkav.at
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NR 10
TC 25
Z9 27
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013 USA
SN 0721-832X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD JUL
PY 2006
VL 244
IS 7
BP 863
EP 867
DI 10.1007/s00417-005-0155-8
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 065GO
UT WOS:000239148000016
PM 16331486
DA 2022-11-30
ER

PT J
AU Javaheri, M
   Hahn, DS
   Lakhanpal, RR
   Weiland, JD
   Humayun, MS
AF Javaheri, Michael
   Hahn, David S.
   Lakhanpal, Rohit R.
   Weiland, James D.
   Humayun, Mark S.
TI Retinal prostheses for the blind
SO ANNALS ACADEMY OF MEDICINE SINGAPORE
LA English
DT Review
DE age-related macular degeneration; artificial vision; retinal implants;
   retinitis pigmentosa
ID ELECTRICAL-STIMULATION; VISUAL PROSTHESIS; SUBRETINAL MICROPHOTODIODES;
   DEGENERATED PHOTORECEPTORS; MICROELECTRODE ARRAYS; RETINITIS-PIGMENTOSA;
   ARTIFICIAL VISION; RESTORE VISION; RABBIT RETINA; IMPLANTATION
AB Introduction: Using artificial means to treat extreme vision impairment has come closer to reality during the past few decades. The goal of this research has been to create an implantable medical device that provides useful vision for those patients who are left with no alternatives. Analogous to the cochlear implants for some forms of hearing loss, these devices could restore useful vision by converting visual information into patterns of electrical stimulation that excite the remaining viable inner retinal neurons in patients with retinitis pigmentosa or age-related macular degeneration. Methods: Data for this review were selected through a comprehensive literature search. Results: Advances in microtechnology have facilitated the development of a variety of prostheses that can be implanted in the visual cortex, around the optic nerve, or in the eye. Some of these approaches have shown the promise of providing useful visual input to patients with visual impairments. Conclusion: While the development of various retinal prostheses have shown promise in limited clinical trials, there are distinct advantages and disadvantages for each type of prosthesis. This review will focus primarily on the Epiretinal Intraocular Retinal Prosthesis, studied by our group, but will also briefly review other modalities: the subretinal prosthesis, cortical Prosthesis, and optic nerve prosthesis.
C1 Univ So Calif, Keck Sch Med, Dept Ophthalmol, Doheny Eye Inst,Doheny Retina Inst, Los Angeles, CA 90033 USA.
   Univ So Calif, Engn Res Ctr, Natl Sci Fdn Biomimet MicroElect Syst, BMES, Los Angeles, CA 90033 USA.
C3 Doheny Eye Institute; University of Southern California; National
   Science Foundation (NSF); University of Southern California
RP Humayun, MS (通讯作者)，Univ So Calif, Keck Sch Med, Dept Ophthalmol, Doheny Eye Inst,Doheny Retina Inst, 1450 San Pablo St Room 3600, Los Angeles, CA 90033 USA.
EM humayun@usc.edu
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NR 52
TC 51
Z9 55
U1 0
U2 14
PU ACAD MEDICINE SINGAPORE
PI REPUBLIC SINGAPORE
PA 142 NEIL RD, REPUBLIC SINGAPORE 088871, SINGAPORE
SN 0304-4602
J9 ANN ACAD MED SINGAP
JI Ann. Acad. Med. Singap.
PD MAR
PY 2006
VL 35
IS 3
BP 137
EP 144
PG 8
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 047SP
UT WOS:000237899300002
PM 16625261
DA 2022-11-30
ER

PT J
AU Feldman, T
   Ostrovskiy, D
   Yakovleva, M
   Dontsov, A
   Borzenok, S
   Ostrovsky, M
AF Feldman, Tatiana
   Ostrovskiy, Dmitriy
   Yakovleva, Marina
   Dontsov, Alexander
   Borzenok, Sergey
   Ostrovsky, Mikhail
TI Lipofuscin-Mediated Photic Stress Induces a Dark Toxic Effect on ARPE-19
   Cells
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE age-related macular degeneration; retinal pigment epithelium; lipofuscin
   granules; bisretinoid fluorophores; bisretinoid oxidation and
   degradation products; cytotoxicity
ID RETINAL-PIGMENT EPITHELIUM; GLYCATION END-PRODUCTS; LIGHT-INDUCED
   DAMAGE; AGE PIGMENT; OXIDATIVE STRESS; COMPLEMENT ACTIVATION; MACULAR
   DEGENERATION; RPE LIPOFUSCIN; A2E; INFLAMMATION
AB Lipofuscin granules from retinal pigment epithelium (RPE) cells contain bisretinoid fluorophores, which are photosensitizers and are phototoxic to cells. In the presence of oxygen, bisretinoids are oxidized to form various products, containing aldehydes and ketones, which are also potentially cytotoxic. In a prior study, we identified that bisretinoid oxidation and degradation products have both hydrophilic and amphiphilic properties, allowing their diffusion through the lipofuscin granule membrane into the RPE cell cytoplasm, and are thiobarbituric acid (TBA)-active. The purpose of the present study was to determine if these products exhibit a toxic effect to the RPE cell also in the absence of light. The experiments were performed using the lipofuscin-fed ARPE-19 cell culture. The RPE cell viability analysis was performed with the use of flow cytofluorimetry and laser scanning confocal microscopy. The results obtained indicated that the cell viability of the lipofuscin-fed ARPE-19 sample was clearly reduced not immediately after visible light irradiation for 18 h, but after 4 days maintaining in the dark. Consequently, we could conclude that bisretinoid oxidation products have a damaging effect on the RPE cell in the dark and can be considered as an aggravating factor in age-related macular degeneration progression.
C1 [Feldman, Tatiana; Ostrovsky, Mikhail] Lomonosov Moscow State Univ, Dept Biol, Leninskiye Gory 1, Moscow 119234, Russia.
   [Feldman, Tatiana; Yakovleva, Marina; Dontsov, Alexander; Ostrovsky, Mikhail] Russian Acad Sci, Emanuel Inst Biochem Phys, 4 Kosygin St, Moscow 119334, Russia.
   [Feldman, Tatiana; Ostrovskiy, Dmitriy; Yakovleva, Marina; Dontsov, Alexander; Ostrovsky, Mikhail] Russian Acad Sci, Koltzov Inst Dev Biol, 26 Vavilov St, Moscow 119334, Russia.
   [Ostrovskiy, Dmitriy; Borzenok, Sergey] Sv Fyodorov Eye Microsurg Complex, 59a Beskudnikovsky Bld, Moscow 127486, Russia.
C3 Lomonosov Moscow State University; Russian Academy of Sciences; Emanuel
   Institute of Biochemical Physics; Russian Academy of Sciences; Koltzov
   Institute of Developmental Biology of the Russian Academy of Sciences
RP Feldman, T (通讯作者)，Lomonosov Moscow State Univ, Dept Biol, Leninskiye Gory 1, Moscow 119234, Russia.; Feldman, T (通讯作者)，Russian Acad Sci, Emanuel Inst Biochem Phys, 4 Kosygin St, Moscow 119334, Russia.; Feldman, T (通讯作者)，Russian Acad Sci, Koltzov Inst Dev Biol, 26 Vavilov St, Moscow 119334, Russia.
EM feldmantb@mail.ru
RI Ostrovskiy, Dmitriy/ABA-9283-2020
OI Ostrovskiy, Dmitriy/0000-0002-2817-7102; Dontsov,
   Alexander/0000-0002-8367-5008
FU Ministry of Science and Higher Education of the Russian Federation
   [075-15-2020-773]
FX This research was funded by the Ministry of Science and Higher Education
   of the Russian Federation, grant number 075-15-2020-773.
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NR 76
TC 0
Z9 0
U1 0
U2 0
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD OCT
PY 2022
VL 23
IS 20
AR 12234
DI 10.3390/ijms232012234
PG 16
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA 5P3LY
UT WOS:000873057300001
PM 36293088
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Tolentino, MJ
   Tolentino, AJ
AF Tolentino, Michael J.
   Tolentino, Andrew J.
TI Investigational drugs in clinical trials for macular degeneration
SO EXPERT OPINION ON INVESTIGATIONAL DRUGS
LA English
DT Review
DE Macular degeneration; geographic atrophy; wet AMD; complement;
   macrophage; microglia; clinical trials
ID COMPLEMENT FACTOR-H; GEOGRAPHIC ATROPHY SECONDARY; POLYSIALIC ACID;
   SIALIC-ACID; APOLIPOPROTEIN-E; ANIMAL-MODEL; OUTER RETINA; TISSUE;
   MACROPHAGES; RANIBIZUMAB
AB Introduction Intravitreal anti-vascular endothelial growth factor (VEGF) injections for exudative age-related macular degeneration (eAMD) are effective and safe but require frequent injections and have nonresponding patients. Geographic atrophy/dry AMD (gaAMD) remains an unmet medical need. New therapies are needed to address this leading cause of blindness in the increasing aged population. Areas covered This paper reviews the pathogenesis of macular degeneration, current and failed therapeutics, therapies undergoing clinical trials and a rationale for why certain AMD therapies may succeed or fail. Expert Opinion VEGF-inhibitors reduce both vascular leakage and neovascularization. Experimental therapies that only address neovascularization or leakage will unlikely supplant anti-VEGF therapies. The most promising future therapies for eAMD, are those that target, more potently inhibit and have a more sustained effect on the VEGF pathway such as KSI-301, RGX-314, CLS-AX, EYEP-1901, OTX-TKI. GaAMD is a phenotype of phagocytic retinal cell loss. Inhibiting phagocytic activity of retinal microglial/macrophages at the border of geographic atrophy and reducing complement derived activators of microglial/macrophage is the most promising strategy. Complement inhibitors (Pegcetacoplan and Avacincaptad pegol) will likely obtain FDA approval but will serve to pave the way for combined complement and direct phagocytic inhibitors such as AVD-104.
C1 [Tolentino, Michael J.] Univ Cent Florida, Dept Ophthalmol, 401 South Florida Ave, Lakeland, FL 33803 USA.
   [Tolentino, Michael J.] Blue Ocean Clin Res, Lakeland, FL USA.
   [Tolentino, Michael J.; Tolentino, Andrew J.] Aviceda Therapeut, Cambridge, MA USA.
   [Tolentino, Andrew J.] Univ Calif Berkeley, Dept Biol, Berkeley, CA USA.
C3 State University System of Florida; University of Central Florida;
   University of California System; University of California Berkeley
RP Tolentino, MJ (通讯作者)，Univ Cent Florida, Dept Ophthalmol, 401 South Florida Ave, Lakeland, FL 33803 USA.
EM Mtolent88@me.com
FU Tolentino Eye Research Foundation, University of Central Florida, USA
FX This paper was funded by Tolentino Eye Research Foundation, University
   of Central Florida, USA.
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NR 154
TC 0
Z9 0
U1 3
U2 3
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1354-3784
EI 1744-7658
J9 EXPERT OPIN INV DRUG
JI Expert Opin. Investig. Drugs
PD OCT 3
PY 2022
VL 31
IS 10
BP 1067
EP 1085
DI 10.1080/13543784.2022.2113375
EA AUG 2022
PG 19
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 5I2KN
UT WOS:000855816000001
PM 35962560
OA hybrid
DA 2022-11-30
ER

PT J
AU Fayed, AE
   Baddar, D
   Estawro, RG
   Gerges, TK
AF Fayed, Alaa E.
   Baddar, Dina
   Estawro, Rania G.
   Gerges, Terese K.
TI Masking of macular neovascular membranes by subretinal hyperreflective
   material on optical coherence tomography angiography
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Age-related macular degeneration; fundus fluorescein angiography;
   macular neovascular membranes; optical coherence tomography angiography;
   subretinal hyperreflective material
ID RETINAL-PIGMENT EPITHELIUM; SWEPT-SOURCE; CHOROIDAL NEOVASCULARIZATION;
   SPECTRAL-DOMAIN; ULTRAHIGH-RESOLUTION; DEGENERATION; RANIBIZUMAB; TIME;
   PROLIFERATION; THERAPY
AB Purpose The purpose of this study was to determine whether subretinal hyperreflective material (SHRM) may mask the detection of macular neovascular membranes (MNV) on optical coherence tomography angiography (OCTA). Methods In this observational study, eyes with active neovascular age-related macular degeneration (nAMD), co-existing SHRM & intraretinal or subretinal fluid or hemorrhage on structural OCT, underwent OCTA & fundus fluorescein angiography (FFA) imaging. 6 x 6 mm choriocapillaris and outer retinal slabs on OCTA were examined to determine the presence of MNV underneath the SHRM. The corresponding area on FFA was used as a reference arm to confirm activity. Results Thirty eyes of thirty patients with SHRM and active nAMD were recruited. All eyes failed to show a MNV in the choriocapillaris & avascular slabs of the OCTA underneath the SHRM, but showed active hyperfluorescent MNVs that increased in size and intensity in the late stages of FFA. In one eye, parts of a MNV under the SHRM were undetectable due to signal attenuation, while parts extending beyond the SHRM were detected on the choriocapillaris en face slab with flow on the B scan. Conclusions SHRM may act as a reflecting surface that limits the passage of light waves in OCTA, creating areas of signal attenuation and diminishing its ability to detect underlying MNVs.
C1 [Fayed, Alaa E.] Cairo Univ, Kasr Al Ainy Sch Med, Dept Ophthalmol, Kasr Al Ainy St, Giza, Egypt.
   [Fayed, Alaa E.; Baddar, Dina; Estawro, Rania G.; Gerges, Terese K.] Watany Eye Hosp, Cairo, Egypt.
   [Baddar, Dina] Res Inst Ophthalmol, Giza, Egypt.
C3 Egyptian Knowledge Bank (EKB); Cairo University; Egyptian Knowledge Bank
   (EKB); General Organization of Teaching Hospitals & Institutes (GOTHI);
   Research Institute of Ophthalmology (RIO)
RP Fayed, AE (通讯作者)，Cairo Univ, Kasr Al Ainy Sch Med, Dept Ophthalmol, Kasr Al Ainy St, Giza, Egypt.
EM alaa.fayed@kasralainy.edu.eg
OI Baddar, Dina/0000-0001-9509-0624; Fayed, Alaa E./0000-0003-2634-3880
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NR 70
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 3547
EP 3555
AR 11206721221085396
DI 10.1177/11206721221085396
EA MAR 2022
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 4Z0VS
UT WOS:000765362600001
PM 35243925
DA 2022-11-30
ER

PT J
AU Yakovleva, M
   Dontsov, A
   Trofimova, N
   Sakina, N
   Kononikhin, A
   Aybush, A
   Gulin, A
   Feldman, T
   Ostrovsky, M
AF Yakovleva, Marina
   Dontsov, Alexander
   Trofimova, Natalia
   Sakina, Natalia
   Kononikhin, Alexey
   Aybush, Arseny
   Gulin, Alexander
   Feldman, Tatiana
   Ostrovsky, Mikhail
TI Lipofuscin Granule Bisretinoid Oxidation in the Human Retinal Pigment
   Epithelium forms Cytotoxic Carbonyls
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE age-related macular degeneration; retinal pigment epithelium; lipofuscin
   granules; bisretinoid fluorophores; bisretinoid oxidation products;
   cytotoxic carbonyls; hydrophilicity; amphiphilicity
ID LIGHT-INDUCED DAMAGE; RPE LIPOFUSCIN; AGE PIGMENT; MACULAR DEGENERATION;
   A2E; PRODUCTS; GLYCATION; STRESS; PHOTOOXIDATION; FLUOROPHORES
AB Age-related macular degeneration (AMD) is the primary cause of central blindness among the elderly. AMD is associated with progressive accumulation of lipofuscin granules in retinal pigment epithelium (RPE) cells. Lipofuscin contains bisretinoid fluorophores, which are photosensitizers and are phototoxic to RPE and neuroretinal cells. In the presence of oxygen, bisretinoids are also oxidized, forming various products, consisting primarily of aldehydes and ketones, which are also potentially cytotoxic. In a prior study, we identified that in AMD, bisretinoid oxidation products are increased in RPE lipofuscin granules. The purpose of the present study was to determine if these products were toxic to cellular structures. The physicochemical characteristics of bisretinoid oxidation products in lipofuscin, which were obtained from healthy donor eyes, were studied. Raman spectroscopy and time-of-flight secondary ion mass spectrometry (ToF-SIMS) analysis identified the presence of free-state aldehydes and ketones within the lipofuscin granules. Together, fluorescence spectroscopy, high-performance liquid chromatography, and mass spectrometry revealed that bisretinoid oxidation products have both hydrophilic and amphiphilic properties, allowing their diffusion through lipofuscin granule membrane into the RPE cell cytoplasm. These products contain cytotoxic carbonyls, which can modify cellular proteins and lipids. Therefore, bisretinoid oxidation products are a likely aggravating factor in the pathogenesis of AMD.
C1 [Yakovleva, Marina; Dontsov, Alexander; Trofimova, Natalia; Sakina, Natalia; Kononikhin, Alexey; Feldman, Tatiana; Ostrovsky, Mikhail] Russian Acad Sci, Emanuel Inst Biochem Phys, Kosygin St 4, Moscow 119334, Russia.
   [Kononikhin, Alexey] Skolkovo Inst Sci & Technol, Bolshoy Blvd 30,Bld 1, Moscow 121205, Russia.
   [Aybush, Arseny; Gulin, Alexander] Russian Acad Sci, NN Semenov Fed Res Ctr Chem Phys, Kosygin St 4,Bld 1, Moscow 119991, Russia.
   [Feldman, Tatiana; Ostrovsky, Mikhail] Lomonosov Moscow State Univ, Dept Biol, Leninskiye Gory 1, Moscow 119234, Russia.
C3 Russian Academy of Sciences; Emanuel Institute of Biochemical Physics;
   Skolkovo Institute of Science & Technology; Russian Academy of Sciences;
   N.N. Semenov Federal Research Centre for Chemical Physics, Russian
   Academy of Sciences; Lomonosov Moscow State University
RP Feldman, T (通讯作者)，Lomonosov Moscow State Univ, Dept Biol, Leninskiye Gory 1, Moscow 119234, Russia.
EM lina.invers@gmail.com; adontsovnick@yahoo.com; ntrofimova@mail.ru;
   nsakina@mail.ru; alex.kononikhin@gmail.com; aiboosh@gmail.com;
   aleksandr.gulin@phystech.edu; feldmantb@mail.ru; ostrosky3535@mail.ru
RI ; Feldman, Tatiana/F-2286-2014
OI Gulin, Alexander/0000-0001-7117-4276; Feldman,
   Tatiana/0000-0003-2613-056X; Kononikhin, Alexey/0000-0002-2238-3458
FU Ministry of Science and Higher Education of Russia [075-15-2020-795,
   13.1902.21.0027]
FX This research was funded by the Ministry of Science and Higher Education
   of Russia, grant number 075-15-2020-795 (local identifier
   13.1902.21.0027).
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NR 66
TC 1
Z9 1
U1 2
U2 6
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 2022
VL 23
IS 1
AR 222
DI 10.3390/ijms23010222
PG 15
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA ZB9FY
UT WOS:000757140300018
PM 35008647
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Zhao, NM
   Shi, JR
   Xu, HH
   Luo, Q
   Li, QY
   Liu, MZ
AF Zhao, Ningmin
   Shi, Jieran
   Xu, Haohang
   Luo, Qing
   Li, Qiaoyan
   Liu, Mingzhou
TI Baicalin suppresses glaucoma pathogenesis by regulating the PI3K/AKT
   signaling in vitro and in vivo
SO BIOENGINEERED
LA English
DT Article
DE Baicalin; glaucoma; autophagy; oxidative stress; PI3K; AKT signaling
ID RETINAL GANGLION-CELLS; OXIDATIVE STRESS; AUTOPHAGY; APOPTOSIS;
   EXCITOTOXICITY; IMPAIRMENT; DYNAMICS; PROTECTS; DAMAGE
AB Glaucoma, characterized with progressive degeneration of retinal ganglion cells (RGCs), is the second frequently leading cause of sight loss in the word after cataract. Baicalin plays a protective role in age-related macular degeneration, retinopathy of prematurity, branch retinal vein occlusion, and ischemia-induced neurodegeneration in the retina. The present study aimed to investigate the role of baicalin in glaucoma. RGCs were stimulated with N-methyl-D-aspartate (NMDA) to mimic the in vitro model of glaucoma. A mouse model of glaucoma induced by chronic elevated intraocular pressure was also established. The apoptosis, oxidative stress, and autophagy of RGCs were detected by flow cytometry analysis, 2,7-dichlorodihydrofluorescein diacetate staining, and Western blotting, respectively. Retinal pathological changes were exhibited by hemotoxylin and eosin staining. Baicalin restrained the NMDA-induced cell apoptosis, autophagy, and oxidative stress of RGCs by activating the PI3K/AKT signaling in vitro. The elevated intraocular pressure-induced pathological changes in retinas of glaucoma mice were attenuated by baicalin. Moreover, the number of RGCs was significantly decreased in glaucoma mice, and then increased by baicalin treatment. Baicalin also inhibited autophagy and activated PI3K/AKT signaling in vivo. In conclusion, baicalin suppresses glaucoma pathogenesis by regulating the PI3K/AKT signaling in vitro and in vivo.
C1 [Zhao, Ningmin; Shi, Jieran; Xu, Haohang; Luo, Qing; Li, Qiaoyan; Liu, Mingzhou] Zhengzhou Univ, Henan Prov Peoples Hosp, Dept Pharm, Peoples Hosp, Zhengzhou, Peoples R China.
C3 Zhengzhou University
RP Zhao, NM (通讯作者)，Zhengzhou Univ, Henan Prov Peoples Hosp, Peoples Hosp, 7 Weiwu Rd, Zhengzhou, Henan, Peoples R China.
EM znm188@188.com
FU Henan Medical Science and Technology Research Project [2018020395]
FX This work was supported by Henan Medical Science and Technology Research
   Project [no.2018020395].
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NR 50
TC 4
Z9 4
U1 8
U2 12
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 2165-5979
EI 2165-5987
J9 BIOENGINEERED
JI Bioengineered
PD DEC 20
PY 2021
VL 12
IS 2
BP 10187
EP 10198
DI 10.1080/21655979.2021.2001217
PG 12
WC Biotechnology & Applied Microbiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology
GA XI1IM
UT WOS:000725874600001
PM 34860641
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Di Paolo, M
AF Di Paolo, Mattia
TI Sequential PBM-Saffron Treatment in an Animal Model of Retinal
   Degeneration
SO MEDICINA-LITHUANIA
LA English
DT Article
DE retinal degeneration; oxidative stress; photobiomodulation; saffron;
   neuroprotection; synergistic effect
ID MACULAR DEGENERATION; LASER THERAPY; PHOTOBIOMODULATION; SENSITIVITY
AB Background and Objectives: Saffron treatment and photobiomodulation (PBM) are non-invasive therapeutic approaches able to mitigate and stabilize retinal degenerative diseases such as age-related macular degeneration (AMD). Although different, these therapies partially match their modulated pattern of genes. Recent attempts to find an additive effect by coadministration of saffron and PBM have failed. Instead, in this study, a different protocol to increase neuroprotection by providing consecutive saffron and PBM treatment administration is suggested. Materials and Methods: Albino rats, whose retinal damage was caused by light exposure (LD, light damage), were subjected to differential treatment protocols before and after LD: (1) PBM followed by saffron; and (2) single treatments of PBM. Thinning of the photoreceptor layer and neuro-inflammatory markers for gliosis and microglia were assessed via immune-histochemical techniques. Results: Results confirm that PBM and saffron alone cope with retinal neurodegenerative processes, preserving retinal thickness and gliosis and microglia invasion in a differential way. However, the synergistic effect of the combined treatment was restricted to the early neuroinflammation, even when provided sequentially. Conclusion: The broad spectra of action of both neuroprotectants require further investigation to identify other key pathways helpful in enhancing the effects of these two approaches in combination.
C1 [Di Paolo, Mattia] Univ Pisa, Dept Pharm, Via Bonanno 6, I-56121 Pisa, Italy.
   [Di Paolo, Mattia] Interuniv Consortium Biostruct & Biosyst Natl Ins, Via Medaglie dOro 305, I-00136 Rome, Italy.
   [Di Paolo, Mattia] Univ Aquila, Dept Biotechnol & Appl Clin Sci, Via Vetoio 1, I-67100 Laquila, Italy.
   [Di Paolo, Mattia] Bio Aurum Srl, Via Mangionello 12, I-73024 Maglie, Italy.
C3 University of Pisa; University of L'Aquila
RP Di Paolo, M (通讯作者)，Univ Pisa, Dept Pharm, Via Bonanno 6, I-56121 Pisa, Italy.; Di Paolo, M (通讯作者)，Interuniv Consortium Biostruct & Biosyst Natl Ins, Via Medaglie dOro 305, I-00136 Rome, Italy.; Di Paolo, M (通讯作者)，Univ Aquila, Dept Biotechnol & Appl Clin Sci, Via Vetoio 1, I-67100 Laquila, Italy.; Di Paolo, M (通讯作者)，Bio Aurum Srl, Via Mangionello 12, I-73024 Maglie, Italy.
EM m.dipaolo@bio-aurum.it
FU Hortus Novus srl; BIO-AURUM srl
FX The work presented in this article was partly funded by Hortus Novus srl
   and BIO-AURUM srl.
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NR 35
TC 2
Z9 2
U1 0
U2 3
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 1010-660X
EI 1648-9144
J9 MEDICINA-LITHUANIA
JI Med. Lith.
PD OCT
PY 2021
VL 57
IS 10
AR 1059
DI 10.3390/medicina57101059
PG 8
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA WM7OM
UT WOS:000711270500001
PM 34684096
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Ravi, R
   Kumaraswamy, A
   Chauhan, P
   Rajesh, BS
AF Ravi, Ramya
   Kumaraswamy, Anand
   Chauhan, Preeti
   Rajesh, Bharathidevi Subramaniam
TI Exogenous administration of hydrogen sulfide alleviates homocysteine
   induced inflammation in ARPE-19 cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE AMD; H2S; CBS; CSE; Inflammation
ID MACULAR DEGENERATION; HYPERHOMOCYSTEINEMIA; ATHEROSCLEROSIS;
   PATHOGENESIS; METABOLISM; APOPTOSIS; FOLATE
AB Plasma homocysteine (Hcy) is an independent risk factor for Age related macular degeneration (AMD) and an inducer of inflammation. Homocysteine catabolism releases hydrogen sulfide (H2S). H2S has controversial effects on inflammation. In this study we have analysed the endogenous and exogenous H2S in modulating inflammation using adult retinal pigment epithelial (ARPE-19) cells as an in vitro model for AMD. ARPE-19 cells were treated with various concentrations of Hcy (15, 30 and 50 mu M) for 3 h. Expression of Hcy transulfuration genes (CBS, CSE) by qPCR and western blot. H2S levels were measured using Free Radical Analyzer System (WPI, USA). The inflammatory markers (IL-6 and IL-8) were evaluated using real-time PCR and ELISA. Hcy exposure increased CBS protein expression, hydrogen sulfide levels and pro-inflammatory cytokines, modulating CBS by silencing did not alter H2S levels, but inhibition of CSE with PAG inhibited H2S production and decreased cytokine (IL-6 and IL-8) levels. On the contrary exogenous supply of hydrogen sulfide with NaHS and by compound 1c showed anti-inflammatory effects even in the presence of Hcy. This study shows that exogenous delivery of H2S decreases inflammation in retinal pigment epithelial cells on exposure to Hcy in ARPE-19 cells.
C1 [Ravi, Ramya; Kumaraswamy, Anand; Rajesh, Bharathidevi Subramaniam] Sankara Nethralaya, RS Mehta Jain Dept Biochem & Cell Biol, Vis Res Fdn, KBIRVO, Chennai 600006, Tamil Nadu, India.
   [Ravi, Ramya] SASTRA Deemed Univ, Sch Chem & Biotechnol, Thanjavur, India.
   [Chauhan, Preeti] Indian Inst Sci Educ & Res Pune, Dept Chem, Dr Homi Bhabha Rd, Pashan Pune 411008, Maharashtra, India.
C3 Shanmugha Arts, Science, Technology & Research Academy (SASTRA); Indian
   Institute of Science Education & Research (IISER) Pune
RP Rajesh, BS (通讯作者)，Sankara Nethralaya, RS Mehta Jain Dept Biochem & Cell Biol, Vis Res Fdn, KBIRVO, Chennai 600006, Tamil Nadu, India.
EM drbarathi@snmail.org
FU DBT [BT/PR8244/BRB/10/1219/2013]
FX The grant was provided by DBT: BT/PR8244/BRB/10/1219/2013.
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NR 49
TC 0
Z9 0
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 NOV
PY 2021
VL 212
AR 108759
DI 10.1016/j.exer.2021.108759
EA SEP 2021
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA UR8JP
UT WOS:000696988800003
PM 34499917
DA 2022-11-30
ER

PT J
AU Bhat, I
   Mamatha, BS
AF Bhat, Ishani
   Mamatha, Bangera Sheshappa
TI Genetic factors involved in modulating lutein bioavailability
SO NUTRITION RESEARCH
LA English
DT Review
DE Lutein; Zeaxanthin; Bioavailability; Nutrigenetics; Genetic-variability
ID IN-VITRO BIOACCESSIBILITY; BETA-CAROTENE; INTESTINAL-ABSORPTION; MACULAR
   PIGMENT; COGNITIVE FUNCTION; DOUBLE-BLIND; VISUAL FUNCTION;
   ALPHA-CAROTENE; PLASMA LUTEIN; VITAMIN-E
AB Lutein exhibits effective antioxidant activity conferring protective action against oxidative stress in age-related macular degeneration and cognitive decline. The inability to synthesize these compounds by the human body and the necessity to combat day-to-day oxidative stress prioritizes daily consumption of lutein. However, the bioavailability of the orally consumed lutein largely depends on its gastrointestinal absorption and subsequent metabolism which is in turn governed by various intrinsic and extrinsic factors. One of the most important yet least studied factors is the genetic make-up of an individual. The proteins that partake in the absorption, transportation, metabolism and excretion of lutein are encoded by the genes that experience inter-individual variability. Reports suggest that the unanimous effect of phenotypes resulting from such inter-individual variability in the genes of interest causes modulation of lutein bioavailability which is discussed in detail in this review article. However, despite the available reports, a community-based approach to a larger population is required to obtain a stronger understanding of the relationship between interindividual variability among these genes and lutein bioavailability. Such an understanding of nutrigenetics could not only pave a way to decipher mechanisms that modulate lutein bioavailability but also help in setting the dosage requirements of each patient. (c) 2021 Elsevier Inc. All rights reserved.
C1 [Bhat, Ishani; Mamatha, Bangera Sheshappa] Nitte Deemed Univ, Nitte Univ Ctr Sci Educ & Res NUCSER, Paneer Campus, Mangaluru 575018, Karnataka, India.
C3 NITTE (Deemed to be University); Nitte University Center for Science
   Education & Research (NUCSER)
RP Mamatha, BS (通讯作者)，Nitte Deemed Univ, Nitte Univ Ctr Sci Educ & Res NUCSER, Paneer Campus, Mangaluru 575018, Karnataka, India.
EM ishanibhat@gmail.com; mamatha.bs@nitte.edu.in
FU Indian Council of Medical Research, New Delhi, India
   [NUT/ADHOC/17/2019-2020]; Nitte (DU) [NURF1-2020]
FX The authors express their sincere gratitude to Prof. Dr. Praveen,
   Director (R&D) , Nitte (DU) and Prof. Dr. Anirban Chakraborty, Director
   (NUCSER) , Nitte (DU) for providing research facilities. The authors are
   grateful to Prof. Dr. Indrani Karunasagar, Director (DSTNUTEC) , Nitte
   (DU) and Prof. Dr. Iddya Karunasagar, Advisor (Research and Patent) ,
   Nitte (DU) for their constant support and guidance. The authors also
   extend their gratitude to Prof. KK Bhat, Former HOD, Sensory Science
   Dept., CFTRI, Mysore and Dr. Baskaran V, Dy. Director, CFTRI, Mysore for
   their valuable suggestions. The authors acknowledge the Indian Council
   of Medical Research (RCF No. NUT/ADHOC/17/20192020) , New Delhi, India
   and Nitte (DU) (Grant No. NURF1-2020) for funding this study.
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NR 63
TC 5
Z9 5
U1 2
U2 14
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0271-5317
EI 1879-0739
J9 NUTR RES
JI Nutr. Res.
PD JUL
PY 2021
VL 91
BP 36
EP 43
DI 10.1016/j.nutres.2021.04.007
EA JUN 2021
PG 8
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA TP6HC
UT WOS:000677697600004
PM 34134039
DA 2022-11-30
ER

PT J
AU Freilikhman, S
   Halasi, M
   Eran, A
   Adini, I
AF Freilikhman, Shirly
   Halasi, Marianna
   Eran, Alal
   Adini, Irit
TI Melanocytes determine angiogenesis gene expression across human tissues
SO PLOS ONE
LA English
DT Article
ID MACULAR DEGENERATION; RACIAL-DIFFERENCES; GENOME-WIDE; PIGMENTATION;
   CARE
AB Several angiogenesis-dependent diseases, including age-related macular degeneration and infantile hemangioma, display differential prevalence among Black, as compared to White individuals. Although socioeconomic status and genetic architecture have been suggested as explaining these differences, we have recently shown that pigment production per se might be involved. For example, we have shown that the extracellular protein fibromodulin is a pro-angiogenic factor highly secreted by melanocytes in White but not Black individuals. Still, additional pigment-dependent angiogenic factors and their molecular mechanisms remain to be identified. Understanding the contribution of pigmentation to angiogenesis in health and disease is essential for precision medicine of angiogenesis-dependent diseases with racial disparity. Toward that goal, we compared the transcriptomes of Black and White individuals in three tissues with angiogenic activity, namely artery, whole blood, and skin. We identified several differentially expressed angiogenesis pathways, including artery morphogenesis, regulation of endothelial cell chemotaxis, and cellular response to vascular endothelial growth factor stimulus. We then demonstrated that the expression of key genes in these pathways is directly modulated by the degree of pigmentation. We further identified the precise pigment production pathway controlling the expression of these genes, namely melanocortin 1 receptor (MC1R) signaling. These results demonstrate pigment-mediated regulation of angiogenesis-related pathways and their driver genes across human tissues.
C1 [Freilikhman, Shirly; Eran, Alal] Ben Gurion Univ Negev, Dept Life Sci, Beer Sheva, Israel.
   [Halasi, Marianna; Adini, Irit] Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Ctr Engn Med, Boston, MA 02115 USA.
   [Eran, Alal] Boston Childrens Hosp, Computat Hlth Informat Program, Boston, MA 02115 USA.
C3 Ben Gurion University; Harvard University; Harvard Medical School;
   Massachusetts General Hospital; Harvard University; Boston Children's
   Hospital
RP Eran, A (通讯作者)，Ben Gurion Univ Negev, Dept Life Sci, Beer Sheva, Israel.; Adini, I (通讯作者)，Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Ctr Engn Med, Boston, MA 02115 USA.; Eran, A (通讯作者)，Boston Childrens Hosp, Computat Hlth Informat Program, Boston, MA 02115 USA.
EM alal@bgu.ac.il; iadini@mgh.harvard.edu
OI Eran, Alal/0000-0001-6784-7597
FU US National Institutes of Health [NEI-5-RO1-EY024046]; Israeli Ministry
   of Science and Technology [17708]
FX This work was supported by US National Institutes of Health grant
   NEI-5-RO1-EY024046 to IA (https://www.nei.nih.gov). AE was supported by
   the Israeli Ministry of Science and Technology (grant no. 17708,
   https://www.gov.il/en/departments/ministry_of_science_and_technology).
   The funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
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NR 37
TC 1
Z9 1
U1 1
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 MAY 13
PY 2021
VL 16
IS 5
AR e0251121
DI 10.1371/journal.pone.0251121
PG 14
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA SW6MO
UT WOS:000664628200045
PM 33983985
OA gold, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Emri, E
   Kortvely, E
   Dammeier, S
   Klose, F
   Simpson, D
   den Hollander, AI
   Ueffing, M
   Lengyel, I
AF Emri, Eszter
   Kortvely, Elod
   Dammeier, Sascha
   Klose, Franziska
   Simpson, David
   den Hollander, Anneke I.
   Ueffing, Marius
   Lengyel, Imre
CA EYE-RISK Consortium
TI A Multi-Omics Approach Identifies Key Regulatory Pathways Induced by
   Long-Term Zinc Supplementation in Human Primary Retinal Pigment
   Epithelium
SO NUTRIENTS
LA English
DT Article
DE zinc; retinal pigment epithelium; age-related macular degeneration;
   transcriptome; proteome; secretome; gene set enrichment; TGFB1
ID MACULAR DEGENERATION; DEPOSIT FORMATION; BRUCHS MEMBRANE; BETA-CAROTENE;
   TISSUE FACTOR; VISION LOSS; AGE; DRUSEN; EXPRESSION; RPE
AB In age-related macular degeneration (AMD), both systemic and local zinc levels decline. Elevation of zinc in clinical studies delayed the progression to end-stage AMD. However, the molecular pathways underpinning this beneficial effect are not yet identified. In this study, we used differentiated primary human fetal retinal pigment epithelium (RPE) cultures and long-term zinc supplementation to carry out a combined transcriptome, proteome and secretome analysis from three genetically different human donors. After combining significant differences, we identified the complex molecular networks using Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA). The cell cultures from the three donors showed extensive pigmentation, development of microvilli and basal infoldings and responded to zinc supplementation with an increase in transepithelial electrical resistance (TEER) (apical supplementation: 443.2 +/- 79.3%, basal supplementation: 424.9 +/- 116.8%, compared to control: 317.5 +/- 98.2%). Significant changes were observed in the expression of 1044 genes, 151 cellular proteins and 124 secreted proteins. Gene set enrichment analysis revealed changes in specific molecular pathways related to cell adhesion/polarity, extracellular matrix organization, protein processing/transport, and oxidative stress response by zinc and identified a key upstream regulator effect similar to that of TGFB1.
C1 [Emri, Eszter; Simpson, David; Lengyel, Imre] Queens Univ Belfast, Wellcome Wolfson Inst Expt Med, Belfast BT9 7BL, Antrim, North Ireland.
   [Emri, Eszter; Kortvely, Elod] F Hoffmann La Roche Ltd, Roche Pharma Res & Early Dev Immunol Infect Dis &, Roche Innovat Ctr Basel, CH-4070 Basel, Switzerland.
   [Kortvely, Elod; Dammeier, Sascha; Klose, Franziska; Ueffing, Marius] Univ Tubingen, Inst Ophthalm Res, D-72076 Tubingen, Germany.
   [den Hollander, Anneke I.] Radboud Univ Nijmegen Med Ctr, Dept Ophthalmol, NL-6525 EX Nijmegen, Netherlands.
   [den Hollander, Anneke I.] Radboud Univ Nijmegen Med Ctr, Dept Genet, NL-6525 EX Nijmegen, Netherlands.
C3 Queens University Belfast; Roche Holding; Eberhard Karls University of
   Tubingen; Eberhard Karls University Hospital; Radboud University
   Nijmegen; Radboud University Nijmegen
RP Lengyel, I (通讯作者)，Queens Univ Belfast, Wellcome Wolfson Inst Expt Med, Belfast BT9 7BL, Antrim, North Ireland.
EM e.emri@qub.ac.uk; koertvely@roche.com; sascha.dammeier@web.de;
   franziska.klose@klinikum.uni-tuebingen.de; david.simpson@qub.ac.uk;
   anneke.denhollander@radboudumc.nl; marius.ueffing@uni-tuebingen.de;
   i.lengyel@qub.ac.uk
RI Lengyel, Imre/B-5217-2009; Emri, Eszter/ABE-9363-2020
OI Lengyel, Imre/0000-0001-7467-2174; Kortvely, Elod/0000-0003-1599-3116;
   den Hollander, Anneke/0000-0003-0634-5408; Simpson,
   David/0000-0003-0157-1211; Mones, Jordi/0000-0003-3685-2160
FU EYE-RISK project - European Union 's Horizon 2020 research and
   innovation program [634479]; F. Ho ffmann La Roche Ltd.
FX This work was supported by the EYE-RISK project funded by the European
   Union's Horizon 2020 research and innovation program under grant
   agreement no. 634479 and an unrestricted postdoctoral fellowship from F.
   Ho ffmann La Roche Ltd. (E.E.).
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NR 123
TC 6
Z9 6
U1 2
U2 7
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2072-6643
J9 NUTRIENTS
JI Nutrients
PD OCT
PY 2020
VL 12
IS 10
AR 3051
DI 10.3390/nu12103051
PG 24
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA OH8QZ
UT WOS:000582857600001
PM 33036197
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Vienola, KV
   Zhang, M
   Snyder, VC
   Sahel, JA
   Dansingani, KK
   Rossi, EA
AF Vienola, Kari V.
   Zhang, Min
   Snyder, Valerie C.
   Sahel, Jose-Alain
   Dansingani, Kunal K.
   Rossi, Ethan A.
TI Microstructure of the retinal pigment epithelium near-infrared
   autofluorescence in healthy young eyes and in patients with AMD
SO SCIENTIFIC REPORTS
LA English
DT Article
ID IN-VIVO FLUORESCENCE; FUNDUS AUTOFLUORESCENCE; LIGHT AUTOFLUORESCENCE;
   BLUE-LIGHT; HUMAN RPE; LIPOFUSCIN; CELLS; MELANIN
AB Retinal pigmented epithelial (RPE) cells are essential for maintaining normal visual function, especially in their role in the visual cycle, and are thought to be one of the first cell classes affected by age-related macular degeneration (AMD). Clinical imaging systems routinely evaluate the structure of the RPE at the tissue level, but cellular level information may provide valuable RPE biomarkers of health, aging and disease. In this exploratory study, participants were imaged with 795 nm excitation in adaptive optics scanning laser ophthalmoscopy (AOSLO) to observe the microstructure of the near-infrared autofluorescence (AO-IRAF) from the RPE layer in healthy retinas and patients with AMD. The expected hexagonal mosaic of RPE cells was only sometimes seen in normal eyes, while AMD patients exhibited highly variable patterns of altered AO-IRAF. In some participants, AO-IRAF structure corresponding to cones was observed, as we have demonstrated previously. In some AMD patients, marked alterations in the pattern of AO-IRAF could be seen even in areas where the RPE appeared relatively normal in clinical imaging modalities, such as spectral domain optical coherence tomography (SD-OCT). AO-IRAF imaging using AOSLO offers promise for better detection and understanding of early RPE changes in the course of AMD, potentially before clinical signs appear.
C1 [Vienola, Kari V.; Zhang, Min; Snyder, Valerie C.; Sahel, Jose-Alain; Dansingani, Kunal K.; Rossi, Ethan A.] Univ Pittsburgh, Sch Med, Dept Ophthalmol, Pittsburgh, PA 15213 USA.
   [Rossi, Ethan A.] Univ Pittsburgh, Swanson Sch Engn, Dept Bioengn, Pittsburgh, PA 15213 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); University
   of Pittsburgh; Pennsylvania Commonwealth System of Higher Education
   (PCSHE); University of Pittsburgh
RP Vienola, KV (通讯作者)，Univ Pittsburgh, Sch Med, Dept Ophthalmol, Pittsburgh, PA 15213 USA.
EM kvienola@pitt.edu
RI Vienola, Kari/ABE-7497-2021; Rossi, Ethan/AAC-6204-2019
OI Vienola, Kari/0000-0003-3390-392X; Rossi, Ethan/0000-0003-3210-0551
FU Edward N. & Della L. Thome Memorial Foundation; University of
   Pittsburgh; NIH CORE Grant [P30 EY08098]; Eye and Ear Foundation of
   Pittsburgh; NVIDIA GPU Grant Program; Research to Prevent Blindness, New
   York, N.Y., USA
FX This research was supported by a grant from the Edward N. & Della L.
   Thome Memorial Foundation to Jose Alain Sahel and by departmental
   startup funds from the University of Pittsburgh to Ethan A. Rossi. This
   work was also supported by NIH CORE Grant P30 EY08098 to the University
   of Pittsburgh Department of Ophthalmology, the Eye and Ear Foundation of
   Pittsburgh, NVIDIA GPU Grant Program and from an unrestricted grant from
   Research to Prevent Blindness, New York, N.Y., USA. The authors would
   like to thank Austin Roorda for sharing his AOSLO software with us,
   Pavan Tiruveedhula for electronics fabrication and software guidance and
   support, Jeff Speakman and Andrew Holmes for manufacturing custom
   mechanical components, David R. Williams and Qiang Yang for sharing
   their registration software and Jie Zhang, for sharing his original
   AOSLO optical design with us. Finally, the authors would like to thank
   Joseph Martel, Jay Chhablani & Marie-Helene Errera for their expertise
   interpreting the clinical images.
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NR 46
TC 11
Z9 10
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUN 12
PY 2020
VL 10
IS 1
AR 9561
DI 10.1038/s41598-020-66581-x
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA MD4VH
UT WOS:000543969200042
PM 32533046
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Vichare, R
   Garner, I
   Paulson, RJ
   Tzekov, R
   Sahiner, N
   Panguluri, SK
   Mohapatra, S
   Mohapatra, SS
   Ayyala, R
   Sneed, KB
   Biswal, MR
AF Vichare, Riddhi
   Garner, Inyoung
   Paulson, Ryan J.
   Tzekov, Radouil
   Sahiner, Nurettin
   Panguluri, Siva K.
   Mohapatra, Subhra
   Mohapatra, Shyam S.
   Ayyala, Ramesh
   Sneed, Kevin B.
   Biswal, Manas R.
TI Biofabrication of Chitosan-Based Nanomedicines and Its Potential Use for
   Translational Ophthalmic Applications
SO APPLIED SCIENCES-BASEL
LA English
DT Review
DE chitosan; nanoparticles; ocular diseases; biofabrication
ID SELF-AGGREGATED NANOPARTICLES; OCULAR DELIVERY; IN-VITRO;
   MOLECULAR-WEIGHT; CHITIN DEACETYLASE; HYALURONIC-ACID; SHRIMP;
   ENHANCEMENT; PREVALENCE; MECHANISM
AB Drug delivery to the anterior and posterior segment of eye remains a challenge. Nanoparticle-mediated drug delivery has indicated some promise. The presented review aims to summarize recent advancements in chitosan-based nanotherapies for ocular drug delivery and the challenges encountered during the process. Significant research using chitosan, a cationic linear polymer, is being conducted for ocular drug delivery. A vast number of publications exploit the mucoadhesive properties of the polymer, which arise due to interactions between the amino acids of chitosan and the sialic acid residues in mucous. The high degree of crosslinking in chitosan nanoparticles facilitates a dramatic increase in ocular drug retention of the desired drug, which subsequently helps in ocular penetration and improving the bioavailability of the drugs. A noted decrease in the initial burst of the drug is the basis for developing sustained drug release formulation using biodegradable and biocompatible chitosan polymer. In vitro as well as in vivo studies have indicated enhancement in the uptake, accumulation, and removal of chitosan nanoparticles from the site of delivery. In summary, chitosan- or modified-chitosan-based nanoparticles are being widely tested as drug carriers for treatment of bacterial and viral infections, glaucoma, age-related macular degeneration, and diabetic retinopathy.
C1 [Vichare, Riddhi; Garner, Inyoung; Mohapatra, Shyam S.; Biswal, Manas R.] Univ S Florida, Taneja Coll Pharm, MSPN Grad Programs, Tampa, FL 33612 USA.
   [Vichare, Riddhi; Garner, Inyoung; Paulson, Ryan J.; Tzekov, Radouil; Sahiner, Nurettin; Panguluri, Siva K.; Mohapatra, Shyam S.; Biswal, Manas R.] Univ S Florida, Taneja Coll Pharm, Dept Pharmaceut Sci, Tampa, FL 33612 USA.
   [Tzekov, Radouil; Sahiner, Nurettin; Ayyala, Ramesh; Biswal, Manas R.] Univ S Florida, Morsani Coll Med, Dept Ophthalmol, Tampa, FL 33612 USA.
   [Mohapatra, Subhra] Univ S Florida, Morsani Coll Med, Dept Mol Med, Tampa, FL 33612 USA.
   [Mohapatra, Shyam S.; Biswal, Manas R.] Univ S Florida, Morsani Coll Med, Dept Internal Med, Tampa, FL 33612 USA.
   [Sneed, Kevin B.] Univ S Florida, Taneja Coll Pharm, Dept Pharmacotherapeut & Clin Res, Tampa, FL 33612 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 South Florida; State
   University System of Florida; University of South Florida; State
   University System of Florida; University of South Florida
RP Biswal, MR (通讯作者)，Univ S Florida, Taneja Coll Pharm, MSPN Grad Programs, Tampa, FL 33612 USA.; 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.
EM vicharer@usf.edu; icho@usf.edu; rjpaulso@usf.edu; rtzekov@usf.edu;
   nsahiner@usf.edu; spangulu@usf.edu; smohapat@usf.edu; smohapa2@usf.edu;
   rayyala@usf.edu; ksneed@usf.edu; biswal@usf.edu
RI Biswal, Manas/AAB-1514-2021
OI Biswal, Manas/0000-0002-9685-2923; Tzekov, Radouil/0000-0002-3662-9818;
   Mohapatra, Shyam/0000-0001-5838-0681
FU NIH/NEI [EY027013-02]; USF Taneja College of Pharmacy Start up grant;
   USF Taneja College of Pharmacy MSPN graduate program
FX Supported by NIH/NEI award EY027013-02, USF Taneja College of Pharmacy
   Start up grant, and USF Taneja College of Pharmacy MSPN graduate program
   thesis supervision award provided to Manas R. Biswal.
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NR 90
TC 7
Z9 7
U1 1
U2 9
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2076-3417
J9 APPL SCI-BASEL
JI Appl. Sci.-Basel
PD JUN
PY 2020
VL 10
IS 12
AR 4189
DI 10.3390/app10124189
PG 17
WC Chemistry, Multidisciplinary; Engineering, Multidisciplinary; Materials
   Science, Multidisciplinary; Physics, Applied
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry; Engineering; Materials Science; Physics
GA MR3ZQ
UT WOS:000553529100001
OA gold
DA 2022-11-30
ER

PT J
AU Ibuki, M
   Shoda, C
   Miwa, Y
   Ishida, A
   Tsubota, K
   Kurihara, T
AF Ibuki, Mari
   Shoda, Chiho
   Miwa, Yukihiro
   Ishida, Ayako
   Tsubota, Kazuo
   Kurihara, Toshihide
TI Lactoferrin Has a Therapeutic Effect via HIF Inhibition in a Murine
   Model of Choroidal Neovascularization
SO FRONTIERS IN PHARMACOLOGY
LA English
DT Article
DE lactoferrin; age-related macular degeneration; laser-induced choroidal
   neovascularization; hypoxia-inducible factor; retina; retinal pigment
   epithelium; choroid
ID GROWTH; TRANSITION; MILK; MICE
AB Background
   Lactoferrin, a type of glycoprotein, is contained in exocrine fluids such as tears, breast milk, sweat, and saliva, and is known to have anti-microbial, antioxidant, and anti-cancer effects. In the ophthalmological field, topical administration of lactoferrin has been reported to have a therapeutic effect in a murine dry eye model. Hypoxia-inducible factor (HIF) regulates various gene expressions under hypoxia, including vascular endothelial growth factor (VEGF), and is considered as an alternative target for neovascular ocular diseases such as age-related macular degeneration (AMD). We previously screened natural products and identified lactoferrin as a novel HIF inhibitor. In this study, we confirmed that lactoferrin has an HIF inhibitory effect and a therapeutic effect in a murine model of neovascular AMD.
   Methods
   HIF inhibitory effects of lactoferrin were evaluated using a luciferase assay and western blotting in vitro. The quantified volume of choroidal neovascularization (CNV) induced by laser irradiation was compared with oral lactoferrin administration or conditional tissue specific Hif1a knockout mice.
   Results
   Lactoferrin administration showed a significant HIF inhibitory effect in the retinal neuronal cells. Oral administration of lactoferrin or conditional Hif1a gene deletion significantly reduced CNV volume compared to controls.
   Conclusions
   Lactoferrin has a therapeutic effect in a laser CNV model by suppressing the retinal HIF activity.
C1 [Ibuki, Mari; Shoda, Chiho; Miwa, Yukihiro; Ishida, Ayako; Tsubota, Kazuo; Kurihara, Toshihide] Keio Univ, Lab Photobiol, Sch Med, Tokyo, Japan.
   [Ibuki, Mari; Miwa, Yukihiro; Kurihara, Toshihide] Keio Univ, Dept Ophthalmol, Sch Med, Tokyo, Tokyo, Japan.
   [Shoda, Chiho] Nihon Univ, Dept Ophthalmol, Tokyo, Japan.
   [Tsubota, Kazuo] Tsubota Lab Inc, Tokyo, Japan.
C3 Keio University; Keio University; Nihon University
RP Tsubota, K; Kurihara, T (通讯作者)，Keio Univ, Lab Photobiol, Sch Med, Tokyo, Japan.; Kurihara, T (通讯作者)，Keio Univ, Dept Ophthalmol, Sch Med, Tokyo, Tokyo, Japan.; Tsubota, K (通讯作者)，Tsubota Lab Inc, Tokyo, Japan.
EM tsubota@z3.keio.jp; kurihara@z8.keio.jp
RI Kurihara, Toshihide/ABA-7058-2020; Tsubota, Kazuo/M-1915-2013
OI Kurihara, Toshihide/0000-0002-5457-2720; Tsubota,
   Kazuo/0000-0002-8874-7111; Miwa, Yukihiro/0000-0002-5377-6772
FU Ministry of Education, Culture, Sports, Science and Technology (MEXT)
   [15K10881, 18K09424]; ROHTO Pharmaceutical; ROHTO Pharmaceutical (Osaka,
   Japan)
FX This work was funded by Grants-in-Aid for Scientific Research (KAKENHI,
   number 15K10881 and 18K09424) from the Ministry of Education, Culture,
   Sports, Science and Technology (MEXT) to TK. This study was conducted
   with financial support from ROHTO Pharmaceutical. The authors declare
   that this study received funding from ROHTO Pharmaceutical (Osaka,
   Japan). The funder was not involved in the study design, collection,
   analysis, interpretation of data, the writing of this article or the
   decision to submit it for publication.
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NR 35
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Z9 12
U1 1
U2 2
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 1663-9812
J9 FRONT PHARMACOL
JI Front. Pharmacol.
PD FEB 28
PY 2020
VL 11
AR 174
DI 10.3389/fphar.2020.00174
PG 11
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA LC7NT
UT WOS:000525520200001
PM 32180725
OA Green Published, gold
DA 2022-11-30
ER

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   Simkiss, Philippa
   Zambarakji, Hadi
TI Eye clinic liaison officers service in the United Kingdom
SO INTERNATIONAL JOURNAL OF HEALTH PLANNING AND MANAGEMENT
LA English
DT Article
DE ECLO; macular degeneration; registration; sight impairment; support
ID DEPRESSION
AB Background To investigate the role of eye clinic liaison officers (ECLOs) in the United Kingdom and analyse patients' demographics and services provided. Methods This is a retrospective observational study. Data were collected from the Royal National Institute of Blind People for ECLOs in Wales, Scotland, Northern Ireland and England for the first quarter of 2015. Statistical analysis was performed using chi-square and t test as appropriate. Results Trusts with ECLOs support vary greatly in the UK regions. Only one-third of NHS trusts in England have an ECLO service. Over 4000 patients were assessed. The majority of patients were of White ethnic background (94%), lived alone (37%), had no carers (58%) and were in their 80s (29.5%). The principal ocular conditions causing sight loss and certification were age-related macular degeneration (41.6%) and glaucoma (18.1%). Approximately 70% of patients are first seen at 13 to 18 months from diagnosis. Conclusions ECLO services vary in the UK regions. England has the lowest ECLO availability per trust and the majority of those assessed were of White British origin with AMD. There are significant delays from diagnosis to the first visit indicating the need for improved services. Further studies are necessary to develop the evidence base for the expansion and funding of ECLO services.
C1 [Papastefanou, Vasilios P.; Kang, Swan; Zambarakji, Hadi] Whipps Cross Univ Hosp, Eye Treatment Ctr, Barts Hlth, London, England.
   [Simkiss, Philippa] Royal Natl Inst Blind People RNIB, London, England.
C3 Barts Health NHS Trust; University of London; Queen Mary University
   London
RP Zambarakji, H (通讯作者)，Barts Hlth NHS Trust, Eye Treatment Ctr, Whipps Cross Univ Hosp, London E11 1NR, England.
EM hzambarakji@me.com
RI Zambarakji, Hadi/AAM-6095-2020; PAPASTEFANOU, VASILIOS/AAN-9779-2020
OI Papastefanou, Vasilios/0000-0001-8055-6911; Zambarakji,
   Hadi/0000-0002-7968-0234; Simkiss, Philippa/0000-0002-9557-7536
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NR 9
TC 2
Z9 2
U1 1
U2 4
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0749-6753
EI 1099-1751
J9 INT J HEALTH PLAN M
JI Int. J. Health Plan. Manag.
PD MAR
PY 2020
VL 35
IS 2
BP 506
EP 519
DI 10.1002/hpm.2938
EA NOV 2019
PG 14
WC Health Policy & Services; Public, Environmental & Occupational Health
WE Social Science Citation Index (SSCI)
SC Health Care Sciences & Services; Public, Environmental & Occupational
   Health
GA KU6OX
UT WOS:000496427800001
PM 31729071
DA 2022-11-30
ER

PT J
AU Lyssenko, NN
   Haider, N
   Picataggi, A
   Cipollari, E
   Jiao, WZ
   Phillips, MC
   Rader, DJ
   Chavali, VRM
AF Lyssenko, Nicholas N.
   Haider, Naqi
   Picataggi, Antonino
   Cipollari, Eleonora
   Jiao, Wanzhen
   Phillips, Michael C.
   Rader, Daniel J.
   Chavali, Venkata Ramana Murthy
TI Directional ABCA1-mediated cholesterol efflux and apoB-lipoprotein
   secretion in the retinal pigment epithelium
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE adenosine triphosphate-binding cassette transporter A1; apolipoprotein
   B; high density lipoproteins; oxidized lipids; age-related macular
   degeneration; soft drusen; subretinal drusenoid deposits; cell
   polarization
ID HIGH-DENSITY-LIPOPROTEIN; SUBRETINAL DRUSENOID DEPOSITS; AGE-RELATED
   MACULOPATHY; HUMAN BRUCHS MEMBRANE; MACULAR DEGENERATION; RPE CELLS;
   SR-BI; CELLULAR CHOLESTEROL; APOLIPOPROTEIN AI; LIPID-METABOLISM
AB Cholesterol-containing soft drusen and subretinal drusenoid deposits (SDDs) occur at the basolateral and apical side of the retinal pigment epithelium (RPE), respectively, in the chorioretina and are independent risk factors for late age-related macular degeneration (AMD). Cholesterol in these deposits could originate from the RPE as nascent HDL or apoB-lipoprotein. We characterized cholesterol efflux and apoB-lipoprotein secretion in RPE cells. Human RPE cells, ARPE-19, formed nascent HDL that was similar in physicochemical properties to nascent HDL formed by other cell types. In highly polarized primary human fetal RPE (phfRPE) monolayers grown in low-lipid conditions, cholesterol efflux to HDL was moderately directional to the apical side and much stronger than ABCA1-mediated efflux to apoA-I at both sides; ABCA1-mediated efflux was weak and equivalent between the two sides. Feeding phfRPE monolayers with oxidized or acetylated LDL increased intracellular levels of free and esterified cholesterol and substantially raised ABCA1-mediated cholesterol efflux at the apical side. phfRPE monolayers secreted apoB-lipoprotein preferentially to the apical side in low-lipid and oxidized LDL-feeding conditions. These findings together with evidence from human genetics and AMD pathology suggest that RPE-generated HDL may contribute lipid to SDDs.
C1 [Lyssenko, Nicholas N.; Picataggi, Antonino; Cipollari, Eleonora; Phillips, Michael C.; Rader, Daniel J.] Univ Penn, Dept Med, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA.
   [Haider, Naqi; Jiao, Wanzhen; Chavali, Venkata Ramana Murthy] Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Philadelphia, PA 19104 USA.
   [Rader, Daniel J.] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; University of Pennsylvania; Pennsylvania
   Medicine; University of Pennsylvania; Pennsylvania Medicine
RP Lyssenko, NN (通讯作者)，Univ Penn, Dept Med, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA.; Chavali, VRM (通讯作者)，Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Philadelphia, PA 19104 USA.
EM nilys@pennmedicine.upenn.edu; vchavali@pennmedicine.upenn.edu
FU American Heart Association [14SDG20230024]; National Eye Institute
   [1R21EY028273-01A1, P30 EY01583-26]; Genentech Age-related Macular
   Degeneration Fellowship; BrightFocus Foundation [M2013122]; Research to
   Prevent Blindness; F. M. Kirby Foundation; Paul MacKall and Evanina Bell
   MacKall Trust; NATIONAL EYE INSTITUTE [P30EY001583, R21EY028273] Funding
   Source: NIH RePORTER
FX This work was supported by American Heart Association Scientist
   Development Grant 14SDG20230024 (N.N.L.), National Eye Institute Grant
   1R21EY028273-01A1 (V.R.M.C.), National Eye Institute Vision Core Grant
   P30 EY01583-26 (V.R.M.C.), a Genentech Age-related Macular Degeneration
   Fellowship (V.R.M.C.), BrightFocus Foundation Grant M2013122 (V.R.M.C.),
   Research to Prevent Blindness Unrestricted Grant Funds to Scheie Eye
   Institute, the F. M. Kirby Foundation (V.R.M.C.), and the Paul MacKall
   and Evanina Bell MacKall Trust (V.R.M.C.).
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NR 77
TC 15
Z9 16
U1 0
U2 3
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0022-2275
EI 1539-7262
J9 J LIPID RES
JI J. Lipid Res.
PD OCT
PY 2018
VL 59
IS 10
BP 1927
EP 1939
DI 10.1194/jlr.M087361
PG 13
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA GU6RY
UT WOS:000445444500012
PM 30076206
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Pascual-Pineda, LA
   Bautista-Hernandez, S
   Pascual-Mathey, LI
   Flores-Andrade, E
   Jimenez, M
   Beristain, CI
AF Pascual-Pineda, L. A.
   Bautista-Hernandez, S.
   Pascual-Mathey, L., I
   Flores-Andrade, E.
   Jimenez, M.
   Beristain, C., I
TI DEVELOPMENT OF PAPRIKA OLEORESIN DISPERSIONS FOR IMPROVING THE
   BIOACCESSIBILITY OF CAROTENOIDS
SO REVISTA MEXICANA DE INGENIERIA QUIMICA
LA English
DT Article
DE nanoemulsions; paprika oleoresin; gastrointestinal tract;
   bioaccessibility
ID IN-WATER MICROEMULSIONS; BETA-CAROTENE; OIL; EMULSIONS; DELIVERY;
   STABILITY; BEHAVIOR; SYSTEMS; DESIGN; FOODS
AB Red pepper (Capsicum annuum L.) oleoresin contain a diversity of carotenoids, which has been associated with lower risk for different chronic diseases like various types of cancer, cardiovascular disease and age-related macular degeneration. However, they are very sensitive to pro-oxidant conditions, heat and light. Previous attempts have been made to improve bioavailability and stability of carotenoids, of which emulsions have proven to be a feasible method. Conventional (CE) and nano (NE) emulsions loaded with paprika oleoresin carotenoids (POC; 1% wt/wt) were fabricated using surfactants blend (Tween 40 and Span 20) with a hydrophilic-lipophilic balance (HLB), ranging from 12 to 15.6, and surfactant: POC ratio of 1:1 (wt/wt). POC bioaccessibility was studied using an in vitro model to simulate oral, gastric and small intestine phases of the gastrointestinal tract (GIT). In general, higher HLB values produced CE's and NE's with smaller particle size and negative value of zeta potential. The smaller the droplet size, the higher was POC bioaccessibility. NE prepared with a HLB of 15.6 had a particle size of 38.93 nm and a bioaccessibility of 74%. Bioaccessibility of unemulsified POC was practically nil. Conventional and nanoemulsions protected paprika oleoresin carotenoids deterioration during simulated gastrointestinal tract.
C1 [Pascual-Pineda, L. A.] Univ Veracruzana, Unidad Serv Apoyo Resolut Analit SARA, Av Dr Rafael Sanchez Altamirano S-N, Xalapa 91000, Veracruz, Mexico.
   [Bautista-Hernandez, S.; Flores-Andrade, E.] Univ Veracruzana, Fac Ciencias Quim, Prolongac Oriente 6, Orizaba 94340, Veracruz, Mexico.
   [Pascual-Mathey, L., I] Univ Veracruzana, Fac QFB, Circuito Gonzalo Aguirre Beltran S-N, Xalapa 91000, Veracruz, Mexico.
   [Jimenez, M.; Beristain, C., I] Univ Veracruzana, Inst Ciencias Basicas, Av Dr Rafael Sanchez Altamirano S-N, Xalapa 91000, Veracruz, Mexico.
C3 Universidad Veracruzana; Universidad Veracruzana; Universidad
   Veracruzana; Universidad Veracruzana
RP Beristain, CI (通讯作者)，Univ Veracruzana, Inst Ciencias Basicas, Av Dr Rafael Sanchez Altamirano S-N, Xalapa 91000, Veracruz, Mexico.
EM lpascual@uv.mx; lupascual@uv.mx
RI Flores-Andrade, Enrique/AAD-3365-2019
OI Flores-Andrade, Enrique/0000-0003-3182-868X; Pascual,
   Luz/0000-0001-5150-3140; Pascual Pineda, Luz Alicia/0000-0002-2737-282X;
   Jimenez-Fernandez, Maribel/0000-0001-5437-3812
FU Consejo Nacional de Ciencia y Tecnologia [252692]
FX The authors wish to thank the Consejo Nacional de Ciencia y Tecnologia
   for the support received through the grant 252692.
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NR 34
TC 5
Z9 5
U1 0
U2 7
PU UNIV AUTONOMA METROPOLITANA-IZTAPALAPA
PI MEXICO
PA C/O DR JAIME VERNON-CARTER, SAN RAFAEL ATLIXCO NO 186, COL VICENTINA,
   DELEGACION IZTAPALAPA, MEXICO, 09340, MEXICO
SN 1665-2738
J9 REV MEX ING QUIM
JI Rev. Mex. Ing. Quim.
PD AUG
PY 2018
VL 17
IS 2
BP 767
EP 776
DI 10.24275/uam/izt/dcbi/revmexingquim/2018v17n2/Pascual
PG 10
WC Chemistry, Applied; Engineering, Chemical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry; Engineering
GA GW5BX
UT WOS:000446943500030
OA Bronze
DA 2022-11-30
ER

PT J
AU Zargarzadeh, M
   MadaahHosseini, HR
   Delavari, H
   Irajirad, R
   Aghaie, E
AF Zargarzadeh, Mehrzad
   MadaahHosseini, Hamid Reza
   Delavari, Hamid
   Irajirad, Rasoul
   Aghaie, Ermia
TI Synthesis of magnetite (Fe3O4)-Avastin nanocomposite as a potential drug
   for AMD treatment
SO MICRO & NANO LETTERS
LA English
DT Article
DE laser applications in medicine; nanomagnetics; magnetisation; molecular
   biophysics; biomedical materials; nanocomposites; drug delivery systems;
   nanofabrication; vision defects; cellular biophysics; drugs;
   nanomedicine; iron compounds; eye; precipitation (physical chemistry);
   nanoparticles; surgery; surgery; intravitreal injection; eye pressure;
   eye infections; body organs; lost vision; drug delivery technique;
   co-precipitation method; saturation magnetisation; synthesised iron
   oxide nanoparticles; systemic side effects; AMD treatment; macular
   degeneration; antivascular endothelial growth factor; magnetite-Avastin
   nanocomposite synthesis; age-related macular degeneration; blindness;
   laser therapy; blurring vision; flow cytometry; Fe3O4
ID INTRAVITREAL INJECTION; MACULAR DEGENERATION; COMPLICATIONS;
   PATHOGENESIS; BEVACIZUMAB
AB Age-related macular degeneration (AMD) is one of the prevailing causes of blindness in the aged over 50 years. There are several conventional treatments for AMD including laser therapy, surgery, and intravitreal injection of anti-vascular endothelial growth factor directly into the eye. Intravitreal injection may result in various side effects such as increasing the eye pressure, eye infections, blurring vision; furthermore, it can negatively affect other body organs. In addition, large number of injections would be required to regenerate the lost vision. To overcome some of these obstacles, the work proposes a new drug delivery technique by using Avastin-Fe3O4 nanocomposites synthesised through co-precipitation method with approximate size of 20 nm. The saturation magnetisation (M-s) of the synthesised iron oxide nanoparticles (NPs) was about 55.6648 emu/g which is completely suitable for movement of the (Avastin-Fe3O4) NPs. Besides, the results of the flow cytometry tests showed that 90.5% of NPs were Avastin loaded. The proposed new method can be replaced with conventional treatments as the long-term sustained release of Avastin instead of several injections as well as declining the systemic side effects due to the high concentration of Avastin in the posterior segment of the eye.
C1 [Zargarzadeh, Mehrzad] Sharif Univ Technol, Dept Mat Sci & Engn, Int Campus, Kish Isl 7941776655, Iran.
   [MadaahHosseini, Hamid Reza] Sharif Univ Technol, Dept Mat Sci & Engn, Tehran 1458889694, Iran.
   [Delavari, Hamid] Tarbiat Modares Univ, Dept Mat Engn, Tehran 14115143, Iran.
   [Irajirad, Rasoul] Imam Khomeini Hosp, Res Ctr Sci & Technol Med, Tehran 14197331411, Iran.
   [Aghaie, Ermia] Univ British Columbia Okanagan, Sch Engn, 3333 Univ Way, Kelowna, BC V1V 1V7, Canada.
C3 Sharif University of Technology; Sharif University of Technology;
   Tarbiat Modares University; University of British Columbia; University
   of British Columbia Okanagan
RP Zargarzadeh, M (通讯作者)，Sharif Univ Technol, Dept Mat Sci & Engn, Int Campus, Kish Isl 7941776655, Iran.
EM mehrzad.zargarzadeh@gmail.com
RI Aghaie, Ermia/X-3970-2019; Delavari H., Hamid/I-6021-2018
OI Aghaie, Ermia/0000-0003-4048-8250; Delavari H.,
   Hamid/0000-0003-0570-9767; Zargarzadeh, Mehrzad/0000-0002-4740-9538
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NR 19
TC 1
Z9 1
U1 1
U2 13
PU INST ENGINEERING TECHNOLOGY-IET
PI HERTFORD
PA MICHAEL FARADAY HOUSE SIX HILLS WAY STEVENAGE, HERTFORD SG1 2AY, ENGLAND
SN 1750-0443
J9 MICRO NANO LETT
JI Micro Nano Lett.
PD AUG
PY 2018
VL 13
IS 8
BP 1141
EP 1145
DI 10.1049/mnl.2017.0820
PG 5
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics; Materials Science
GA HC6NS
UT WOS:000451919100018
DA 2022-11-30
ER

PT J
AU Ivanov, IV
   Mappes, T
   Schaupp, P
   Lappe, C
   Wahl, S
AF Ivanov, Iliya V.
   Mappes, Timo
   Schaupp, Patrick
   Lappe, Christian
   Wahl, Siegfried
TI Ultraviolet radiation oxidative stress affects eye health
SO JOURNAL OF BIOPHOTONICS
LA English
DT Review
DE eye health; oxidative stress; ultraviolet radiation; UVA; UVB
ID MITOCHONDRIAL-DNA DAMAGE; AGE-RELATED MACULOPATHY; HYDROGEN-PEROXIDE;
   DECREASED EXPRESSION; ANTERIOR SEGMENT; EXPOSURE; EPITHELIUM; CATARACT;
   SPECTRUM; UVB
AB In the eye, ultraviolet radiation (UVR) is not known to contribute to visual perception but to mainly damage multiple structures. UVR carries higher energy than visible light and high dose exposure to UVR causes direct cellular damage, which has an important role in the development of cancer. This review provides an overview on the most recent knowledge on the role of UVR in oxidative stress (OS) in relation to noncancer ocular pathologies: various corneal pathologies, cataract, glaucoma and age-related macular degeneration. Possible OS signaling streams and mechanisms in the aging eye are discussed. Excessive exposure to UVR through live may seriously contribute to increase in OS of various eye tissues and thus lead to the advancement of serious ocular pathologies. Children are especially vulnerable to UVR because of their larger pupils and more transparent ocular media: up to 80% of a person's lifetime exposure to UVR is reached before the age of 18. Therefore, efficient everyday protection of the sensitive tissues of the eye by wearing of sunglasses, clear UVR-blocking spectacles or contact lenses should be considered from early age on. Many initiatives are taken worldwide to inform and raise the population's awareness about these possible UVR hazards to the eye.
C1 [Ivanov, Iliya V.; Wahl, Siegfried] Univ Tubingen, Inst Ophthalm Res, Tubingen, Germany.
   [Mappes, Timo; Schaupp, Patrick; Lappe, Christian; Wahl, Siegfried] Carl Zeiss Vis Int GmbH, Aalen, Germany.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University
   Hospital
RP Ivanov, IV (通讯作者)，Univ Tubingen, Inst Ophthalm Res, Tubingen, Germany.
EM iliya.ivanov@uni-tuebingen.de
RI Mappes, Timo MJ/A-6387-2010
FU University of Tuebingen [ZUK 63]
FX University of Tuebingen, Grant/Award Number: ZUK 63.
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NR 90
TC 67
Z9 70
U1 3
U2 28
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1864-063X
EI 1864-0648
J9 J BIOPHOTONICS
JI J. Biophotonics
PD JUL
PY 2018
VL 11
IS 7
AR e201700377
DI 10.1002/jbio.201700377
PG 13
WC Biochemical Research Methods; Biophysics; Optics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics; Optics
GA GM1NY
UT WOS:000437837000014
PM 29603665
OA hybrid
DA 2022-11-30
ER

PT J
AU Lin, P
AF Lin, Phoebe
TI The role of the intestinal microbiome in ocular inflammatory disease
SO CURRENT OPINION IN OPHTHALMOLOGY
LA English
DT Review
DE age-related macular degeneration; antibiotics; intestinal microbiome;
   short chain fatty acids; uveitis
ID GUT MICROBIOTA; MICE; PROTECTION; CELLS
AB Purpose of reviewThe intestinal commensal microbiota are important in shaping immune cell repertoire and are influenced by host genetics. Because of this intricate interaction, an intestinal dysbiosis has been associated with multiple immune-mediated polygenic diseases. This review summarizes the literature on how alterations in the intestinal microbiota contribute to immune-mediated ocular disease, and how to potentially target the gut microbiome for therapeutic benefit.Recent findingsSeveral groups have demonstrated the importance of the intestinal microbiome in uveitis pathogenesis. Two groups showed that altering the microbiota with oral antibiotics results in reduced uveitis severity, and another group demonstrated that a commensal bacterial antigen activates retina-specific autoreactive T cells, potentially indicating a commensal trigger for uveitis. We have found that commensal bacterial metabolites, short chain fatty acids, can suppress autoimmune uveitis. Age-related macular degeneration is associated with an intestinal dysbiosis, which can be influenced by genetic risk alleles and age-related eye disease study (AREDS) supplementation. Strategies that might be effective for targeting the intestinal microbiota might involve several approaches, including the use of antibiotics, drugs that supplement beneficial bacterial components or target inflammatory bacterial strains, dietary strategies or microbial transplantation.SummaryThe intestinal microbiota are potentially crucial in propagating inflammatory diseases of the eye, and can be targeted for therapeutic benefit.
C1 [Lin, Phoebe] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA.
C3 Oregon Health & Science University
RP Lin, P (通讯作者)，Oregon Hlth & Sci Univ, Casey Eye Inst, Ophthalmol, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA.
EM linp@ohsu.edu
FU National Eye Institute [K08 EY022948]; Collins Medical Trust Grant;
   Research to Prevent Blindness Career Development Award; National
   Institute of Health (Bethesda, Maryland, USA) [P30 EY010572]; Research
   to Prevent Blindness (New York, New York, USA)
FX This study was supported by a National Eye Institute Grant K08 EY022948,
   a Collins Medical Trust Grant, and a Research to Prevent Blindness
   Career Development Award (P.L.). This study was also supported by core
   grant P30 EY010572 from the National Institute of Health (Bethesda,
   Maryland, USA) and by unrestricted departmental funding from Research to
   Prevent Blindness (New York, New York, USA).
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NR 27
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Z9 35
U1 1
U2 29
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-8738
EI 1531-7021
J9 CURR OPIN OPHTHALMOL
JI Curr. Opin. Ophthalmol.
PD MAY
PY 2018
VL 29
IS 3
BP 261
EP 266
DI 10.1097/ICU.0000000000000465
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GC0AF
UT WOS:000429436700011
PM 29538183
DA 2022-11-30
ER

PT J
AU Keeling, E
   Lotery, AJ
   Tumbarello, DA
   Ratnayaka, JA
AF Keeling, Eloise
   Lotery, Andrew J.
   Tumbarello, David A.
   Ratnayaka, J. Arjuna
TI Impaired Cargo Clearance in the Retinal Pigment Epithelium (RPE)
   Underlies Irreversible Blinding Diseases
SO CELLS
LA English
DT Review
DE Retinal Pigment Epithelium (RPE); endosomes; phagosomes; lysosomes;
   autophagy; RPE cultures; Age-related Macular Degeneration (AMD)
ID PHOTORECEPTOR OUTER SEGMENTS; SPORADIC ALZHEIMERS-DISEASE; MACULAR
   DEGENERATION; ALPHA-SYNUCLEIN; LIPOFUSCIN ACCUMULATION; LYSOSOMAL
   BIOGENESIS; PHAGOSOME MATURATION; PRECURSOR PROTEIN; EARLY ENDOSOMES;
   SENILE PLAQUES
AB Chronic degeneration of the Retinal Pigment Epithelium (RPE) is a precursor to pathological changes in the outer retina. The RPE monolayer, which lies beneath the neuroretina, daily internalises and digests large volumes of spent photoreceptor outer segments. Impaired cargo handling and processing in the endocytic/phagosome and autophagy pathways lead to the accumulation of lipofuscin and pyridinium bis-retinoid A2E aggregates and chemically modified compounds such as malondialdehyde and 4-hydroxynonenal within RPE. These contribute to increased proteolytic and oxidative stress, resulting in irreversible damage to post-mitotic RPE cells and development of blinding conditions such as age-related macular degeneration, Stargardt disease and choroideremia. Here, we review how impaired cargo handling in the RPE results in their dysfunction, discuss new findings from our laboratory and consider how newly discovered roles for lysosomes and the autophagy pathway could provide insights into retinopathies. Studies of these dynamic, molecular events have also been spurred on by recent advances in optics and imaging technology. Mechanisms underpinning lysosomal impairment in other degenerative conditions including storage disorders, -synuclein pathologies and Alzheimer's disease are also discussed. Collectively, these findings help transcend conventional understanding of these intracellular compartments as simple waste disposal bags to bring about a paradigm shift in the way lysosomes are perceived.
C1 [Keeling, Eloise; Lotery, Andrew J.; Ratnayaka, J. Arjuna] Univ Southampton, Clin & Expt Sci, Fac Med, MP806,Tremona Rd, Southampton SO16 6YD, Hants, England.
   [Lotery, Andrew J.] Univ Hosp Southampton NHS Fdn Trust, Eye Unit, Southampton SO16 6YD, Hants, England.
   [Tumbarello, David A.] Univ Southampton, Biol Sci, Fac Nat & Environm Sci, Life Sci Bldg 85,Highfield Campus, Southampton SO17 1BJ, Hants, England.
C3 University of Southampton; University of Southampton; University
   Hospital Southampton NHS Foundation Trust; University of Southampton
RP Ratnayaka, JA (通讯作者)，Univ Southampton, Clin & Expt Sci, Fac Med, MP806,Tremona Rd, Southampton SO16 6YD, Hants, England.
EM E.Keeling@soton.acuk; A.J.Lotery@soton.ac.uk;
   D.A.Tumbarello@soton.ac.uk; J.Ratnayaka@soton.ac.uk
OI Lotery, Andrew/0000-0001-5541-4305; Tumbarello,
   David/0000-0002-5169-0561; Ratnayaka, J. Arjuna/0000-0002-1027-6938
FU Macular Society UK; National Centre for the Replacement, Refinement and
   Reduction of Animals in Research [NC/L001152/1]; RP Fighting Blindness
   [GR590]; National Eye Research Centre [SAC 020]; Fight for
   Sight/Alzheimer's Research UK [24AZ172]; Wellcome Trust Seed Award
   [205909/Z/17/Z]; National Institute for Health Research
   [NF-SI-0515-10020] Funding Source: researchfish; Fight for Sight
   [24AZ172] Funding Source: researchfish; National Centre for the
   Replacement [NC/L001152/1] Funding Source: researchfish
FX This work was supported by grants to JAR from the Macular Society UK,
   National Centre for the Replacement, Refinement and Reduction of Animals
   in Research (NC3R: #NC/L001152/1), RP Fighting Blindness (GR590),
   National Eye Research Centre (SAC 020), Fight for Sight/Alzheimer's
   Research UK (Ref: 24AZ172) and the Gift of Sight Appeal. AJL is a NIHR
   Senior Investigator. DAT is supported by a Wellcome Trust Seed Award
   (205909/Z/17/Z). We thank our colleagues Dr David A. Johnston and Dr
   David S. Chatelet at the Biomedical Imaging Centre (University of
   Southampton, UK) for expertise in confocal imaging and assistance with
   Amira software.
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NR 162
TC 32
Z9 33
U1 0
U2 11
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2073-4409
J9 CELLS-BASEL
JI Cells
PD FEB
PY 2018
VL 7
IS 2
AR 16
DI 10.3390/cells7020016
PG 19
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA FZ3US
UT WOS:000427516700007
PM 29473871
OA Green Accepted, Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Swinkels, M
   Zhang, JH
   Tilakaratna, V
   Black, G
   Perveen, R
   McHarg, S
   Inforzato, A
   Day, AJ
   Clark, SJ
AF Swinkels, Maurice
   Zhang, Justine H.
   Tilakaratna, Viranga
   Black, Graeme
   Perveen, Rahat
   McHarg, Selina
   Inforzato, Antonio
   Day, Anthony J.
   Clark, Simon J.
TI C-reactive protein and pentraxin-3 binding of factor H-like protein 1
   differs from complement factor H: implications for retinal inflammation
SO SCIENTIFIC REPORTS
LA English
DT Article
ID DISEASE-ASSOCIATED FORM; MACULAR DEGENERATION; BRUCHS MEMBRANE;
   EPITHELIAL-CELLS; STRUCTURAL BASIS; SIALIC-ACID; AGE; PTX3; ACTIVATION;
   RECOGNITION
AB Retinal inflammation plays a key role in the progression of age-related macular degeneration (AMD), a condition that leads to loss of central vision. The deposition of the acute phase pentraxin C-reactive protein (CRP) in the macula activates the complement system, thereby contributing to dysregulated inflammation. The complement protein factor H (FH) can bind CRP and down-regulate an inflammatory response. However, it is not known whether a truncated form of FH, called factor H-like protein 1 (FHL-1), which plays a significant regulatory role in the eye, also interacts with CRP. Here, we compare the binding properties of FHL-1 and FH to both CRP and the related protein pentraxin-3 (PTX3). We find that, unlike FH, FHL-1 can bind pro-inflammatory monomeric CRP (mCRP) as well as the circulating pentameric form. Furthermore, the four-amino acid C-terminal tail of FHL-1 (not present in FH) plays a role in mediating its binding to mCRP. PTX3 was found to be present in the macula of donor eyes and the AMD-associated Y402H polymorphism altered the binding of FHL-1 to PTX3. Our findings reveal that the binding characteristics of FHL-1 differ from those of FH, likely underpinning independent immune regulatory functions in the context of the human retina.
C1 [Swinkels, Maurice; Day, Anthony J.] Univ Manchester, Wellcome Trust Ctr Cell Matrix Res, Div Cell Matrix Biol & Regenerat Med,Sch Biol Sci, Fac Biol Med & Hlth,Manchester Acad Hlth Sci Ctr, Oxford Rd, Manchester M13 9PT, Lancs, England.
   [Zhang, Justine H.] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Royal Eye Hosp, Manchester Acad Hlth Sci Ctr, Manchester M13 9WL, Lancs, England.
   [Tilakaratna, Viranga; Black, Graeme; Perveen, Rahat; McHarg, Selina; Clark, Simon J.] Univ Manchester, Fac Biol Med & Hlth, Sch Biol Sci, Div Evolut & Genom Sci, Oxford Rd, Manchester M13 9PT, Lancs, England.
   [Black, Graeme; Perveen, Rahat] Cent Manchester Univ Hosp NHS Fdn Trust, St Marys Hosp, Manchester Ctr Genom Med, Manchester, Lancs, England.
   [Inforzato, Antonio] Humanitas Clin & Res Ctr, Via Manzoni 56, I-20089 Rozzano, Italy.
   [Inforzato, Antonio] Univ Milan, Dept Med Biotechnol & Translat Med, Via Vanvitelli 32, I-20129 Milan, Italy.
   [Swinkels, Maurice] Erasmus Univ, Med Ctr, Dept Hematol, S Gravendijkwal 230, NL-3015 CE Rotterdam, Netherlands.
C3 University of Manchester; Manchester Royal Eye Hospital; University of
   Manchester; University of Manchester; University of Manchester; IRCCS
   Humanitas Research Hospital; University of Milan; Erasmus University
   Rotterdam; Erasmus MC
RP Day, AJ (通讯作者)，Univ Manchester, Wellcome Trust Ctr Cell Matrix Res, Div Cell Matrix Biol & Regenerat Med,Sch Biol Sci, Fac Biol Med & Hlth,Manchester Acad Hlth Sci Ctr, Oxford Rd, Manchester M13 9PT, Lancs, England.; Clark, SJ (通讯作者)，Univ Manchester, Fac Biol Med & Hlth, Sch Biol Sci, Div Evolut & Genom Sci, Oxford Rd, Manchester M13 9PT, Lancs, England.
EM anthony.day@manchester.ac.uk; simon.clark-3@manchester.ac.uk
RI Inforzato, Antonio/ABG-4513-2020; Zhang, Justine/AAK-8314-2020; Day,
   Anthony/O-1658-2015; Black, Graeme/K-7374-2015
OI Inforzato, Antonio/0000-0001-8110-0027; Zhang,
   Justine/0000-0001-8385-2003; Clark, Simon/0000-0001-8394-8355; Day,
   Anthony/0000-0002-1415-3134; Black, Graeme/0000-0001-8727-6592
FU Medical Research Council [MR/K024418/1]; Fight for Sight UK [1517/1518];
   Macular Society UK [12928]; MRC [MR/K024418/1] Funding Source: UKRI;
   National Institute for Health Research [ACF-2015-06-009] Funding Source:
   researchfish; Fight for Sight [1517/18] Funding Source: researchfish
FX This work was funded by the Medical Research Council (MR/K024418/1);
   Fight for Sight UK (1517/1518) and the Macular Society UK (12928).
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NR 67
TC 21
Z9 21
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JAN 26
PY 2018
VL 8
AR 1643
DI 10.1038/s41598-017-18395-7
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA FT8TO
UT WOS:000423426300026
PM 29374201
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU O'Connell, C
   Mahboobin, A
   Drexler, S
   Redfern, MS
   Perera, S
   Nau, AC
   Cham, R
AF O'Connell, Caitlin
   Mahboobin, Arash
   Drexler, Scott
   Redfern, Mark S.
   Perera, Subashan
   Nau, Amy C.
   Cham, Rakie
TI Effects of acute peripheral/central visual field loss on standing
   balance
SO EXPERIMENTAL BRAIN RESEARCH
LA English
DT Article
DE Balance; Vision; Sensory integration; Posturography
ID HUMAN POSTURAL CONTROL; SENSORY REWEIGHTING DYNAMICS; COMMUNITY-DWELLING
   WOMEN; SALISBURY EYE EVALUATION; VOXEL-BASED MORPHOMETRY; AGE-RELATED
   MACULOPATHY; OPEN-ANGLE GLAUCOMA; MINI-MENTAL-STATE; MACULAR
   DEGENERATION; MOBILITY PERFORMANCE
AB Vision impairments such as age-related macular degeneration (AMD) and glaucoma are among the top risk factors for geriatric falls and falls-related injuries. AMD and glaucoma lead to loss of the central and peripheral visual fields, respectively. This study utilized a custom contact lens model to occlude the peripheral or central visual fields in healthy adults, offering a novel within-subject approach to improve our understanding of the etiology of balance impairments that may lead to an increased fall risk in patients with visual field loss. Two dynamic posturography tests, including an adapted version of the Sensory Organization Test and a virtual reality environment with the visual scene moving sinusoidally, were used to evaluate standing balance. Balance stability was quantified by displacement and time-normalized path length of the center of pressure. Nine young and eleven older healthy adults wore visual field occluding contact lenses during posturography assessments to compare the effects of acute central and peripheral visual field occlusion. The results found that visual field occlusion had greater impact on older adults than young adults, specifically when proprioceptive cues are unreliable. Furthermore, the results suggest that both central and peripheral visions are important in postural control; however, peripheral vision may be more sensitive to movement in the environment.
C1 [O'Connell, Caitlin; Mahboobin, Arash; Redfern, Mark S.; Cham, Rakie] Univ Pittsburgh, Dept Bioengn, 439 Benedum Hall,3700 OHara St, Pittsburgh, PA 15261 USA.
   [Drexler, Scott] Univ Pittsburgh, Dept Ophthalmol, UPMC Eye Ctr, 203 Lothrop St, Pittsburgh, PA 15213 USA.
   [Perera, Subashan] Univ Pittsburgh, Div Geriatr Med, 3471 Fifth Ave, Pittsburgh, PA 15213 USA.
   [Perera, Subashan] Univ Pittsburgh, Dept Biostat, 130 De Soto St, Pittsburgh, PA 15261 USA.
   [Nau, Amy C.] Korb Res, 400 Commonwealth Ave,Unit 2, Boston, MA 02215 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); University
   of Pittsburgh; Pennsylvania Commonwealth System of Higher Education
   (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of
   Higher Education (PCSHE); University of Pittsburgh; Pennsylvania
   Commonwealth System of Higher Education (PCSHE); University of
   Pittsburgh
RP O'Connell, C (通讯作者)，Univ Pittsburgh, Dept Bioengn, 439 Benedum Hall,3700 OHara St, Pittsburgh, PA 15261 USA.
EM caitlino@pitt.edu
RI Perera, Subashan/D-7603-2014
FU National Institutes on Aging [R03 AG04374]; NATIONAL INSTITUTE ON AGING
   [R03AG043748] Funding Source: NIH RePORTER
FX Funding provided by the National Institutes on Aging [R03 AG04374]. We
   would like to thank Dr. Joseph Furman and his team for screening
   participants with balance disorders.
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NR 67
TC 11
Z9 12
U1 4
U2 34
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0014-4819
EI 1432-1106
J9 EXP BRAIN RES
JI Exp. Brain Res.
PD NOV
PY 2017
VL 235
IS 11
BP 3261
EP 3270
DI 10.1007/s00221-017-5045-x
PG 10
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Neurosciences & Neurology
GA FK4EE
UT WOS:000413441500003
PM 28765993
DA 2022-11-30
ER

PT J
AU Rajapakse, D
   Curtis, T
   Chen, M
   Xu, HP
AF Rajapakse, Dinusha
   Curtis, Tim
   Chen, Mei
   Xu, Heping
TI Zinc Protects Oxidative Stress-Induced RPE Death by Reducing
   Mitochondrial Damage and Preventing Lysosome Rupture
SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; OUTER SEGMENTS;
   FACTOR-H; AGE; AUTOPHAGY; CELLS; SUSCEPTIBILITY; DEGRADATION; COPPER
AB Zinc deficiency is known to increase the risk of the development of age-related macular degeneration (AMD), although the underlying mechanism remains poorly defined. In this study, we investigated the effect of zinc on retinal pigment epithelium (RPE) survival and function under oxidative conditions. Zinc level was 5.4 mu M in normal culture conditions (DMEM/F12 with 10% FCS) and 1.5 mu M in serum-free medium (DMEM/F12). Under serum-free culture conditions, the treatment of RPE cells with oxidized photoreceptor outer segment (oxPOS) significantly increased intracellular ROS production, reduced ATP production, and promoted RPE death compared to oxPOS-treated RPE under normal culture condition. Serum deprivation also reduced RPE phagocytosis of oxPOS and exacerbated oxidative insult-induced cathepsin B release from lysosome, an indicator of lysosome rupture. The addition of zinc in the serum-free culture system dose dependently reduced ROS production, recovered ATP production, and reduced oxidative stress-(oxPOS- or 4-HNE) induced cell death. Zinc supplementation also reduced oxidative stress-mediated cathepsin B release in RPE cells. Our results suggest that zinc deficiency sensitizes RPE cells to oxidative damage, and zinc supplementation protects RPE cells from oxidative stress-induced death by improving mitochondrial function and preventing lysosome rupture.
C1 [Rajapakse, Dinusha; Curtis, Tim; Chen, Mei; Xu, Heping] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Ctr Med Expt, 97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland.
C3 Queens University Belfast
RP Xu, HP (通讯作者)，Queens Univ Belfast, Sch Med Dent & Biomed Sci, Ctr Med Expt, 97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland.
EM heping.xu@qub.ac.uk
RI Xu, Heping/A-4430-2008; Curtis, Tim/AEU-9750-2022
OI Xu, Heping/0000-0003-4000-931X; Curtis, Tim/0000-0003-1543-2781;
   Rajapakse, Dinusha/0000-0002-5210-6494
FU Queen's University Belfast International Postgraduate Training programme
FX The study was funded by the Queen's University Belfast International
   Postgraduate Training programme.
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NR 46
TC 23
Z9 24
U1 2
U2 14
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 2017
VL 2017
AR 6926485
DI 10.1155/2017/6926485
PG 12
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA FM5EE
UT WOS:000415052800001
PM 29348791
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Tu, G
   Zhang, YF
   Wei, W
   Li, LG
   Zhang, YM
   Yang, J
   Xing, YQ
AF Tu, Gerile
   Zhang, Yu-Feng
   Wei, Wei
   Li, Langen
   Zhang, Yanmei
   Yang, Jia
   Xing, Yiqiao
TI Allicin attenuates H2O2-induced cytotoxicity in retinal pigmented
   epithelial cells by regulating the levels of reactive oxygen species
SO MOLECULAR MEDICINE REPORTS
LA English
DT Article
DE garlic; retinal pigmented epithelial cells; age-related macular
   degeneration; oxidative stress
ID OXIDATIVE STRESS; ACTIVATION; NRF2; LOCALIZATION; INJURY
AB Retinal pigmented epithelial cell (RPE) oxidative stress is known to have a vital role in the etiology of age-related macular degeneration (AMD). The present study aimed to investigate whether allicin, a natural product with antioxidant activity, was able to protect RPEs (ARPE-19) from hydrogen peroxide (H2O2)-induced damage, and to determine the underlying mechanisms. The 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was used to determine cellular viability, and reactive oxygen species (ROS) were detected using a ROS Assay kit. The results demonstrated that allicin was able to protect ARPE-19 cells from H2O2-induced damage in a dose-dependent manner. In addition, allicin attenuated oxidative stress by reducing the levels of intracellular ROS and malondialdehyde (MDA), and enhancing the glutathione/glutathione disulfide (GSSG) ratio. With regards to the underlying mechanism, allicin was able to markedly modulate the expression levels of ROS-associated enzymes, including superoxide dismutase, NADPH oxidase 4 and NAD(P)H dehydrogenase quinone 1, and elevate the activity of nuclear factor erythroid 2-related factor 2 in the H2O2-stimulated ARPE-19 cells. These results suggested that allicin may exert protective effects against H2O2-induced cyto-toxicity in RPEs via ROS regulation.
C1 [Tu, Gerile; Zhang, Yu-Feng; Li, Langen; Xing, Yiqiao] Wuhan Univ, Remnin Hosp, Dept Ophthalmol, 99 Zhang Zhidong Rd, Wuhan 430060, Hubei, Peoples R China.
   [Wei, Wei] Inner Mongolia Peoples Hosp, Dept Ophthalmol, Hohhot 010017, Inner Mongolia, Peoples R China.
   [Zhang, Yanmei] Inner Mongolia Peoples Hosp, Dept Neurol, Hohhot 010017, Inner Mongolia, Peoples R China.
   [Yang, Jia] Inner Mongolia Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Hohhot 010059, Inner Mongolia, Peoples R China.
C3 Wuhan University; Inner Mongolia Medical University
RP Xing, YQ (通讯作者)，Wuhan Univ, Remnin Hosp, Dept Ophthalmol, 99 Zhang Zhidong Rd, Wuhan 430060, Hubei, Peoples R China.
EM yqxingwh@sohu.com
RI Zhang, Yufeng/GZL-1973-2022
FU Renmin Hospital of Wuhan University [RHWU-13-2012]; Inner Mongolia
   People's Hospital [2012-16-02]
FX The present study was supported by the Renmin Hospital of Wuhan
   University (grant no. RHWU-13-2012) and Inner Mongolia People's Hospital
   (grant no. 2012-16-02).
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NR 40
TC 25
Z9 26
U1 2
U2 17
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1791-2997
EI 1791-3004
J9 MOL MED REP
JI Mol. Med. Rep.
PD MAR
PY 2016
VL 13
IS 3
BP 2320
EP 2326
DI 10.3892/mmr.2016.4797
PG 7
WC Oncology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Research & Experimental Medicine
GA DF8TS
UT WOS:000371633000052
PM 26781848
OA Bronze
DA 2022-11-30
ER

PT J
AU Yasuma, R
   Cicatiello, V
   Mizutani, T
   Tudisco, L
   Kim, Y
   Tarallo, V
   Bogdanovich, S
   Hirano, Y
   Kerur, N
   Li, SJ
   Yasuma, T
   Fowler, BJ
   Wright, CB
   Apicella, I
   Greco, A
   Brunetti, A
   Ambati, BK
   Helmers, SB
   Lundberg, IE
   Viklicky, O
   Leusen, JHW
   Verbeek, JS
   Gelfand, BD
   Bastos-Carvalho, A
   De Falco, S
   Ambati, J
AF Yasuma, Reo
   Cicatiello, Valeria
   Mizutani, Takeshi
   Tudisco, Laura
   Kim, Younghee
   Tarallo, Valeria
   Bogdanovich, Sasha
   Hirano, Yoshio
   Kerur, Nagaraj
   Li, Shengjian
   Yasuma, Tetsuhiro
   Fowler, Benjamin J.
   Wright, Charles B.
   Apicella, Ivana
   Greco, Adelaide
   Brunetti, Arturo
   Ambati, Balamurali K.
   Helmers, Sevim Barbasso
   Lundberg, Ingrid E.
   Viklicky, Ondrej
   Leusen, Jeanette H. W.
   Verbeek, J. Sjef
   Gelfand, Bradley D.
   Bastos-Carvalho, Ana
   De Falco, Sandro
   Ambati, Jayakrishna
TI Intravenous immune globulin suppresses angiogenesis in mice and humans
SO SIGNAL TRANSDUCTION AND TARGETED THERAPY
LA English
DT Article
ID FC-GAMMA RECEPTORS; MOUSE MODEL; IMMUNOGLOBULIN; IVIG; INHIBITION;
   TARGET; TISSUE; CELLS
AB Human intravenous immune globulin (IVIg), a purified IgG fraction composed of similar to 60% IgG1 and obtained from the pooled plasma of thousands of donors, is clinically used for a wide range of diseases. The biological actions of IVIg are incompletely understood and have been attributed both to the polyclonal antibodies therein and also to their IgG (IgG) Fc regions. Recently, we demonstrated that multiple therapeutic human IgG1 antibodies suppress angiogenesis in a target-independent manner via FcyRI, a high-affinity receptor for IgG1. Here we show that IVIg possesses similar anti-angiogenic activity and inhibited blood vessel growth in five different mouse models of prevalent human diseases, namely, neovascular age-related macular degeneration, corneal neovascularization, colorectal cancer, fibrosarcoma and peripheral arterial ischemic disease. Angioinhibition was mediated by the Fc region of IVIg, required FcyRl and had similar potency in transgenic mice expressing human FcyRs. Finally, IVIg therapy administered to humans for the treatment of inflammatory or autoimmune diseases reduced kidney and muscle blood vessel densities. These data place IVIg, an agent approved by the US Food and Drug Administration, as a novel angioinhibitory drug in doses that are currently administered in the clinical setting. In addition, they raise the possibility of an unintended effect of IVIg on blood vessels.
C1 [Yasuma, Reo; Mizutani, Takeshi; Kim, Younghee; Tarallo, Valeria; Bogdanovich, Sasha; Hirano, Yoshio; Kerur, Nagaraj; Li, Shengjian; Yasuma, Tetsuhiro; Fowler, Benjamin J.; Wright, Charles B.; Gelfand, Bradley D.; Bastos-Carvalho, Ana; Ambati, Jayakrishna] Univ Kentucky, Dept Ophthalmol & Visual Sci, Lexington, KY 40506 USA.
   [Yasuma, Reo] Nagoya Univ, Dept Ophthalmol, Grad Sch Med, Nagoya, Aichi, Japan.
   [Cicatiello, Valeria; Tudisco, Laura; Tarallo, Valeria; Apicella, Ivana; De Falco, Sandro] CNR, Angiogenesis Lab, Inst Genet & Biophys, Naples, Italy.
   [Cicatiello, Valeria] Bio Ker, MultiMed Grp, Naples, Italy.
   [Fowler, Benjamin J.; Ambati, Jayakrishna] Univ Kentucky, Dept Physiol, Lexington, KY 40506 USA.
   [Greco, Adelaide; Brunetti, Arturo] Univ Naples Federico II, Dept Adv Biomed Sci, Naples, Italy.
   [Greco, Adelaide; Brunetti, Arturo] CEINGE Biotecnol Avanzate Sc Srl, Naples, Italy.
   [Ambati, Balamurali K.] Univ Utah, Sch Med, Dept Ophthalmol & Visual Sci, Moran Eye Ctr, Salt Lake City, UT USA.
   [Ambati, Balamurali K.] Vet Affairs Salt Lake City Healthcare Syst, Dept Ophthalmol, Salt Lake City, UT USA.
   [Helmers, Sevim Barbasso; Lundberg, Ingrid E.] Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
   [Viklicky, Ondrej] Inst Clin & Expt Med, Dept Nephrol, Prague 4, Czech Republic.
   [Leusen, Jeanette H. W.] Univ Med Ctr Utrecht, Immunotherapy Lab, Lab Translat Immunol, Utrecht, Netherlands.
   [Verbeek, J. Sjef] Leiden Univ, Dept Human Genet, Med Ctr, Leiden, Netherlands.
   [Gelfand, Bradley D.] Univ Kentucky, Dept Biomed Engn, Lexington, KY USA.
   [Gelfand, Bradley D.] Univ Kentucky, Dept Microbiol Immunol & Mol Genet, Lexington, KY USA.
   [De Falco, Sandro] IRCCS MultiMed, Milan, Italy.
C3 University of Kentucky; Nagoya University; Consiglio Nazionale delle
   Ricerche (CNR); Istituto di Genetica e Biofisica "Adriano
   Buzzati-Traverso" (IGB-CNR); University of Kentucky; University of
   Naples Federico II; Utah System of Higher Education; University of Utah;
   US Department of Veterans Affairs; Karolinska Institutet; Karolinska
   University Hospital; Institute for Clinical & Experimental Medicine
   (IKEM); Utrecht University; Utrecht University Medical Center; Leiden
   University; Leiden University Medical Center (LUMC); Leiden University -
   Excl LUMC; University of Kentucky; University of Kentucky; IRCCS
   Multimedica
RP Ambati, J (通讯作者)，Univ Kentucky, Dept Ophthalmol & Visual Sci, Lexington, KY 40506 USA.; De Falco, S (通讯作者)，CNR, Angiogenesis Lab, Inst Genet & Biophys, Naples, Italy.; Ambati, J (通讯作者)，Univ Kentucky, Dept Physiol, Lexington, KY 40506 USA.; De Falco, S (通讯作者)，IRCCS MultiMed, Milan, Italy.
EM jamba2@email.uky.edu; sandro.defako@igb.cnr.it
RI Brunetti, Arturo/AAE-5261-2019; , Jeanette/AAG-3736-2019; Greco,
   Adelaide/C-7679-2018
OI Brunetti, Arturo/0000-0001-7057-3494; Greco,
   Adelaide/0000-0001-6841-1963; Hirano, Yoshio/0000-0002-9173-0839; De
   Falco, Sandro/0000-0002-6501-1697; Viklicky, Ondrej/0000-0003-1049-2195;
   Tarallo, Valeria/0000-0002-6920-4402; Leusen,
   Jeanette/0000-0003-4982-6914
FU US National Institutes of Health (NIH) [DP1GM114862, R01EY018350,
   R01EY018836, R01EY020672, R01EY022238, R01EY024068]; Doris Duke
   Distinguished Clinical Scientist Award; Burroughs Wellcome Fund Clinical
   Scientist Award in Translational Research; Ellison Medical Foundation
   Senior Scholar in Aging Award; Foundation Fighting Blindness Individual
   Investigator Research Award; Harrington Discovery Institute
   Scholar-Innovator Award; Carl Marshall Reeves Foundation; John Templeton
   Foundation; Dr E Vernon Smith and Eloise C Smith Macular Degeneration
   Endowed Chair; Research to Prevent Blindness; AIRC (Associazione
   Italiana Ricerca sul Cancro) [IG11420]; Italian Ministry for Scientific
   Research [PON01_01434]; NIH [T32HL091812, UL1RR033173, K99/R00EY024336,
   R01EY017182, R01EY017950]; Alcon Research Award; Programme for Advanced
   Medical Education - Fundacao Calouste Gulbenkian, Portugal; Programme
   for Advanced Medical Education - Fundacao Champalimaud, Portugal;
   Programme for Advanced Medical Education - Ministerio da Saude,
   Portugal; Programme for Advanced Medical Education - Fundacao para a
   Ciencia e Tecnologia, Portugal; Bayer Global Ophthalmology Research
   Award; Alcon Japan Research award; Beckman Initiative for Macular
   Research; International Retinal Research Foundation; American Heart
   Association; VA Merit Award; Department of Defense; Ministry of Health,
   Czech Republic-conceptual development of research organization
   (Institute for Clinical and Experimental Medicine-IKEM) [IN 00023001];
   NATIONAL EYE INSTITUTE [R00EY024336] Funding Source: NIH RePORTER
FX We thank TS Khurana, S Bondada, K Ambati, AM Rao and GS Rao for
   discussions; L Toll, GR Pattison R King, L Xu, M McConnell, C Payne, D
   Robertson, G Botzet, A Uiettenbogaard, E Lindroos and the Institute of
   Genetics and Biophysics animal house and integrated microscopy
   facilities for technical assistance. JA was supported by US National
   Institutes of Health (NIH) grants DP1GM114862, R01EY018350, R01EY018836,
   R01EY020672, R01EY022238 and R01EY024068, Doris Duke Distinguished
   Clinical Scientist Award, Burroughs Wellcome Fund Clinical Scientist
   Award in Translational Research, Ellison Medical Foundation Senior
   Scholar in Aging Award, Foundation Fighting Blindness Individual
   Investigator Research Award, Harrington Discovery Institute
   Scholar-Innovator Award, Carl Marshall Reeves Foundation, John Templeton
   Foundation, Dr E Vernon Smith and Eloise C Smith Macular Degeneration
   Endowed Chair, and Research to Prevent Blindness departmental
   unrestricted grant; SDeF by AIRC (Associazione Italiana Ricerca sul
   Cancro) grant IG11420 and Italian Ministry for Scientific Research,
   project PON01_01434; BJF and SB by NIH T32HL091812 and UL1RR033173; YH
   by Alcon Research Award; AB-C by the Programme for Advanced Medical
   Education (sponsored by Fundacao Calouste Gulbenkian, Fundacao
   Champalimaud, Ministerio da Saude and Fundacao para a Ciencia e
   Tecnologia, Portugal) and Bayer Global Ophthalmology Research Award; YH
   by Alcon Japan Research award; NK by Beckman Initiative for Macular
   Research and NIH K99/R00EY024336; CBW by International Retinal Research
   Foundation; BDG by American Heart Association and International Retinal
   Research Foundation; BKA by NIH R01EY017182 and R01EY017950, VA Merit
   Award and Department of Defense; and OV by Ministry of Health, Czech
   Republic-conceptual development of research organization (Institute for
   Clinical and Experimental Medicine-IKEM, IN 00023001).
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NR 40
TC 19
Z9 21
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2095-9907
EI 2059-3635
J9 SIGNAL TRANSDUCT TAR
JI Signal Transduct. Target. Ther.
PY 2016
VL 1
AR 15002
DI 10.1038/sigtrans.2015.2
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA VH7TQ
UT WOS:000454602900002
PM 26925256
OA Green Published, gold, Green Accepted
DA 2022-11-30
ER

PT J
AU Thackaberry, EA
   Farman, C
   Bantseev, V
   Schuetz, C
   Baker, JF
   Brown, MH
   Learn, DB
AF Thackaberry, Evan A.
   Farman, Cynthia
   Bantseev, Vladimir
   Schuetz, Chris
   Baker, Julia F.
   Brown, Michael H.
   Learn, Douglas B.
TI Intravitreal administration of known phototoxicants in the rabbit fails
   to produce phototoxicity: implications for phototoxicity testing of
   intravitreally administered small molecule therapeutics
SO CUTANEOUS AND OCULAR TOXICOLOGY
LA English
DT Article
DE Doxycycline; drug safety; intravitreal administration; lomefloxacin;
   8-methoxypsoralen; phototoxicity; safety assessment; stannsoporfrin
ID EYE; PHARMACOKINETICS; FORMULATIONS; DOXYCYCLINE; KINETICS
AB Context: Intravitreal (ITV) dosing has become a clinically important route of administration for the treatment of uveitis, endophthalmitis, retinal vein occlusion, diabetic macular edema and age-related macular degeneration. Despite this, there are no validated non-clinical models of phototoxicity for ITV products.
   Objective: The objective of this study was to develop an ITV rabbit model of phototoxicity for use in assessing the photosafety of small molecules therapeutics.
   Materials and methods: Dutch Belted rabbits were intravitreally injected bilaterally with four known phototoxicants: 8-methoxypsoralen, lomefloxacin, doxycycline and stannsoporfrin. Triescence(R), a non-phototoxic triamcinolone acetonide steroid formulation designed for ITV administration, was used as a negative control. One eye was then irradiated with solar-simulated ultraviolet radiation for 30 min, 1 h after dosing, while the other eye was occluded, serving as a non-irradiated control.
   Results: Despite the direct administration of known phototoxicants into the vitreous, no evidence of ocular phototoxicity was observed in any dose group. Direct (non-phototoxic) retinal toxicity was observed in the doxycycline dose group only.
   Conclusion: These data suggest that the posterior segment of the rabbit eye is protected against phototoxicity by anatomical and/or physiological mechanisms, and is not a useful model for the assessment of phototoxicity of intravitreally administered molecules.
C1 [Thackaberry, Evan A.; Farman, Cynthia; Bantseev, Vladimir; Schuetz, Chris] Genentech Inc, Dept Safety Assessment, 1 DNA Way, San Francisco, CA 94080 USA.
   [Baker, Julia F.] Charles River Pathol Associates, Frederick, MD USA.
   [Brown, Michael H.] Anim Eye Ctr New Jersey, Little Falls, NJ USA.
   [Learn, Douglas B.] Charles River Labs, Horsham, PA USA.
C3 Roche Holding; Genentech
RP Thackaberry, EA (通讯作者)，Genentech Inc, Dept Safety Assessment, 1 DNA Way, San Francisco, CA 94080 USA.
EM thackabe@gene.com
OI Thackaberry, Evan/0000-0001-7161-6361
CR Aydin E., 2007, Arch Soc Esp Oftalmol, V82, P223
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NR 35
TC 3
Z9 3
U1 1
U2 3
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 2015
VL 34
IS 4
BP 265
EP 270
DI 10.3109/15569527.2014.961070
PG 6
WC Ophthalmology; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Toxicology
GA DF5MD
UT WOS:000371395000001
PM 25373486
DA 2022-11-30
ER

PT J
AU Kang-Mieler, JJ
   Osswald, CR
   Mieler, WF
AF Kang-Mieler, Jennifer J.
   Osswald, Christian R.
   Mieler, William F.
TI Advances in ocular drug delivery: emphasis on the posterior segment
SO EXPERT OPINION ON DRUG DELIVERY
LA English
DT Review
DE anterior segment delivery; drug delivery; eye; posterior segment
   delivery
ID INTRAVITREAL AFLIBERCEPT INJECTION; DEXAMETHASONE PHOSPHATE;
   FLUOCINOLONE ACETONIDE; PHOTODYNAMIC THERAPY; MACULAR EDEMA; EYE DROPS;
   PHASE-I; IONTOPHORESIS; DEGENERATION; IMPLANT
AB Introduction: Recent advances in pharmacological therapies to treat ocular diseases such as glaucoma, age-related macular degeneration, diabetic macular edema and retinal vascular occlusions have greatly improved the prognosis for these diseases. Due to these advances in pharmacological therapy, there is a great deal of interest in minimally invasive delivery methods, which has generated rapid developments in the field of ocular drug delivery.
   Areas covered: This review will summarize currently available and recent developments for ocular drug delivery to both the anterior and posterior segments. Modes of delivery, including topical, systemic, transcleral/periocular and intravitreal, will be discussed and corresponding examples will be given. This review will highlight the advantages and disadvantages of each mode of delivery and discuss strategies to address these issues.
   Expert opinion: An ideal therapy should maintain effective levels of drug for the intended duration of treatment following a single application, yet a significant number of months of therapy may be required. There are numerous approaches under investigation to improve treatment options. From the use of novel biomaterial implants and depots for sustained release, to prodrug formations, to iontophoresis to improve drug delivery, the main emphasis will continue to be placed on less invasive, longer acting, sustained release formulations in the treatment of numerous ocular disorders.
C1 [Kang-Mieler, Jennifer J.; Osswald, Christian R.] IIT, Dept Biomed Engn, Chicago, IL 60616 USA.
   [Mieler, William F.] Univ Illinois, Illinois Eye & Ear Infirm, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA.
C3 Illinois Institute of Technology; University of Illinois System;
   University of Illinois Chicago; University of Illinois Chicago Hospital
RP Kang-Mieler, JJ (通讯作者)，IIT, Dept Biomed Engn, Chicago, IL 60616 USA.
EM kang-mieler@iit.edu
OI Kang-Mieler, Jennifer/0000-0002-2844-5066
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NR 85
TC 89
Z9 93
U1 0
U2 65
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1742-5247
EI 1744-7593
J9 EXPERT OPIN DRUG DEL
JI Expert Opin. Drug Deliv.
PD OCT
PY 2014
VL 11
IS 10
BP 1647
EP 1660
DI 10.1517/17425247.2014.935338
PG 14
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA AP8VZ
UT WOS:000342358700012
PM 24975820
DA 2022-11-30
ER

PT J
AU Cruz-Gonzalez, F
   Cieza-Borrella, C
   Cabrillo-Estevez, L
   Canete-Campos, C
   Escudero-Dominguez, F
   Gonzalez-Sarmiento, R
AF Cruz-Gonzalez, Fernando
   Cieza-Borrella, Clara
   Cabrillo-Estevez, L.
   Canete-Campos, Cristina
   Escudero-Dominguez, Francisco
   Gonzalez-Sarmiento, Rogelio
TI VEGF A (rs699947 and rs833061) and VEGFR2 (rs2071559) Gene Polymorphisms
   are not Associated with AMD Susceptibility in a Spanish Population
SO CURRENT EYE RESEARCH
LA English
DT Article
DE AMD; Angiogenesis; degeneration; genetics; macula
ID ENDOTHELIAL GROWTH-FACTOR; COMPLEMENT FACTOR-H; MACULAR DEGENERATION;
   RISK; DISEASE
AB Purpose: Age-related macular degeneration (AMD) is a multifactorial disease due to interaction between genetic and environmental factors. Increased angiogenesis plays a central role in AMD development. Previous studies on the potential link between AMD and vascular endothelial growth factor (VEGFA) and vascular endothelial growth factor receptor (VEGFR) have yielded conflicting results. We have analysed if polymorphisms in genes coding for VEGFA and VEGFR are associated to susceptibility to suffer AMD in a cohort of Spanish subjects.
   Patients and Methods: We obtained peripheral blood samples from 151 patients with diagnosis of exudative AMD. We also studied 91 healthy subjects matched by age. We studied VEGFA rs699947 and rs833061, and VEGFR2 rs2071559 polymorphisms using real-time PCR with TaqMan probes.
   Results: We did not find statistically significant differences in genotypic distribution of VEGF rs699947 and rs833061 polymorphisms between patients and controls. However, analysis of VEGFR2 rs2071559 polymorphism shows that carriers of GG genotype are more frequent in subjects with AMD (p: 0.032; Odds Ratio(OR): 1.933; confidence interval (CI): 1.053-3.549), but, when corrected by Bonferroni testing, the result was found to be not significant.
   Conclusion: Our study shows that VEGFA rs699947 and rs833061 and VEGFR2 rs2071559 polymorphisms do not modify the risk of suffering AMD in a Spanish population.
C1 [Cruz-Gonzalez, Fernando; Cabrillo-Estevez, L.; Canete-Campos, Cristina; Escudero-Dominguez, Francisco] Hosp Univ Salamanca, Dept Oftalmol, Salamanca 37007, Spain.
   [Cieza-Borrella, Clara; Gonzalez-Sarmiento, Rogelio] Univ Salamanca, CSIC, Unidad Medicina Mol, Dept Med, E-37008 Salamanca, Spain.
   [Cieza-Borrella, Clara; Gonzalez-Sarmiento, Rogelio] Univ Salamanca, IBMCC, CSIC, E-37008 Salamanca, Spain.
   [Cruz-Gonzalez, Fernando; Cieza-Borrella, Clara; Gonzalez-Sarmiento, Rogelio] Hosp Univ Salamanca, IBSAL, Salamanca 37007, Spain.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); University of
   Salamanca; Consejo Superior de Investigaciones Cientificas (CSIC);
   CSIC-USAL - Instituto de Biologia Molecular y Celular del Cancer de
   Salamanca (IBMCC); University of Salamanca
RP Cruz-Gonzalez, F (通讯作者)，Hosp Univ Salamanca, Serv Oftalmol, Paseo San Vicente 182, Salamanca 37007, Spain.
EM cruzgonzalez.fernando@gmail.com
RI Gonzalez-Sarmiento, Rogelio/V-5526-2019
OI Gonzalez-Sarmiento, Rogelio/0000-0002-2726-6795; Cieza-Borrella,
   Clara/0000-0003-2739-1040
FU Junta de Castilla y Leon [GRS215/A/08, FIS PI10/00219]
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 that have no non-financial interests
   that may be relevant to the submitted work. RG-S is supported by Grants
   from Junta de Castilla y Leon GRS215/A/08 and FIS PI10/00219.
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NR 28
TC 4
Z9 4
U1 0
U2 3
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0271-3683
EI 1460-2202
J9 CURR EYE RES
JI Curr. Eye Res.
PD DEC
PY 2013
VL 38
IS 12
BP 1274
EP 1277
DI 10.3109/02713683.2013.819926
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 237FK
UT WOS:000325853800013
PM 23971975
DA 2022-11-30
ER

PT J
AU Lamoke, F
   Ripandelli, G
   Webster, S
   Montemari, A
   Maraschi, A
   Martin, P
   Marcus, DM
   Liou, GI
   Bartoli, M
AF Lamoke, Folami
   Ripandelli, Guido
   Webster, Scott
   Montemari, AnnaLisa
   Maraschi, AnnaMaria
   Martin, Pamela
   Marcus, Dennis M.
   Liou, Gregory I.
   Bartoli, Manuela
TI Loss of thioredoxin function in retinas of mice overexpressing amyloid
   beta
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Thioredoxin; Oxidative stress; Antioxidants; Apoptosis signaling
   kinase-1; p38 mitogen-activated protein kinase; Amyloid beta; Retinal
   degeneration; Free radicals
ID ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; OXIDATIVE STRESS; GANGLION-CELLS;
   MAMMALIAN THIOREDOXIN; MACULAR DEGENERATION; MOUSE MODELS; A-BETA;
   APOPTOSIS; GLAUCOMA
AB Amyloid beta peptides (A beta) have been implicated in the pathogenesis of age-related macular degeneration (ARMD) and glaucoma. In this study, retinas of mice overexpressing A beta (Tg) were compared to those of wild-type mice (Wt) and analyzed for oxidative stress parameters. We observed a progressive decrease in all retinal cell layers, which was significantly greater in Tg mice at 14 months and culminated in loss of the outer retina at 18 months of age. We also observed higher levels of reactive oxygen species, glial fibrillary acidic protein, and hydroperoxide in Tg versus Wt mice (14 months). These effects were associated with phosphorylation/activation of the apoptosis signal kinase 1 and the p38 mitogen-activated kinase. Western blotting analysis revealed progressive increases in the levels of thioredoxin 1 and thioredoxin inhibitory protein in Tg compared to Wt mice. No changes were observed in the levels of thioredoxin reductase 1 (TrxR1): however, measurements of TrxR1 activity showed a 42.7 +/- 8% reduction in Tg mice versus Wt at 14 months of age. Our data suggest that A beta-mediated retinal neurotoxicity involves impairment of the thioredoxin system and enhanced oxidative stress, potentially implicating this mechanism in the pathogenesis of ARMD and glaucoma. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Liou, Gregory I.; Bartoli, Manuela] Georgia Hlth Sci Univ, Dept Ophthalmol, Augusta, GA 30912 USA.
   [Lamoke, Folami; Webster, Scott; Bartoli, Manuela] Georgia Hlth Sci Univ, Dept Pharmacol & Toxicol, Augusta, GA 30912 USA.
   [Ripandelli, Guido; Montemari, AnnaLisa] IRCCS Fdn GB Bietti, I-00161 Rome, Italy.
   [Maraschi, AnnaMaria] Univ Milan, Dipartimento Sci Biomol & Biotecnol, I-20133 Milan, Italy.
   [Martin, Pamela] Georgia Hlth Sci Univ, Dept Biochem & Mol Biol, Augusta, GA 30912 USA.
   [Marcus, Dennis M.] SE Retina Ctr, Augusta, GA 30909 USA.
C3 University System of Georgia; Augusta University; University System of
   Georgia; Augusta University; IRCCS - Fondazione "G.B. Bietti" per lo
   Studio e la Ricerca in Oftalmologia; University of Milan; University
   System of Georgia; Augusta University
RP Bartoli, M (通讯作者)，Georgia Hlth Sci Univ, Dept Ophthalmol, Augusta, GA 30912 USA.
EM mbartoli@georgiahealth.edu
RI Montemari, Anna Lisa/AAA-8807-2020
OI Montemari, Anna Lisa/0000-0001-9618-0007; Maraschi, Anna
   Maria/0000-0002-0766-1384
FU Department of Ophthalmology at Georgia Health Sciences University;
   Ricerca Finalizzata of the Italian Ministry of Health; IRCCS Fondazione
   GB Bietti
FX This study would not have been possible without the help of Dr. J.J.
   Buccafusco, Director of the Alzheimer's Center of Georgia Health
   Sciences University, who provided us with the double-transgenic AD mice.
   Unfortunately, Dr. Buccafusco has passed away and it is with our utmost
   sorrow that we dedicate this study to his memory. We also thank Dr.
   Alvin Terry for facilitating the continued use of the double-transgenic
   AD mice. We also thank Chaunte Stampley for her excellent technical
   support. These authors are also grateful to the sponsors of this study:
   the Department of Ophthalmology at Georgia Health Sciences University,
   the Ricerca Finalizzata of the Italian Ministry of Health, and the IRCCS
   Fondazione GB Bietti.
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NR 54
TC 12
Z9 12
U1 0
U2 7
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 AUG 1
PY 2012
VL 53
IS 3
BP 577
EP 588
DI 10.1016/j.freeradbiomed.2012.04.010
PG 12
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 986DP
UT WOS:000307321500019
PM 22564527
DA 2022-11-30
ER

PT J
AU Schmeer, CW
   Wohl, SG
   Isenmann, S
AF Schmeer, Christian W.
   Wohl, Stefanie G.
   Isenmann, Stefan
TI Cell-replacement therapy and neural repair in the retina
SO CELL AND TISSUE RESEARCH
LA English
DT Review
DE Retinal transplant; Stem cell; Retinal pigment epithelium;
   Photoreceptor; Retinal ganglion cell; Muller glia; Microglia
ID EMBRYONIC STEM-CELLS; MARROW-DERIVED CELLS; GANGLION-LIKE CELLS; MULLER
   GLIAL-CELLS; ADULT-MOUSE EYE; PIGMENT-EPITHELIUM; PROGENITOR CELLS;
   IN-VITRO; CNS NEURONS; RAT MODEL
AB Visual impairment severely affects the quality of life of patients and their families and is also associated with a deep economic impact. The most common pathologies responsible for visual impairment and legally defined blindness in developed countries include age-related macular degeneration, glaucoma and diabetic retinopathy. These conditions share common pathophysiological features: dysfunction and loss of retinal neurons. To date, two main approaches are being taken to develop putative therapeutic strategies: neuroprotection and cell replacement. Cell replacement is a novel therapeutic approach to restore visual capabilities to the degenerated adult neural retina and represents an emerging field of regenerative neurotherapy. The discovery of a population of proliferative cells in the mammalian retina has raised the possibility of harnessing endogenous retinal stem cells to elicit retinal repair. Furthermore, the development of suitable protocols for the reprogramming of differentiated somatic cells to a pluripotent state further increases the therapeutic potential of stem-cell-based technologies for the treatment of major retinal diseases. Stem-cell transplantation in animal models has been most effectively used for the replacement of photoreceptors, although this therapeutic approach is also being used for inner retinal pathologies. In this review, we discuss recent advances in the development of cell-replacement approaches for the treatment of currently incurable degenerative retinal diseases.
C1 [Schmeer, Christian W.; Wohl, Stefanie G.] Univ Hosp Jena, Hans Berger Clin Neurol, D-07747 Jena, Germany.
   [Isenmann, Stefan] HELIOS Klin, Dept Neurol, Wuppertal, Germany.
   [Wohl, Stefanie G.; Isenmann, Stefan] Univ Witten, Herdecke, Germany.
C3 Friedrich Schiller University of Jena; Helios Kliniken; Witten Herdecke
   University
RP Schmeer, CW (通讯作者)，Univ Hosp Jena, Hans Berger Clin Neurol, Erlanger Allee 101, D-07747 Jena, Germany.
EM christian.schmeer@med.uni-jena.de
RI Isenmann, Stefan/AAJ-3788-2020; Wohl, Stefanie/I-1590-2019
OI Wohl, Stefanie/0000-0003-2559-7678; Schmeer,
   Christian/0000-0002-2289-0126
FU Deutsche Forschungsgemeinschaft [DFG/SCHM2639/1-1/565547];
   Interdisziplinares Zentrum fur Klinische Forschung (IZKF/BMBF);
   University of Witten/Herdecke
FX Our group has received support from the Deutsche Forschungsgemeinschaft
   (DFG/SCHM2639/1-1/565547) to C. S., the Interdisziplinares Zentrum fur
   Klinische Forschung (IZKF/BMBF) to S. I. and a Scholarship from the
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NR 121
TC 18
Z9 18
U1 0
U2 34
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0302-766X
EI 1432-0878
J9 CELL TISSUE RES
JI Cell Tissue Res.
PD JUL
PY 2012
VL 349
IS 1
BP 363
EP 374
DI 10.1007/s00441-012-1335-6
PG 12
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 960RF
UT WOS:000305405800028
PM 22354517
DA 2022-11-30
ER

PT J
AU Lee, E
   Rosca, EV
   Pandey, NB
   Popel, AS
AF Lee, Esak
   Rosca, Elena V.
   Pandey, Niranjan B.
   Popel, Aleksander S.
TI Small peptides derived from somatotropin domain-containing proteins
   inhibit blood and lymphatic endothelial cell proliferation, migration,
   adhesion and tube formation
SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
LA English
DT Article
DE Lymphatic endothelial cell; Blood endothelial cell; Endogenous
   somatotropin peptides; Transmembrane protein 45A human
ID GROWTH-FACTOR; MOLECULAR-MECHANISMS; VEGF-C; RECEPTOR;
   LYMPHANGIOGENESIS; GENE; ACTIVATION; EXPRESSION; LIGAND; NODE
AB Angiogenesis is thoroughly balanced and regulated in health; however, it is dysregulated in many diseases including cancer, age-related macular degeneration, cardiovascular diseases such as coronary and peripheral artery diseases and stroke, abnormal embryonic development, and abnormal wound healing. In addition to angiogenesis, lymphangiogenesis is pivotal for maintaining the immune system, homeostasis of body fluids and lymphoid organs; dysregulated lymphangiogenesis may cause inflammatory diseases and lymph node mediated tumor metastasis. Anti-angiogenic or anti-lymphangiogenic small peptides may play an important role as therapeutic agents normalizing angiogenesis or lymphangiogenesis in disease conditions. Several novel endogenous peptides derived from proteins containing a conserved somatotropin domain have been previously identified with the help of our bioinformatics-based methodology. These somatotropin peptides were screened for inhibition of angiogenesis and lymphangiogenesis using in vitro proliferation, migration, adhesion and tube formation assays with blood and lymphatic endothelial cells. We found that the peptides have the potential for inhibiting both angiogenesis and lymphangiogenesis. Focusing the study on the inhibition of lymphangiogenesis, we found that a peptide derived from the somatotropin conserved domain of transmembrane protein 45A human was the most potent lymphangiogenesis inhibitor, blocking lymphatic endothelial cell migration, adhesion, and tube formation. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Rosca, Elena V.; Pandey, Niranjan B.; Popel, Aleksander S.] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA.
   [Lee, Esak; Popel, Aleksander S.] Johns Hopkins Univ, Sch Engn, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA.
C3 Johns Hopkins University; Johns Hopkins University
RP Popel, AS (通讯作者)，Johns Hopkins Univ, Sch Med, Dept Biomed Engn, 611 Traylor Bldg,720 Rutland Ave, Baltimore, MD 21205 USA.
EM apopel@jhu.edu
RI Popel, Aleksander S/A-6724-2009; Lee, Esak/AAC-6403-2020
OI Lee, Esak/0000-0002-5328-6677; Popel, Aleksander/0000-0002-6706-9235
FU National Institutes of Health [R21 CA131931, R01 CA138264]; NATIONAL
   CANCER INSTITUTE [R21CA131931, R01CA138264] Funding Source: NIH
   RePORTER; NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL101200]
   Funding Source: NIH RePORTER
FX This work was supported by the National Institutes of Health grants R21
   CA131931 and R01 CA138264.
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NR 37
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Z9 25
U1 1
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1357-2725
EI 1878-5875
J9 INT J BIOCHEM CELL B
JI Int. J. Biochem. Cell Biol.
PD DEC
PY 2011
VL 43
IS 12
BP 1812
EP 1821
DI 10.1016/j.biocel.2011.08.020
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA 854JV
UT WOS:000297491700020
PM 21920451
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Howells, O
   Eperjesi, F
   Bartlett, H
AF Howells, Olivia
   Eperjesi, Frank
   Bartlett, Hannah
TI Measuring macular pigment optical density in vivo: a review of
   techniques
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Review
DE Fundus autofluorescence; Fundus reflectometry; Heterochromatic flicker
   photometry; Macular pigment; Macular pigment optical density; Motion
   photometry; Raman spectroscopy
ID HETEROCHROMATIC FLICKER PHOTOMETRY; AGE-RELATED MACULOPATHY; SCANNING
   LASER OPHTHALMOSCOPE; HUMAN CONE PHOTORECEPTORS; SPATIAL-DISTRIBUTION;
   FUNDUS AUTOFLUORESCENCE; LUTEIN SUPPLEMENTATION; HUMAN RETINA; SERUM
   CONCENTRATIONS; PRIMATE RETINAS
AB Macular pigment has been the focus of much attention in recent years, as a potential modifiable risk factor for age-related macular degeneration. This interest has been heightened by the ability to measure macular pigment optical density (MPOD) in vivo.
   A systematic literature search was undertaken to identify all available papers that have used in vivo MPOD techniques. The papers were reviewed, and all relevant information was incorporated into this article.
   Measurement of MPOD is achievable with a wide range of techniques, which are typically categorized into one of two groups: psychophysical (requiring a response from the subject) or objective (requiring minimal input from the subject). The psychophysical methods include heterochromatic flicker photometry and minimum motion photometry. The objective methods include fundus reflectometry, fundus autofluorescence, resonance Raman spectroscopy and visual evoked potentials. Even within the individual techniques, there is often much variation in how data is obtained and processed.
   This review comprehensively details the procedure, instrumentation, assumptions, validity and reliability of each MPOD measurement technique currently available, along with their respective advantages and disadvantages. This leads us to conclude that development of a commercial instrument, based on fundus reflectometry or fundus autofluorescence, would be beneficial to macular pigment research and would support MPOD screening in a clinical setting.
C1 [Howells, Olivia; Eperjesi, Frank; Bartlett, Hannah] Aston Univ, Sch Life & Hlth Sci, Ophthalm Res Grp, Birmingham B4 7ET, W Midlands, England.
C3 Aston University
RP Howells, O (通讯作者)，Aston Univ, Sch Life & Hlth Sci, Ophthalm Res Grp, Birmingham B4 7ET, W Midlands, England.
EM o.howells@aston.ac.uk
RI Eperjesi, Frank/A-9275-2013
OI Eperjesi, Frank/0000-0003-4358-0095; Bartlett Eperjesi, Hannah
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NR 151
TC 89
Z9 91
U1 1
U2 29
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
EI 1435-702X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD MAR
PY 2011
VL 249
IS 3
BP 315
EP 347
DI 10.1007/s00417-010-1577-5
PG 33
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 735XO
UT WOS:000288454200002
PM 21221629
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Davuluri, G
   Espina, V
   Petricoin, EF
   Ross, M
   Deng, J
   Liotta, LA
   Glaser, BM
AF Davuluri, Geetanjali
   Espina, Virginia
   Petricoin, Emanuel F., III
   Ross, Mark
   Deng, Jianghong
   Liotta, Lance A.
   Glaser, Bert M.
TI Activated VEGF Receptor Shed Into the Vitreous in Eyes With Wet AMD A
   New Class of Biomarkers in the Vitreous With Potential for Predicting
   the Treatment Timing and Monitoring Response
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; PHASE PROTEIN MICROARRAYS; MACULAR
   DEGENERATION; DIABETIC-RETINOPATHY; RANIBIZUMAB; CANCER; FLUID;
   AUTOPHOSPHORYLATION; PROGRESSION; CYTOKINES
AB Objective: To examine whether phosphorylated vascular endothelial growth factor (VEGF) receptors shed into the vitreous reflect the ongoing retinal and choroidal signal pathway activity in wet age-related macular degeneration (AMD).
   Methods: Vitreous samples obtained immediately prior to anti-VEGF injection from 11 patients with choroidal neovascularization were analyzed using reverse-phase microarrays. Two patients had samples collected at the time of injection and 1 month later. Samples from 5 patients were collected prior to vitrectomy for macular hole, epiretinal membrane, or retinal detachment.
   Results: Phosphorylated forms of VEGF receptor (VEGFR Y996 and Y1175), platelet-derived growth factor receptor beta (PDGFR beta Y716 and Y751), and c-KIT (Y703) were present in the Vitreous. A significant difference in PDGFR beta Y751 (P<.002), VEGFR Y996 (P<.04), and VEGFR Y1175 (P<.006), but not c-KIT Y703 (P<.05) or PDGFR beta Y716 (P<.96), was noted for the responders to treatment (n=5) compared with nonresponders (n = 6) and controls (n = 5).
   Conclusions: Vitreous levels of activated receptors constitute a new class of biomarkers. Activated forms of VEGF and PDGF receptors, previously not known to exist in the vitreous, correlate with response to anti-VEGF therapy. These findings could provide the basis for the development of individualized treatment and discovery of new therapeutic targets.
C1 [Davuluri, Geetanjali; Glaser, Bert M.] Natl Retina Inst, Towson, MD 21204 USA.
   [Espina, Virginia; Petricoin, Emanuel F., III; Ross, Mark; Deng, Jianghong; Liotta, Lance A.] George Mason Univ, Manassas, VA USA.
C3 George Mason University
RP Glaser, BM (通讯作者)，Natl Retina Inst, 901 Dulaney Valley Rd,Ste 200, Towson, MD 21204 USA.
EM rclasson@nationalretina.org
OI Espina, Virginia/0000-0001-5080-5972
FU George Mason University; NATIONAL EYE INSTITUTE [R21EY018942] Funding
   Source: NIH RePORTER
FX Funding/Support: This study was supported in part by George Mason
   University.
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NR 31
TC 30
Z9 32
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0003-9950
EI 1538-3601
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD MAY
PY 2009
VL 127
IS 5
BP 613
EP 621
DI 10.1001/archophthalmol.2009.88
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 442NK
UT WOS:000265847700003
PM 19433709
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU Lornejad-Schafer, MR
   Lambert, C
   Breithaupt, DE
   Biesalski, HK
   Frank, J
AF Lornejad-Schaefer, Mohammad Reza
   Lambert, Christine
   Breithaupt, Dietmar E.
   Biesalski, Hans K.
   Frank, Juergen
TI Solubility, uptake and biocompatibility of lutein and zeaxanthin
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   micelles
SO EUROPEAN JOURNAL OF NUTRITION
LA English
DT Article
DE lutein; zeaxanthin; age related macular degeneration (AMD); retinal
   pigment epithelium (RPE); micellation
ID MACULAR DEGENERATION; OXIDATIVE STRESS; GENE-EXPRESSION; ARPE-19 CELLS;
   CAROTENOIDS; IDENTIFICATION; PATHOGENESIS
AB Carotenoids lutein and zeaxanthin are proposed to protect ocular tissues from free-radical damage that can cause cataract and age-related macular degeneration (AMD). They accumulate selectively in the lens and macular region of the retina. Changes in the retinal pigment epithelium are characteristic in AMD. Efficient uptake is essential to study the intracellular effects of carotenoids in cell cultures. For in vitro experiments carotenoids are often dissolved in organic solvents like tetrahydrofuran (THF), dimethylsulfoxide (DMSO) and n-hexane, but difficulties have been associated with these application methods. Recently, O'Sullivan et al. (SM O'Sullivan et al., Br J Nutr 91 (2004) 757) developed a method whereby carotenoids could be delivered to cultured cells without the cytotoxic side effects often observed when organic solvents are used. We modified this method and investigated the effects of different carotenoid-formulations (ethanol/Tween40, methanol/tween40 and acetone/Tween40) on the uptake of lutein and zeaxanthin by differentiated ARPE-19 cells, cell viability and the expression of the "stress" gene HO-1, which is easily induced by a range of stimuli including chemical and physical agents. Micelle formulations prepared with ethanol/Tween40 resulted in the lowest LDH release, the highest carotenoid uptake and the lowest stress response (changes in HO-1 mRNA expression).
C1 Univ Hohenheim, Inst Biol Chem & Nutr, D-70593 Stuttgart, Germany.
   Univ Hohenheim, Inst Food Chem, D-7000 Stuttgart, Germany.
C3 University Hohenheim; University Hohenheim
RP Frank, J (通讯作者)，Univ Hohenheim, Inst Biol Chem & Nutr, Garbenstr 30, D-70593 Stuttgart, Germany.
EM frank140@uni-hohenheim.de
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NR 23
TC 18
Z9 19
U1 1
U2 15
PU DR DIETRICH STEINKOPFF VERLAG
PI DARMSTADT
PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY
SN 1436-6207
J9 EUR J NUTR
JI Eur. J. Nutr.
PD MAR
PY 2007
VL 46
IS 2
BP 79
EP 86
DI 10.1007/s00394-006-0635-6
PG 8
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA 137LT
UT WOS:000244294800003
PM 17225922
DA 2022-11-30
ER

PT J
AU Ferreira, MM
   Antunes-Foschini, R
   Furtado, JM
AF Ferreira, Manuela Molina
   Antunes-Foschini, Rosalia
   Furtado, Joao M.
TI Causes of functional low vision in a Brazilian rehabilitation service
SO SCIENTIFIC REPORTS
LA English
DT Article
ID VISUAL IMPAIRMENT; BLINDNESS; CHILDREN
AB There is limited information on functional low vision (FLV) in Latin America, especially in individuals under 50 years of age. In the present study, we retrospectively evaluated the medical records of 1393 consecutive subjects seen at a Brazilian tertiary rehabilitation service, from February 2009 to June 2016. We collected sociodemographic, clinical data, and information on optical aids and spectacle prescription. Subjects were divided into three age groups: 0 to 14 years old (children), 15 to 49 years old (young adults), and 50 years or older (older adults). The main etiologies leading to FLV in children were cerebral visual impairment (27.9%), ocular toxoplasmosis (8.2%), and retinopathy of prematurity (7.8%). In young adults, retinitis pigmentosa (7.4%) and cone/rod dystrophy (6.5%) were the most frequent, while in older adults, age-related macular degeneration (25.3%) and diabetic retinopathy (18.0%) were the leading causes. Our results indicate that preventable diseases are important causes of FLV in children in the area, and proper prenatal care could reduce their burden. The increasing life expectancy in Latin America and the diabetes epidemic are likely to increase the demand for affordable, people-centered rehabilitation centers, and their integration into health services should be planned accordingly.
C1 [Ferreira, Manuela Molina; Antunes-Foschini, Rosalia] Univ Sao Paulo, Hosp Clin, Ribeirao Preto Med Sch, Ribeirao Preto, SP, Brazil.
   [Ferreira, Manuela Molina; Furtado, Joao M.] Univ Sao Paulo, Preto Med Sch, Dept Ophthalmol Otorhinolaryngol & Head & Neck Su, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil.
C3 Universidade de Sao Paulo; Universidade de Sao Paulo
RP Furtado, JM (通讯作者)，Univ Sao Paulo, Preto Med Sch, Dept Ophthalmol Otorhinolaryngol & Head & Neck Su, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil.
EM furtadojm@gmail.com
FU Biostatistics Service of the School of the RibeirAo Preto Medical School
FX The authors thank the Biostatistics Service of the School of the
   RibeirAo Preto Medical School, in the person of Tatiana Reis Icuma.
CR [Anonymous], 2016, R LANG ENV STAT COMP
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NR 25
TC 0
Z9 0
U1 0
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 FEB 18
PY 2022
VL 12
IS 1
AR 2807
DI 10.1038/s41598-022-06798-0
PG 7
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA ZD0MB
UT WOS:000757901500046
PM 35181704
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Mulfaul, K
   Russell, JF
   Voigt, AP
   Stone, EM
   Tucker, BA
   Mullins, RF
AF Mulfaul, Kelly
   Russell, Jonathan F.
   Voigt, Andrew P.
   Stone, Edwin M.
   Tucker, Budd A.
   Mullins, Robert F.
TI The Essential Role of the Choriocapillaris in Vision: Novel Insights
   from Imaging and Molecular Biology
SO ANNUAL REVIEW OF VISION SCIENCE
LA English
DT Review
DE choroid; age-related macular degeneration; endothelial cell; single-cell
   RNA sequencing; induced pluripotent stem cell; iPSC
ID RETINAL-PIGMENT EPITHELIUM; C-REACTIVE PROTEIN; CHOROIDAL
   ENDOTHELIAL-CELLS; IN-VITRO MODEL; MACULAR-DEGENERATION; BRUCHS
   MEMBRANE; GEOGRAPHIC ATROPHY; MORPHOMETRIC-ANALYSIS; VESSEL FORMATION;
   SPECTRAL-DOMAIN
AB The choriocapillaris, a dense capillary network located at the posterior pole of the eye, is essential for supporting normal vision, supplying nutrients, and removing waste products from photoreceptor cells and the retinal pigment epithelium. The anatomical location, heterogeneity, and homeostatic interactions with surrounding cell types make the choroid complex to study both in vivo and in vitro. Recent advances in single-cell RNA sequencing, in vivo imaging, and in vitro cell modeling are vastly improving our knowledge of the choroid and its role in normal health and in age-related macular degeneration (AMD). Histologically, loss of endothelial cells (ECs) of the choriocapillaris occurs early in AMD concomitant with elevated formation of the membrane attack complex of complement. Advanced imaging has allowed us to visualize early choroidal blood flow changes in AMD in living patients, supporting histological findings of loss of choroidal ECs. Single-cell RNA sequencing is being used to characterize choroidal cell types transcriptionally and discover their altered patterns of gene expression in aging and disease. Advances in induced pluripotent stem cell protocols and 3D cultures will allow us to closely mimic the in vivo microenvironment of the choroid in vitro to better understand the mechanism leading to choriocapillaris loss in AMD.
C1 [Mullins, Robert F.] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA 52240 USA.
   Univ Iowa, Inst Vis Res, Iowa City, IA USA.
C3 University of Iowa; University of Iowa
RP Mullins, RF (通讯作者)，Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA 52240 USA.
EM Robert-Mullins@uiowa.edu
FU Elmer and Sylvia Sramek Charitable Trust; National Institutes of Health
   [EY024605, EY025580]; Research to Prevent Blindness
FX This work is supported in part by the Elmer and Sylvia Sramek Charitable
   Trust, National Institutes of Health grants EY024605 and EY025580, and
   Research to Prevent Blindness. The authors gratefully acknowledge the
   eye donors and their families whose selfless acts of service made this
   research possible.
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NR 93
TC 0
Z9 0
U1 1
U2 1
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA
SN 2374-4642
EI 2374-4650
J9 ANNU REV VIS SCI
JI ANNU. REV. VIS. SCI.
PY 2022
VL 8
BP 33
EP 52
DI 10.1146/annurev-vision-100820-085958
PG 20
WC Neurosciences; Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Ophthalmology
GA 4Q7IK
UT WOS:000856252600002
PM 36108103
DA 2022-11-30
ER

PT J
AU Zhou, M
   Geathers, JS
   Grillo, SL
   Weber, SR
   Wang, WW
   Zhao, YJ
   Sundstrom, JM
AF Zhou, Mi
   Geathers, Jasmine S.
   Grillo, Stephanie L.
   Weber, Sarah R.
   Wang, Weiwei
   Zhao, Yuanjun
   Sundstrom, Jeffrey M.
TI Role of Epithelial-Mesenchymal Transition in Retinal Pigment Epithelium
   Dysfunction
SO FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
LA English
DT Review
DE RPE; dedifferentiation; RPE dysfunction; EMT; UPR; retinal degeneration
ID INTRARETINAL HYPERREFLECTIVE FOCI; ENDOPLASMIC-RETICULUM STRESS;
   UNFOLDED PROTEIN RESPONSE; MACULAR DEGENERATION; TGF-BETA; PROLIFERATIVE
   VITREORETINOPATHY; EXTRACELLULAR-MATRIX; SUBRETINAL FIBROSIS;
   CELL-PROLIFERATION; SIGNALING PATHWAY
AB Retinal pigment epithelial (RPE) cells maintain the health and functional integrity of both photoreceptors and the choroidal vasculature. Loss of RPE differentiation has long been known to play a critical role in numerous retinal diseases, including inherited rod-cone degenerations, inherited macular degeneration, age-related macular degeneration, and proliferative vitreoretinopathy. Recent studies in post-mortem eyes have found upregulation of critical epithelial-mesenchymal transition (EMT) drivers such as TGF-beta, Wnt, and Hippo. As RPE cells become less differentiated, they begin to exhibit the defining characteristics of mesenchymal cells, namely, the capacity to migrate and proliferate. A number of preclinical studies, including animal and cell culture experiments, also have shown that RPE cells undergo EMT. Taken together, these data suggest that RPE cells retain the reprogramming capacity to move along a continuum between polarized epithelial cells and mesenchymal cells. We propose that movement along this continuum toward a mesenchymal phenotype be defined asRPE Dysfunction.Potential mechanisms include impaired tight junctions, accumulation of misfolded proteins and dysregulation of several key pathways and molecules, such as TGF-beta pathway, Wnt pathway, nicotinamide, microRNA 204/211 and extracellular vesicles. This review synthesizes the evidence implicating EMT of RPE cells in post-mortem eyes, animal studies, primary RPE, iPSC-RPE and ARPE-19 cell lines.
C1 [Zhou, Mi; Geathers, Jasmine S.; Grillo, Stephanie L.; Weber, Sarah R.; Zhao, Yuanjun; Sundstrom, Jeffrey M.] Penn State Coll Med, Dept Ophthalmol, Hershey, PA 17033 USA.
   [Wang, Weiwei] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Houston, TX USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE);
   Pennsylvania State University; Penn State Health; University of Texas
   System; University of Texas Health San Antonio
RP Sundstrom, JM (通讯作者)，Penn State Coll Med, Dept Ophthalmol, Hershey, PA 17033 USA.
EM jsundstrom@pennstatehealth.psu.edu
OI Grillo, Stephanie/0000-0001-7208-300X; Zhou, Mi/0000-0003-1831-1221
FU scholarship of Bennett and Inez Chotiner Early Career Professor in
   Ophthalmology
FX This study was funded in part by the scholarship of Bennett and Inez
   Chotiner Early Career Professor in Ophthalmology (JS).
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NR 136
TC 46
Z9 47
U1 1
U2 9
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 2296-634X
J9 FRONT CELL DEV BIOL
JI Front. Cell. Dev. Biol.
PD JUN 25
PY 2020
VL 8
AR 501
DI 10.3389/fcell.2020.00501
PG 13
WC Cell Biology; Developmental Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Developmental Biology
GA MK9VR
UT WOS:000549127500001
PM 32671066
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Denlinger, B
   Helft, Z
   Telias, M
   Lorach, H
   Palanker, D
   Kramer, RH
AF Denlinger, Bristol
   Helft, Zachary
   Telias, Michael
   Lorach, Henri
   Palanker, Daniel
   Kramer, Richard H.
TI Local photoreceptor degeneration causes local pathophysiological
   remodeling of retinal neurons
SO JCI INSIGHT
LA English
DT Article
ID VISUAL RESPONSES; GANGLION-CELLS; RAT RETINA; RD1
AB Vision loss in age-related macular degeneration (AMD) stems from disruption of photoreceptor cells in the macula, the central retinal area required for high-acuity vision. Mice and rats have no macula, but surgical insertion of a subretinal implant can induce localized photoreceptor degeneration due to chronic separation from retinal pigment epithelium, simulating a key aspect of AMD. We find that the implant-induced loss of photoreceptors in rat retina leads to local changes in the physiology of downstream retinal ganglion cells (RGCs), similar to changes in RGCs of rodent models of retinitis pigmentosa (RP), an inherited disease causing retina-wide photoreceptor degeneration. The local implant-induced changes in RGCs include enhanced intrinsic excitability leading to accelerated spontaneous firing, increased membrane permeability to fluorescent dyes, and enhanced photosensitization by azobenzene photoswitches. The local physiological changes are correlated with an increase in retinoic acid receptor-induced (RAR-induced) gene transcription, the key process underlying retinal remodeling in mouse models of RP. Hence the loss of photoreceptors, whether by local physical perturbation or by inherited mutation, leads to a stereotypical set of pathophysiological consequences in RGCs. These findings implicate RAR as a possible common therapeutic target for reversing the signal-corrupting effects of retinal remodeling in both RP and AMD.
C1 [Denlinger, Bristol; Helft, Zachary; Telias, Michael; Kramer, Richard H.] Univ Calif Berkeley, Dept Mol & Cell Biol, 121 Life Sci Bldg, Berkeley, CA 94720 USA.
   [Helft, Zachary; Kramer, Richard H.] Univ Calif Berkeley, Vis Sci Grad Grp, Berkeley, CA 94720 USA.
   [Lorach, Henri; Palanker, Daniel] Stanford Univ, Hansen Expt Phys Lab, Stanford, CA 94305 USA.
   [Palanker, Daniel] Stanford Univ, Dept Ophthalmol, Stanford, CA 94305 USA.
C3 University of California System; University of California Berkeley;
   University of California System; University of California Berkeley;
   Stanford University; Stanford University
RP Kramer, RH (通讯作者)，Univ Calif Berkeley, Dept Mol & Cell Biol, 121 Life Sci Bldg, Berkeley, CA 94720 USA.
EM rhkramer@berkeley.edu
OI Telias, Michael/0000-0002-7632-6942; LORACH, HENRI/0000-0003-4337-2798;
   Palanker, Daniel/0000-0002-0480-3025
FU National Eye Institute [R01EY024334, R24EY023937, P30EY003176]; Thome
   Foundation; Foundation for Fighting Blindness; NIH [R01-EY-018608,
   R01-EY-027786]; Department of Defense [W81XWH-15-1-0009]; Stanford
   Institute of Neuroscience; Research to Prevent Blindness
FX This work was supported by grants from the National Eye Institute
   (R01EY024334, R24EY023937, and P30EY003176), the Thome Foundation, and
   the Foundation for Fighting Blindness. DP and HL were supported by the
   NIH (R01-EY-018608, R01-EY-027786), the Department of Defense
   (W81XWH-15-1-0009), the Stanford Institute of Neuroscience, and Research
   to Prevent Blindness.
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NR 29
TC 10
Z9 10
U1 0
U2 3
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA
EI 2379-3708
J9 JCI INSIGHT
JI JCI Insight
PD JAN 30
PY 2020
VL 5
IS 2
AR e132114
DI 10.1172/jci.insight.132114
PG 9
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA KH7JT
UT WOS:000510827200010
PM 31846440
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Mazzilli, JL
   Snook, JD
   Simmons, K
   Domozhirov, AY
   Garcia, CA
   Wetsel, RA
   Zsigmond, EM
   Westenskow, PD
AF Mazzilli, John L.
   Snook, Joshua D.
   Simmons, Ken
   Domozhirov, Aleksey Y.
   Garcia, Charles A.
   Wetsel, Rick A.
   Zsigmond, Eva M.
   Westenskow, Peter D.
TI A Preclinical Safety Study of Human Embryonic Stem Cell-Derived Retinal
   Pigment Epithelial Cells for Macular Degeneration
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
DE macular degeneration; stem cell; retinal pigment epithelium; cell
   therapy
ID MICE; PREVALENCE; DERIVATION
AB Purpose: Age-related macular degeneration (AMD) is a common disease trending towards epidemic proportions and is a leading cause of irreversible vision loss in people over the age of 65. A pathomechanism of AMD is death and/or dysfunction of retinal pigment epithelial (RPE) cells; RPE loss invariably results in photoreceptor atrophy. Treatment options for AMD are very limited, and include vitamin supplements and lifestyle changes. An exciting potential therapy currently being tested in clinical trials is transplantation of stem cell-derived RPE. Methods: We developed a NIH-registered embryonic stem line (CR-4), and in this study set out to determine if CR4-RPE are tolerated in normal mice and in murine models of retinal degeneration by injecting a bolus of CR4-RPE cells in the subretinal space of immunosuppressed wild-type, Mer mutant (Merkd), and Elovl4 deficient mice. Results: Mice with CR-RPE grafts were monitored daily, were examined routinely using OCT, and histology was prepared and examined at terminal end-points. Based on the parameters of the study, none of the animals with CR-RPE grafts (n=36) experienced any obvious adverse reactions. Conclusions: We conclude that transplanted CR-4 hES-derived RPE cells are well tolerated in immunosuppressed healthy and dystrophic murine retinas.
C1 [Mazzilli, John L.; Simmons, Ken; Domozhirov, Aleksey Y.; Wetsel, Rick A.; Zsigmond, Eva M.] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Brown Fdn, McGovern Med Sch, Houston, TX 77030 USA.
   [Snook, Joshua D.; Westenskow, Peter D.] Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA.
   [Garcia, Charles A.] Univ Texas Hlth Sci Ctr Houston, Ruiz Dept Ophthalmol & Visual Sci, McGovern Med Sch, Houston, TX 77030 USA.
C3 University of Texas System; University of Texas Health Science Center
   Houston; Baylor College of Medicine; University of Texas System;
   University of Texas Health Science Center Houston
RP Westenskow, PD (通讯作者)，F Hoffman La Roche Ltd, Ocular Technol 120, CH-4070 Basel, Switzerland.
EM peter.westenskow@roche.com
FU Clive and Nancy Runnells Embryonic Stem Cell Research Fund at The
   University of Texas Health Science Center at Houston; Baylor College of
   Medicine [2P30EY002520]
FX This work was funded by the Clive and Nancy Runnells Embryonic Stem Cell
   Research Fund (in memory of Pierce Runnells) at The University of Texas
   Health Science Center at Houston, by Core Grant 2P30EY002520 (Baylor
   College of Medicine), and by institutional grants to the Department of
   Ophthalmology at Baylor College of Medicine.
CR Brechner RJ, 2011, AM J OPHTHALMOL, V151, P887, DOI 10.1016/j.ajo.2010.11.017
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NR 23
TC 3
Z9 3
U1 0
U2 9
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1080-7683
EI 1557-7732
J9 J OCUL PHARMACOL TH
JI J. Ocular Pharmacol. Ther.
PD JAN 1
PY 2020
VL 36
IS 1
BP 65
EP 69
DI 10.1089/jop.2019.0039
EA OCT 2019
PG 5
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA KF7IY
UT WOS:000489248900001
PM 31596637
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Ohayon, A
   Semoun, O
   Caillaux, V
   Jung, C
   Lay, B
   Miere, A
   Souied, EH
   Blanco-Garavito, R
AF Ohayon, Avi
   Semoun, Oudy
   Caillaux, Violaine
   Jung, Camille
   Lay, Bruno
   Miere, Alexandra
   Souied, Eric H.
   Blanco-Garavito, Rocio
TI Reliability and Reproducibility of Pigment Epithelial Detachment Volume
   Measurements in AMD Using a New Tool: ReVAnalyzer
SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR DEGENERATION; CHOROIDAL
   NEOVASCULARIZATION; RANIBIZUMAB
AB BACKGROUND AND OBJECTIVE: To describe and present the reliability and reproducibility of a new software, Retinal Volume Analyzer (ReVAnalyzer), for pigment epithelium detachment (PED) volume quantification.
   PATIENTS AND METHODS: This is a retrospective study including patients with PEDs secondary to exudative age-related macular degeneration (AMD). Macular volume scans on spectral-domain optical coherence tomography on enhanced depth imaging mode were performed in all eyes. Image batches were then exported in .xml format to the ReVA, nalyzer software. A semiautomated PED volume measurement was performed by three independent readers (RBG, VC, OS) twice, at the beginning and end of a 15-day period. Bland-Altman assessment for agreement was used to compare intra- and interobserver observations.
   RESULTS: Twenty eyes of 20 patients presenting with PED were analyzed. Bland-Altman analysis indicated a good agreement between inter- and intraobserver measurements. The intraclass correlation coefficient for intraobserver PED volume measurements and between the three observers (interobserver) was greater than 0.99, demonstrating high reproducibility and consistency of the methodology.
   CONCLUSIONS: ReVAnalyzer is a reliable tool that can assist in the analysis of PED volume with high reproducibility. This type of specific retinal volume analysis can be of help for monitoring disease activity and therapeutic response in AMD.
C1 [Ohayon, Avi; Semoun, Oudy; Caillaux, Violaine; Jung, Camille; Miere, Alexandra; Souied, Eric H.; Blanco-Garavito, Rocio] Univ Paris Est Creteil, Ctr Hosp Intercommunal Creteil, Dept Ophthalmol, 40 Ave Verdun, F-94000 Creteil, France.
   [Jung, Camille] Ctr Hosp Intercommunal Creteil, Ctr Invest Clin, Creteil, France.
   [Lay, Bruno] ADCIS, St Contest, France.
C3 Universite Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil; Institut
   National de la Sante et de la Recherche Medicale (Inserm); Universite
   Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil
RP Ohayon, A (通讯作者)，Univ Paris Est Creteil, Ctr Hosp Intercommunal Creteil, Dept Ophthalmol, 40 Ave Verdun, F-94000 Creteil, France.
EM aviohayonmd@gmail.com
RI Miere, Alexandra/AIC-4074-2022; Ohayon, Avi/R-2676-2018
OI Miere, Alexandra/0000-0003-4123-8210; Ohayon, Avi/0000-0002-4435-8659;
   JUNG, Camille/0000-0001-8486-8939
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NR 30
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 SEP
PY 2019
VL 50
IS 9
BP E242
EP E249
DI 10.3928/23258160-20190905-16
PG 8
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA JC5LI
UT WOS:000489323500004
PM 31589765
DA 2022-11-30
ER

PT J
AU Shatz, W
   Aaronson, J
   Yohe, S
   Kelley, RF
   Kalia, YN
AF Shatz, Whitney
   Aaronson, Jeffrey
   Yohe, Stefan
   Kelley, Robert F.
   Kalia, Yogeshvar N.
TI Strategies for modifying drug residence time and ocular bioavailability
   to decrease treatment frequency for back of the eye diseases
SO EXPERT OPINION ON DRUG DELIVERY
LA English
DT Review
DE Posterior eye diseases; intravitreal injection; long-acting delivery;
   ocular devices; slow release formulations; pharmacokinetic modifiers
ID SINGLE INTRAVITREAL INJECTION; VEGF TRAP-EYE; MACULAR DEGENERATION;
   SUSTAINED-RELEASE; POSTERIOR SEGMENT; HALF-LIFE; INTRAOCULAR
   PHARMACOKINETICS; ALBUMIN NANOPARTICLES; POLYETHYLENE-GLYCOL; GEOGRAPHIC
   ATROPHY
AB Introduction: Treating posterior eye diseases has become a major area of focus for pharmaceutical and biotechnology companies. Current standard of care for treating posterior eye diseases relies on administration via intravitreal injection. Although effective, this is not without complications and there is great incentive to develop longer-acting therapeutics and/or sustained release delivery systems. Here, we present an overview of emerging technologies for delivery of biologics to the back of the eye. Areas covered: Posterior eye diseases, intravitreal injection, age-related macular degeneration, anti-VEGF, ocular pharmacokinetics, novel technologies to extend half-life, in vivo models, translation to the clinic, and hurdles to effective patient care. Expert opinion: Posterior eye diseases are a worldwide public health issue. Although anti-VEGF molecules represent a major advance for treating diseases involving choroidal neovascularization, frequent injection can be burdensome for patients and clinicians. There is a need for effective and patient-friendly treatments for posterior eye diseases. Many technologies that enable long-acting delivery to the back of the eye are being evaluated. However, successful development of novel therapies and delivery technologies is hampered by a multitude of factors, including patient education, translatability of in vitro/in vivo preclinical data to the clinic, and regulatory challenges associated with novel technologies.
C1 [Shatz, Whitney] Genentech Inc, Dept Prot Chem, San Francisco, CA USA.
   [Shatz, Whitney; Kalia, Yogeshvar N.] Univ Geneva, Sch Pharmaceut Sci, CMU 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland.
   [Shatz, Whitney; Kalia, Yogeshvar N.] Univ Lausanne, Geneva, Switzerland.
   [Aaronson, Jeffrey; Yohe, Stefan; Kelley, Robert F.] Genentech Inc, Dept Drug Delivery, San Francisco, CA USA.
C3 Roche Holding; Genentech; University of Geneva; University of Lausanne;
   Roche Holding; Genentech
RP Kalia, YN (通讯作者)，Univ Geneva, Sch Pharmaceut Sci, CMU 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland.
EM yogi.kalia@unige.ch
RI Kalia, Yogeshvar/M-4745-2019
OI Kalia, Yogeshvar/0000-0001-9049-5489; Shatz-Binder,
   Whitney/0000-0003-2996-501X
FU University of Geneva; Genentech
FX W Shatz, J Aaronson, S Yohe, and R Kelley are employees of, and were
   supported by, Genentech. Y Kalia is an employee of, and was funded by,
   the University of Geneva.
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NR 151
TC 18
Z9 18
U1 1
U2 31
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1742-5247
EI 1744-7593
J9 EXPERT OPIN DRUG DEL
JI Expert Opin. Drug Deliv.
PD JAN 2
PY 2019
VL 16
IS 1
BP 43
EP 57
DI 10.1080/17425247.2019.1553953
PG 15
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA HG0PQ
UT WOS:000454649700003
PM 30488721
DA 2022-11-30
ER

PT J
AU Zhang, LQ
   Zhu, L
   Zhang, YM
   Yang, YD
   Wu, YM
   Ma, WX
   Lan, Y
   You, JS
AF Zhang, Luoqiang
   Zhu, Lei
   Zhang, Yuming
   Yang, Yudong
   Wu, Yimin
   Ma, Weixin
   Lan, Yu
   You, Jingsong
TI Experimental and Theoretical Studies on Ru(II)-Catalyzed Oxidative
   C-H/C-H Coupling of Phenols with Aromatic Amides Using Air as Oxidant:
   Scope, Synthetic Applications, and Mechanistic Insights
SO ACS CATALYSIS
LA English
DT Article
DE C-H activation; ruthenium catalysis; oxidative C-H/C-H cross-coupling;
   dual chelation-assisted strategy; 2,2 '-difunctional biaryl
ID PALOMID 529; WEAK COORDINATION; DIRECTING GROUPS; BOND ACTIVATION;
   RHODIUM; RUTHENIUM; INHIBITOR; ARYLATION; DENSITY; COMPLEXES
AB We herein illustrate the dual chelation-assisted strategy for a Ru(II)-catalyzed oxidative ortho-C-H/C-H cross-coupling of phenols with (hetero)aromatic amides with the aid of Zn(OTf)(2), which enables to rapidly assemble a rich library of 2'-hydroxybiphenyl-2-carboxylic acid derivatives. This protocol features broad substrate scope, excellent functional group tolerance, air as the terminal oxidant, low molar ratio of coupling partners, and scale-up synthesis. Particularly, this methodology is tolerant of more complex natural product derivatives, thus providing an opportunity for late-stage functionalization. This protocol is also used as a key step for the concise synthesis of Palomid 529, a drug in development for the treatment of glioblastoma and neovascular age-related macular degeneration. With a combination of experimental and theoretical methods, we get more insight into the essential issues of strategy determining the reaction process. The stronger coordinating ability of 2-aryloxypyridine and the less steric hindrance of amide are pivotal to the high chemoselectivity of cross-coupling over homocoupling. The first C-H bond activation step takes place at the amide substrate, and the following C-H bond activation at 2-aryloxypyridine is involved in the rate-determined step.
C1 [Zhang, Luoqiang; Zhang, Yuming; Yang, Yudong; Wu, Yimin; Ma, Weixin; You, Jingsong] Sichuan Univ, Key Lab Green Chem & Technol, Minist Educ, Coll Chem, 29 Wangjiang Rd, Chengdu 610064, Peoples R China.
   [Zhu, Lei; Lan, Yu] Chongqing Univ, Sch Chem & Chem Engn, Chongqing 400030, Peoples R China.
C3 Sichuan University; Chongqing University
RP You, JS (通讯作者)，Sichuan Univ, Key Lab Green Chem & Technol, Minist Educ, Coll Chem, 29 Wangjiang Rd, Chengdu 610064, Peoples R China.; Lan, Y (通讯作者)，Chongqing Univ, Sch Chem & Chem Engn, Chongqing 400030, Peoples R China.
EM jsyou@scu.edu.cn; lanyu@cqu.edu.cn
RI Yang, Yudong/R-3833-2016; Lan, Yu/A-8146-2016
OI Yang, Yudong/0000-0002-7142-2249; Lan, Yu/0000-0002-2328-0020; Zhu,
   Lei/0000-0002-7870-8469
FU National NSF of China [21432005, 21772020]; Comprehensive Training
   Platform of Specialized Laboratory, College of Chemistry, Sichuan
   University
FX The authors acknowledge the financial support from National NSF of China
   (Nos 21432005 and 21772020) and the Comprehensive Training Platform of
   Specialized Laboratory, College of Chemistry, Sichuan University.
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NR 59
TC 27
Z9 28
U1 0
U2 60
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 2155-5435
J9 ACS CATAL
JI ACS Catal.
PD SEP
PY 2018
VL 8
IS 9
BP 8324
EP 8335
DI 10.1021/acscatal.8b02816
PG 23
WC Chemistry, Physical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry
GA GT2XY
UT WOS:000444364800062
DA 2022-11-30
ER

PT J
AU Karamali, F
   Esfahani, MHN
   Taleahmad, S
   Satarian, L
   Baharvand, H
AF Karamali, Fereshteh
   Esfahani, Mohammad-Hossein Nasr
   Taleahmad, Sara
   Satarian, Leila
   Baharvand, Hossein
TI Stem cells from apical papilla promote differentiation of human
   pluripotent stem cells towards retinal cells
SO DIFFERENTIATION
LA English
DT Article
DE Co-culture; Human pluripotent stem cell; Retinal pigment epithelium;
   Retinal progenitor cells; Stem cell from apical papilla; Stromal
   cell-derived inducing activity
ID DOPAMINERGIC-NEURONS; PIGMENTED EPITHELIUM; MACULAR DEGENERATION; EYE
   DEVELOPMENT; IN-VITRO; ES CELLS; GENERATION; MORPHOGENESIS; INDUCTION;
   SECRETOME
AB Recently, we have found that human stem cells from apical papilla (SCAP) show a stromal cell-derived inducing activity (SDIA). To examine SDIA competence for retinal cells differentiation, we co-cultured SCAP with human pluripotent stem cells (hPSCs). In comparison with Matrigel-cultured hPSCs, SCAP significantly induces hPSCs to differentiate into rostral neural cells as demonstrated by upregulation of O7X2 and PAX6 and down-regulation of EN1, HOXB4 and HOXCS. Furthermore, the differentiated cells on SCAP significantly expressed eye-field markers, RAX, PAX6, LHX2 and SIX3 and showed five folds pigmented colonies. The generated hPSC-retinal pigmented epithelium (RPE) was hexagonal and highly expressed related markers, ZO-1, RPE65, BEST, CRALBP and MITF. They were able to phagocytose latex beads. Moreover, the assessment of the isolated neural tube-like structures on SCAP showed the expression of retinal progenitor cells (RPCs)-SIX3, RAX, and PAX6. SCAP highly expressed DKK3 and SFRP2, Wnt inhibitor factors and their target genes, Cyclin al and c-Myc were down-regulated significantly on SCAP. These results showed SCAP promoted the differentiation of hPSCs into retinal cells (RPE and RPCs) possibly through inhibition of Wnt signaling pathway. This simple and efficient approach provides human RPE generation for developing therapies for diseases such as age-related macular degeneration.
C1 [Karamali, Fereshteh; Esfahani, Mohammad-Hossein Nasr] ACECR, Royan Inst Biotechnol, Cell Sci Res Ctr, Dept Cellular Biotechnol, Esfahan, Iran.
   [Karamali, Fereshteh; Baharvand, Hossein] Univ Sci & Culture, Dept Dev Biol, Tehran, Iran.
   [Taleahmad, Sara; Satarian, Leila; Baharvand, Hossein] ACECR, Cell Sci Res Ctr, Royan Inst Stem Cell Biol & Technol, Dept Stem Cells & Dev Biol, Tehran, Iran.
C3 Academic Center for Education, Culture & Research (ACECR); Academic
   Center for Education, Culture & Research (ACECR)
RP Esfahani, MHN (通讯作者)，ACECR, Royan Inst Biotechnol, Cell Sci Res Ctr, Dept Cellular Biotechnol, Esfahan, Iran.; Baharvand, H (通讯作者)，ACECR, Cell Sci Res Ctr, Royan Inst Stem Cell Biol & Technol, Dept Stem Cells & Dev Biol, Tehran, Iran.
EM mh.nasr-esfahani@royaninstitute.org; baharvand@royaninstitute.org
RI Nasr-Esfahani, Mohammad Hossein/AAN-2577-2020; Satarian,
   Leila/M-3835-2017; Taleahmad, Sara/ABC-5881-2021; ,
   Nasr-Esfahani/AAR-2434-2021
OI Nasr-Esfahani, Mohammad Hossein/0000-0003-1983-3435; Satarian,
   Leila/0000-0002-5068-5031; Taleahmad, Sara/0000-0003-4666-1907; 
FU Royan Institute; Iranian Council of Stem Cell Research and Technology;
   Iran National Science Foundation (INSF); Iran Science Elites Federation
FX This work was supported by grants from Royan Institute, the Iranian
   Council of Stem Cell Research and Technology, Iran National Science
   Foundation (INSF), and Iran Science Elites Federation to H. B and
   another grant from Royan Institute to M. H. N. E. We are grateful to
   Fatemeh Ejeian and Khadijeh Karbalae for their helpful suggestions.
CR Baharvand H, 2006, DEV GROWTH DIFFER, V48, P117, DOI 10.1111/j.1440-169x.2006.00851.x
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NR 35
TC 13
Z9 13
U1 1
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0301-4681
EI 1432-0436
J9 DIFFERENTIATION
JI Differentiation
PD MAY-JUN
PY 2018
VL 101
BP 8
EP 15
DI 10.1016/j.diff.2018.02.003
PG 8
WC Cell Biology; Developmental Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Developmental Biology
GA GI6IQ
UT WOS:000434473400002
PM 29574166
DA 2022-11-30
ER

PT J
AU Yamawaki, S
   Naitoh, M
   Kubota, H
   Aya, R
   Katayama, Y
   Ishiko, T
   Tamura, T
   Yoshikawa, K
   Enoshiri, T
   Ikeda, M
   Suzuki, S
AF Yamawaki, Satoko
   Naitoh, Motoko
   Kubota, Hiroshi
   Aya, Rino
   Katayama, Yasuhiro
   Ishiko, Toshihiro
   Tamura, Taku
   Yoshikawa, Katsuhiro
   Enoshiri, Tatsuki
   Ikeda, Mika
   Suzuki, Shigehiko
TI HtrA1 Is Specifically Up-Regulated in Active Keloid Lesions and
   Stimulates Keloid Development
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE keloids; fibroproliferative disorder; HtrA1; inflammation
ID BETA-BINDING-PROTEIN; GROWTH-FACTOR-BETA; TGF-BETA;
   EXTRACELLULAR-MATRIX; ADJUVANT IRRADIATION; HYPERTROPHIC SCARS; SURGICAL
   EXCISION; GENE-EXPRESSION; SERINE-PROTEASE; ACTIVATION
AB Keloids occur after failure of the wound healing process; inflammation persists, and various treatments are ineffective. Keloid pathogenesis is still unclear. We have previously analysed the gene expression profiles in keloid tissue and found that HtrA1 was markedly up-regulated in the keloid lesions. HtrA1 is a serine protease suggested to play a role in the pathogenesis of various diseases, including age-related macular degeneration and osteoarthritis, by modulating extracellular matrix or cell surface proteins. We analysed HtrA1 localization and its role in keloid pathogenesis. Thirty keloid patients and twelve unrelated patients were enrolled for in situ hybridization, immunohistochemical, western blot, and cell proliferation analyses. Fibroblast-like cells expressed more HtrA1 in active keloid lesions than in surrounding lesions. The proportion of HtrA1-positive cells in keloids was significantly higher than that in normal skin, and HtrA1 protein was up-regulated relative to normal skin. Silencing HtrA1 gene expression significantly suppressed cell proliferation. HtrA1 was highly expressed in keloid tissues, and the suppression of the HtrA1 gene inhibited the proliferation of keloid-derived fibroblasts. HtrA1 may promote keloid development by accelerating cell proliferation and remodelling keloid-specific extracellular matrix or cell surface molecules. HtrA1 is suggested to have an important role in keloid pathogenesis.
C1 [Yamawaki, Satoko] Japanese Red Cross Fukui Hosp, Dept Plast & Reconstruct Surg, 2-4-1 Tsukimi, Fukui, Fukui 9188501, Japan.
   [Naitoh, Motoko; Aya, Rino; Katayama, Yasuhiro; Enoshiri, Tatsuki; Suzuki, Shigehiko] Kyoto Univ, Grad Sch Med, Dept Plast & Reconstruct Surg, Sakyo Ku, 54 Kawahara Cho, Kyoto 6068507, Japan.
   [Kubota, Hiroshi; Tamura, Taku] Akita Univ, Dept Life Sci, Fac Engn Sci, 1-1 Tegata Gakuenmachi, Akita 0108502, Japan.
   [Ishiko, Toshihiro] Japanese Red Cross Otsu Hosp, Dept Plast & Reconstruct Surg, 1-1-35 Nagara, Otsu, Shiga 5208511, Japan.
   [Yoshikawa, Katsuhiro] Shiga Med Ctr Adults, Dept Plast & Reconstruct Surg, 5-4-30 Moriyama, Moriyama, Shiga 5248524, Japan.
   [Ikeda, Mika] Kobe City Med Ctr Gen Hosp, Dept Plast & Reconstruct Surg, Cyuou Ku, Minatojima Minami Machi, Kobe, Hyogo 6500047, Japan.
C3 Kyoto University; Akita University; Kobe City Medical Center General
   Hospital
RP Naitoh, M (通讯作者)，Kyoto Univ, Grad Sch Med, Dept Plast & Reconstruct Surg, Sakyo Ku, 54 Kawahara Cho, Kyoto 6068507, Japan.
EM satokoy@kuhp.kyoto-u.ac.jp; mnaitoh@kuhp.kyoto-u.ac.jp;
   hkubota@gipc.akita-u.ac.jp; rinok@kuhp.kyoto-u.ac.jp;
   hemim@kuhp.kyoto-u.ac.jp; ishiko@otsu.jrc.or.jp;
   taku@gipc.akita-u.ac.jp; khiro@kuhp.kyoto-u.ac.jp;
   enotatsu@kuhp.kyoto-u.ac.jp; mikaring@crux.ocn.ne.jp;
   ssuzuk@kuhp.kyoto-u.ac.jp
RI Yoshikawa, Katsuhiro/X-1186-2019
OI Tamura, Taku/0000-0001-6074-9273
FU JSPS KAKENHI [15H05003, 23592646]
FX This work was supported by JSPS KAKENHI Grant Number 23592646 and
   15H05003.
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NR 27
TC 5
Z9 5
U1 1
U2 11
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 MAY
PY 2018
VL 19
IS 5
AR 1275
DI 10.3390/ijms19051275
PG 12
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA GJ4BO
UT WOS:000435297000011
PM 29695130
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Hytti, M
   Andjelic, S
   Josifovska, N
   Piippo, N
   Korhonen, E
   Hawlina, M
   Kaarniranta, K
   Nevalainen, TJ
   Petrovski, G
   Parkkari, T
   Kauppinen, A
AF Hytti, M.
   Andjelic, S.
   Josifovska, N.
   Piippo, N.
   Korhonen, E.
   Hawlina, M.
   Kaarniranta, K.
   Nevalainen, T. J.
   Petrovski, G.
   Parkkari, T.
   Kauppinen, A.
TI CB2 receptor activation causes an ERK1/2-dependent inflammatory response
   in human RPE cells
SO SCIENTIFIC REPORTS
LA English
DT Article
ID CANNABINOID RECEPTORS; MACULAR DEGENERATION; IN-VIVO; SECRETION;
   CYTOTOXICITY; AUTOPHAGY; DISEASE
AB A chronic low-level inflammation contributes to the pathogenesis of age-related macular degeneration (AMD), the most common cause of blindness in the elderly in Western countries. The loss of central vision results from attenuated maintenance of photoreceptors due to the degeneration of retinal pigment epithelium (RPE) cells beneath the photoreceptor layer. It has been proposed that pathologic inflammation initiated in RPE cells could be regulated by the activation of type 2 cannabinoid receptors (CB2). Here, we have analysed the effect of CB2 activation on cellular survival and inflammation in human RPE cells. RPE cells were treated with the selective CB2 agonist JWH-133 in the presence or absence of the oxidative stressor 4-hydroxynonenal. Thereafter, cellular viability as well as the release of pro-inflammatory cytokines and potential underlying signalling pathways were analysed. Our results show that JWH-133 led to increased intracellular Ca2+ levels, suggesting that RPE cells are capable of responding to a CB2 agonist. JWH-133 could not prevent oxidative stress-induced cell death. Instead, 10 mu M JWH-133 increased cell death and the release of proinflammatory cytokines in an ERK1/2-dependent manner. In contrast to previous findings, CB2 activation increased, rather than reduced inflammation in RPE cells.
C1 [Hytti, M.; Piippo, N.; Korhonen, E.; Nevalainen, T. J.; Parkkari, T.; Kauppinen, A.] Univ Eastern Finland, Sch Pharm, Kuopio, Finland.
   [Hytti, M.; Piippo, N.; Korhonen, E.; Kaarniranta, K.] Univ Eastern Finland, Sch Med, Dept Ophthalmol, Kuopio, Finland.
   [Andjelic, S.; Hawlina, M.] Univ Med Ctr, Eye Hosp, Ljubljana, Slovenia.
   [Josifovska, N.; Petrovski, G.] Univ Szeged, Fac Med, Dept Ophthalmol, Stem Cells & Eye Res Lab, Szeged, Hungary.
   [Kaarniranta, K.] Kuopio Univ Hosp, Dept Ophthalmol, Kuopio, Finland.
   [Petrovski, G.] Univ Oslo, Oslo Univ Hosp, Dept Ophthalmol, Ctr Eye Res, Oslo, Norway.
   [Petrovski, G.] Univ Oslo, Oslo Univ Hosp, Norwegian Ctr Stem Cell Res, Oslo, Norway.
C3 University of Eastern Finland; University of Eastern Finland; University
   Medical Centre Ljubljana; Szeged University; Kuopio University Hospital;
   University of Eastern Finland; University of Oslo; University of Oslo
RP Hytti, M (通讯作者)，Univ Eastern Finland, Sch Pharm, Kuopio, Finland.; Hytti, M (通讯作者)，Univ Eastern Finland, Sch Med, Dept Ophthalmol, Kuopio, Finland.
EM maria.hytti@uef.fi
RI Hytti, Maria/AAE-4016-2019; Hawlina, Marko/AAZ-8084-2020
OI Hytti, Maria/0000-0003-2150-6847; Petrovski, Goran/0000-0003-2905-9252;
   Josifovska, Natasha/0000-0002-3898-9729; Korhonen,
   Eveliina/0000-0002-5360-7258
FU Finnish Cultural Foundation; Hilda and Evald Nissi Foundation; Academy
   of Finland (Health Research Council) [297267, 307341]; Paivikki and
   Sakari Sohlberg Foundation; Emil Aaltonen Foundation; Orion Research
   Foundation; Sokeain ystavat ry; National Brain Research Program
   [KTIA_NAP_13-A_III/9]; European Union [GINOP-2.3.2-15-2016-00006];
   European Regional Development Fund [GINOP-2.3.2-15-2016-00006]
FX Parts of this research have been shown previously at the European Vision
   and Eye Research Conference 2014 in Nice, France. This research was
   supported by grants from the Finnish Cultural Foundation - North Savo
   Regional Fund, the Hilda and Evald Nissi Foundation, the Academy of
   Finland (Health Research Council projects 297267 and 307341), Sokeain
   ystavat ry, the Paivikki and Sakari Sohlberg Foundation, the Emil
   Aaltonen Foundation and the Orion Research Foundation. The work of G.P.
   and N.J. has been supported by the National Brain Research Program
   (KTIA_NAP_13-A_III/9) and the GINOP-2.3.2-15-2016-00006 project
   (co-financed by the European Union and the European Regional Development
   Fund). We thank Dr. Ewen MacDonald for his help in revising the language
   of the manuscript, Res. Dir. Emeritus Antero Salminen for his valuable
   collaboration, discussions, and critical review of the manuscript, and
   Jenna Sahamies and Dora Szabo for their assistance with laboratory work.
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NR 42
TC 10
Z9 10
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD NOV 23
PY 2017
VL 7
AR 16169
DI 10.1038/s41598-017-16524-w
PG 9
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA FN6MS
UT WOS:000416129500004
PM 29170454
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Hamm, C
   Shechtman, D
   Reynolds, S
AF Hamm, Casey
   Shechtman, Diana
   Reynolds, Sherrol
TI A deeper look at torpedo maculopathy
SO CLINICAL AND EXPERIMENTAL OPTOMETRY
LA English
DT Review
DE OCTA; optical coherence tomography; torpedo maculopathy
ID SPECTRUM
AB BackgroundTorpedo maculopathy is a rare, congenital maculopathy classically diagnosed funduscopically as a torpedo-shaped' lesion located temporal to the fovea. This case describes a torpedo maculopathy with non-classic optical coherence tomographic (OCT) findings and collaborative OCT angiographic (OCTA) findings.
   Case reportA 60-year-old Caucasian woman presented with a history of longstanding distortion and paracentral scotoma of the right eye. She had a positive family history of age-related macular degeneration. Visual acuity was 6/6 in each eye. Dilated fundus examination revealed a torpedo-shaped lesion in the right eye with a hypo-pigmented head pointing toward the fovea and a hyper-pigmented tail end. OCT imaging of the macula of the right eye revealed a subretinal cleft space with underlying thinning of the retinal pigment epithelium, increased choroidal reflectivity, as well as retinal pigment epithelial and choroidal excavation. OCTA choriocapillaris segmentation showed a hypo-reflective area associated with the lesion, adjacent to hyper-reflectivity. The patient was diagnosed with torpedo maculopathy of the right eye.
   Conclusions OCT and OCTA imaging have been instrumental in developing a deeper understanding of many maculopathies, allowing for accurate diagnosis of macular conditions. Although the aetiology remains unclear, these imaging devices may provide further insight into the lesion in torpedo maculopathy.
C1 [Hamm, Casey] Univ Missouri, Coll Optometry, St Louis, MO 63121 USA.
   [Shechtman, Diana; Reynolds, Sherrol] Nova Southeastern Univ, Coll Optometry, Ft Lauderdale, FL 33314 USA.
C3 University of Missouri System; University of Missouri Saint Louis; Nova
   Southeastern University
RP Hamm, C (通讯作者)，Univ Missouri, Coll Optometry, St Louis, MO 63121 USA.
EM hammcm@umsl.edu
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NR 15
TC 13
Z9 14
U1 0
U2 0
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0816-4622
EI 1444-0938
J9 CLIN EXP OPTOM
JI Clin. Exp. Optom.
PD NOV
PY 2017
VL 100
IS 6
BP 563
EP 568
DI 10.1111/cxo.12540
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FM4FI
UT WOS:000414968100003
PM 28436087
OA Bronze
DA 2022-11-30
ER

PT J
AU Tuo, SH
   Zhang, JY
   Yuan, XG
   He, ZZ
   Liu, YJ
   Liu, ZW
AF Tuo, Shouheng
   Zhang, Junying
   Yuan, Xiguo
   He, Zongzhen
   Liu, Yajun
   Liu, Zhaowen
TI Niche harmony search algorithm for detecting complex disease associated
   high-order SNP combinations
SO SCIENTIFIC REPORTS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; EPISTATIC INTERACTIONS; OPTIMIZATION ALGORITHM;
   FACTOR-H; GENE; INPP4B
AB Genome-wide association study is especially challenging in detecting high-order disease-causing models due to model diversity, possible low or even no marginal effect of the model, and extraordinary search and computations. In this paper, we propose a niche harmony search algorithm where joint entropy is utilized as a heuristic factor to guide the search for low or no marginal effect model, and two computationally lightweight scores are selected to evaluate and adapt to diverse of disease models. In order to obtain all possible suspected pathogenic models, niche technique merges with HS, which serves as a taboo region to avoid HS trapping into local search. From the resultant set of candidate SNP-combinations, we use G-test statistic for testing true positives. Experiments were performed on twenty typical simulation datasets in which 12 models are with marginal effect and eight ones are with no marginal effect. Our results indicate that the proposed algorithm has very high detection power for searching suspected disease models in the first stage and it is superior to some typical existing approaches in both detection power and CPU runtime for all these datasets. Application to age-related macular degeneration (AMD) demonstrates our method is promising in detecting high-order disease-causing models.
C1 [Tuo, Shouheng; Zhang, Junying; Yuan, Xiguo; He, Zongzhen; Liu, Yajun; Liu, Zhaowen] Xidian Univ, Sch Comp Sci & Technol, Xian 710071, Shaanxi, Peoples R China.
   [Tuo, Shouheng] Shaanxi Univ Technol, Sch Math & Comp Sci, Hanzhong 723000, Peoples R China.
C3 Xidian University; Shaanxi University of Technology
RP Tuo, SH; Zhang, JY (通讯作者)，Xidian Univ, Sch Comp Sci & Technol, Xian 710071, Shaanxi, Peoples R China.; Tuo, SH (通讯作者)，Shaanxi Univ Technol, Sch Math & Comp Sci, Hanzhong 723000, Peoples R China.
EM tuo_sh@126.com; jyzhang_xidian@qq.com
RI tuo, shouheng/AAC-1997-2019; Liu, Zhaowen/AAM-6710-2021
OI ShouHeng, Tuo/0000-0002-6696-0085
FU Natural Science Foundation of China [61571341, 61201312, 91530113,
   11401357]; Research Fund for the Doctoral Program of Higher Education of
   China [20130203110017]; Fundamental Research Funds for the Central
   Universities of China [BDY171416, JB140306]; Natural Science Foundation
   of Shaanxi Province in China [2015JM6275]; Free exploration projects for
   basic research-related expenses
FX This work was supported by the Natural Science Foundation of China under
   Grants 61571341, 61201312, 91530113 and 11401357, Research Fund for the
   Doctoral Program of Higher Education of China (No. 20130203110017), the
   Fundamental Research Funds for the Central Universities of China (Nos
   BDY171416 and JB140306), the Natural Science Foundation of Shaanxi
   Province in China (2015JM6275), Free exploration projects for 2017 basic
   research-related expenses.
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NR 63
TC 28
Z9 28
U1 0
U2 15
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 SEP 14
PY 2017
VL 7
AR 11529
DI 10.1038/s41598-017-11064-9
PG 18
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA FG9DM
UT WOS:000410739000027
PM 28912584
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Decembrini, S
   Martin, C
   Sennlaub, F
   Chemtob, S
   Bie, M
   Samardzija, M
   Moulin, A
   Behar-Cohen, F
   Arsenijevic, Y
AF Decembrini, Sarah
   Martin, Catherine
   Sennlaub, Florian
   Chemtob, Sylvain
   Bie, Martin
   Samardzija, Marijana
   Moulin, Alexandre
   Behar-Cohen, Francine
   Arsenijevic, Yvan
TI Cone Genesis Tracing by the Chrnb4-EGFP Mouse Line: Evidences of
   Cellular Material Fusion after Cone Precursor Transplantation
SO MOLECULAR THERAPY
LA English
DT Article
ID ROD PHOTORECEPTOR DEVELOPMENT; RAT RETINA; PROTEIN EXPRESSION; REPORTER
   MOUSE; CELLS; DEGENERATION; PROGENITOR; PROLIFERATION; FATE; SURVIVAL
AB The cone function is essential to mediate high visual acuity, color vision, and daylight vision. Inherited cone dystrophies and age-related macular degeneration affect a substantial percentage of the world population. To identify and isolate the most competent cells for transplantation and integration into the retina, cone tracing during development would be an important added value. To that aim, the Chrnb4-EGFP mouse line was characterized throughout retinogenesis. It revealed a sub population of early retinal progenitors expressing the reporter gene that is progressively restricted to mature cones during retina development. The presence of the native CHRNB4 protein was confirmed in EGFP-positive cells, and it presents a similar pattern in the human retina. Sub-retinal transplantations of distinct subpopulations of Chrnb4-EGFP-expressing cells revealed the embryonic day 15.5 high-EGFP population the most efficient cells to interact with host retinas to provoke the appearance of EGFP-positive cones in the photoreceptor layer. Importantly, transplantations into the DsRed retinas revealed material exchanges between donor and host retinas, as >80% of transplanted EGFP-positive cones also were DsRed positive. Whether this cell material fusion is of significant therapeutic advantage requires further thorough investigations. The Chrnb4-EGFP mouse line definitely opens new research perspectives in cone genesis and retina repair.
C1 [Decembrini, Sarah; Martin, Catherine; Arsenijevic, Yvan] Univ Lausanne, Hop Ophtalm Jules Gonin, Fdn Asile Aveugles, Dept Ophthalmol,Unit Retinal Degenerat & Regenera, CH-1004 Lausanne, Switzerland.
   [Sennlaub, Florian] Univ Paris 06, UPMC, INSERM, Sorbonne Univ,UMRS U968 968,Inst Vis, F-75012 Paris, France.
   [Chemtob, Sylvain] Hop Ste, Justine Res Ctr, Dept Pediat, Montreal, PQ H3T 1C5, Canada.
   [Chemtob, Sylvain] Hop Ste, Justine Res Ctr, Dept Ophthalmol & Pharmacol, Montreal, PQ H3T 1C5, Canada.
   [Bie, Martin] Ludwig Maximilians Univ Munchen, Ctr Drug Res, CIPSM, Dept Pharm, D-81377 Munich, Germany.
   [Samardzija, Marijana] Univ Zurich, Dept Ophthalmol, Lab Retinal Cell Biol, CH-8952 Schlieren, Switzerland.
   [Moulin, Alexandre] Univ Lausanne, Hop Ophtalm Jules Gonin, Dept Ophthalmol, Pathol Lab, Fondat Asile Ave, CH-1004 Lausanne, Switzerland.
   [Behar-Cohen, Francine] Univ Lausanne, Hop Ophtalm Jules Gonin, Dept Ophthalmol, Fondat Asile Ave, CH-1004 Lausanne, Switzerland.
C3 University of Lausanne; Institut National de la Sante et de la Recherche
   Medicale (Inserm); UDICE-French Research Universities; Sorbonne
   Universite; University of Munich; University of Lausanne; University of
   Lausanne
RP Arsenijevic, Y (通讯作者)，Univ Lausanne, Hop Ophtalm Jules Gonin, Fdn Asile Aveugles, Dept Ophthalmol,Unit Retinal Degenerat & Regenera, CH-1004 Lausanne, Switzerland.
EM yvan.arsenijevic@fa2.ch
RI Sennlaub, Florian/F-2756-2017; Samardzija, Marijana/B-9245-2008
OI Sennlaub, Florian/0000-0003-4412-1341; Samardzija,
   Marijana/0000-0003-0991-4653; Arsenijevic, Yvan/0000-0001-6960-1291
FU Fondation Provisu; Bayer GOAP program; Novartis Foundation; Fondation
   asile des aveugles; Fondation Open Eyes; Foundation Bertarelli
FX We thank the URDR team members of the Jules-Gonin eye hospital for
   discussion on the work: in particular, Amelie Clement, Florian Udry, and
   Roger Moser for their technical support. We are also thankful to Botond
   Roska at the Friedrich Mischer Institute for providing the Chrnb4-EGFP
   mice, Cathrin Brisken at the EPFL for providing the DsRed mice, for the
   technical assistance provided by the FAGS sorting facility at the Ludwig
   Cancer Research Institute and at the CHUV in Lausanne, for the technical
   assistance of the confocal facility at the EPFL in Lausanne, and to our
   technician Dana Wanner. This work has been supported by the Fondation
   Provisu, the Bayer GOAP program, the Novartis Foundation, the Fondation
   asile des aveugles, the Fondation Open Eyes, and the Foundation
   Bertarelli.
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NR 56
TC 47
Z9 49
U1 0
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAR 1
PY 2017
VL 25
IS 3
BP 634
EP 653
DI 10.1016/j.ymthe.2016.12.015
PG 20
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 EO4AF
UT WOS:000396635500009
PM 28143742
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Zhang, XY
   Ng, TK
   Brelen, ME
   Wu, D
   Wang, JX
   Chan, KP
   Yung, JSY
   Cao, D
   Wang, YM
   Zhang, SD
   Chan, SO
   Pang, CP
AF Zhang, Xiao-Yu
   Ng, Tsz Kin
   Brelen, Marten Erik
   Wu, Di
   Wang, Jian Xiong
   Chan, Kwok Ping
   Yung, Jasmine Sum Yee
   Cao, Di
   Wang, Yumeng
   Zhang, Shaodan
   Chan, Sun On
   Pang, Chi Pui
TI Continuous exposure to non-lethal doses of sodium iodate induces retinal
   pigment epithelial cell dysfunction
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MACULAR DEGENERATION; OXIDATIVE STRESS; RPE CELLS; ARPE-19 CELLS;
   STEM-CELLS; EXPRESSION; AUTOPHAGY; MECHANISM; SMOKING; MICE
AB Age-related macular degeneration (AMD), characterized by progressive degeneration of retinal pigment epithelium (RPE), is the major cause of irreversible blindness and visual impairment in elderly population. We previously established a RPE degeneration model using an acute high dose sodium iodate to induce oxidative stress. Here we report findings on a prolonged treatment of low doses of sodium iodate on human RPE cells (ARPE-19). RPE cells were treated continuously with low doses (2-10 mM) of sodium iodate for 5 days. Low doses (2-5 mM) of sodium iodate did not reduce RPE cell viability, which is contrasting to cell apoptosis in 10 mM treatment. These low doses are sufficient to retard RPE cell migration and reduced expression of cell junction protein ZO-1. Phagocytotic activity of RPE cells was attenuated by sodium iodate dose-dependently. Sodium iodate also increased expression of FGF-2, but suppressed expression of IL-8, PDGF, TIMP-2 and VEGF. Furthermore, HTRA1 and epithelial-to-mesenchymal transition marker proteins were downregulated, whereas PERK and LC3B-II proteins were upregulated after sodium iodate treatment. These results suggested that prolonged exposure to non-lethal doses of oxidative stress induces RPE cell dysfunctions that resemble conditions in AMD. This model can be used for future drug/treatment investigation on AMD.
C1 [Zhang, Xiao-Yu; Ng, Tsz Kin; Brelen, Marten Erik; Wang, Jian Xiong; Chan, Kwok Ping; Yung, Jasmine Sum Yee; Cao, Di; Wang, Yumeng; Pang, Chi Pui] Dept Ophthalmol & Visual Sci, Hong Kong, Hong Kong, Peoples R China.
   [Zhang, Xiao-Yu; Ng, Tsz Kin; Brelen, Marten Erik; Wang, Jian Xiong; Chan, Kwok Ping; Yung, Jasmine Sum Yee; Cao, Di; Wang, Yumeng; Pang, Chi Pui] Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China.
   [Zhang, Xiao-Yu; Wu, Di; Zhang, Shaodan] Fourth Peoples Hosp Shenyang, Dept Ophthalmol, Shenyang, Peoples R China.
   [Zhang, Xiao-Yu; Wu, Di; Zhang, Shaodan] Shenyang Key Lab Ophthalmol, Shenyang, Peoples R China.
   [Chan, Sun On] Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China.
C3 Chinese University of Hong Kong; Chinese University of Hong Kong
RP Ng, TK (通讯作者)，Dept Ophthalmol & Visual Sci, Hong Kong, Hong Kong, Peoples R China.; Ng, TK (通讯作者)，Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China.
EM micntk@hotmail.com
RI Brelen, Marten E./D-1133-2016; Chan, Sun-On/R-6547-2018; Chan, Kwok
   Ping/E-6044-2016; Ng, Tsz Kin/I-8061-2014
OI Chan, Sun-On/0000-0002-3221-3786; Chan, Kwok Ping/0000-0003-2416-1995;
   Ng, Tsz Kin/0000-0001-7863-7229; Wang, Yumeng/0000-0002-2282-0814
FU Health and Medical Research Fund [12130791]; Research Grant Council
   General Research Fund [CUHK14113815]
FX We are grateful to Ms. Yolanda W.Y. Yip and Ms. Pancy O.S. Tam for the
   routine laboratory management and maintenance. This work was supported
   by the Health and Medical Research Fund (project number: 12130791 to
   T.K.N.), and the Research Grant Council General Research Fund (project
   number: CUHK14113815 to S.O.C.).
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NR 44
TC 21
Z9 21
U1 2
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD NOV 16
PY 2016
VL 6
AR 37279
DI 10.1038/srep37279
PG 13
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA EC4ES
UT WOS:000388079700001
PM 27849035
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Menard, C
   Rezende, FA
   Miloudi, K
   Wilson, A
   Tetreault, N
   Hardy, P
   SanGiovanni, JP
   De Guire, V
   Sapieha, P
AF Menard, Catherine
   Rezende, Flavio A.
   Miloudi, Khalil
   Wilson, Ariel
   Tetreault, Nicolas
   Hardy, Pierre
   SanGiovanni, John Paul
   De Guire, Vincent
   Sapieha, Przemyslaw
TI MicroRNA signatures in vitreous humour and plasma of patients with
   exudative AMD
SO ONCOTARGET
LA English
DT Article
DE age-related macular degeneration; AMD; microRNAs; miRNA; biomarkers;
   Gerotarget
ID MACULAR DEGENERATION; CELLS; BIOMARKERS; INTERLEUKIN-1-BETA;
   PROLIFERATION; EXPRESSION; RESISTANCE; DELIVERY; MIRNAS; CANCER
AB Age-related macular degeneration (AMD) is a leading cause of blindness worldwide affecting individuals over the age of 50. The neovascular form (NV AMD) is characterized by choroidal neovascularization (CNV) and responsible for the majority of central vision impairment. Using non-biased microRNA arrays and individual TaqMan qPCRs, we profiled miRNAs in the vitreous humour and plasma of patients with NV AMD. We identified a disease-associated increase in miR-146a and a decrease in miR-106b and miR-152 in the vitreous humour which was reproducible in plasma. Moreover, miR-146a/miR-106b ratios discriminated patients with NV AMD with an area under the Receiver Operating Characteristic curve (ROC AUC) of 0,977 in vitreous humour and 0,915 in plasma suggesting potential for a blood-based diagnostic. Furthermore, using the AMD Gene Consortium (AGC) we mapped a NV AMD-associated SNP (rs1063320) in a binding site for miR-152-3p in the HLA-G gene. The relationship between our detected miRNAs and NV AMD related genes was also investigated using gene sets derived from the Ingenuity Pathway Analysis (IPA). To our knowledge, our study is the first to correlate vitreal and plasma miRNA signatures with NV AMD, highlighting potential future worth as biomarkers and providing insight on NV AMD pathogenesis.
C1 [Menard, Catherine; Tetreault, Nicolas; Sapieha, Przemyslaw] Univ Montreal, Dept Biochem, Hop Maison Neuve Rosemont, Res Ctr, Montreal, PQ H3C 3J7, Canada.
   [Rezende, Flavio A.; Sapieha, Przemyslaw] Univ Montreal, Hop Maison Neuve Rosemont, Res Ctr, Dept Ophthalmol, Montreal, PQ, Canada.
   [Wilson, Ariel] Ecole Polytech, Dept Engn Phys, Laser Proc & Plasmon Lab, Montreal, PQ H3C 3A7, Canada.
   [Miloudi, Khalil; Sapieha, Przemyslaw] McGill Univ, Dept Neurosci, Montreal, PQ, Canada.
   [Hardy, Pierre] Univ Montreal, Dept Pediat, Montreal, PQ H3C 3J7, Canada.
   [Hardy, Pierre] Univ Montreal, Dept Pharmacol, Montreal, PQ H3C 3J7, Canada.
   [SanGiovanni, John Paul] NIAAA, Lab Membrane Biochem & Biophys, Nutr Neurosci Sect, NIH, Bethesda, MD USA.
   [De Guire, Vincent] Hop Maison Neuve Rosemont, Dept Clin Biochem, Quebec City, PQ, Canada.
C3 Universite de Montreal; Universite de Montreal; Universite de Montreal;
   Polytechnique Montreal; McGill University; Universite de Montreal;
   Universite de Montreal; National Institutes of Health (NIH) - USA; NIH
   National Institute on Alcohol Abuse & Alcoholism (NIAAA); Universite de
   Montreal
RP Sapieha, P (通讯作者)，Univ Montreal, Dept Biochem, Hop Maison Neuve Rosemont, Res Ctr, Montreal, PQ H3C 3J7, Canada.; Sapieha, P (通讯作者)，Univ Montreal, Hop Maison Neuve Rosemont, Res Ctr, Dept Ophthalmol, Montreal, PQ, Canada.; Sapieha, P (通讯作者)，McGill Univ, Dept Neurosci, Montreal, PQ, Canada.; De Guire, V (通讯作者)，Hop Maison Neuve Rosemont, Dept Clin Biochem, Quebec City, PQ, Canada.
EM vdeguire.hmr@ssss.gouv.qc.ca; mike.sapieha@umontreal.ca
RI SanGiovanni, John Paul/AAU-3895-2020
FU Foundation Fighting Blindness Canada; Canadian Institutes of Health
   Research [221478]; Natural Sciences and Engineering Research Council of
   Canada [418637]; Fondation HMR; Reseau en Recherche en Sante de la
   Vision du Quebec; Fond en Recherche en Opthalmologie de l'UdeM
FX PS holds a Canada Research Chair in Retinal Cell Biology and The Alcon
   Research Institute Young Investigator Award. This work was supported by
   operating grants to PS from the Foundation Fighting Blindness Canada and
   the Canadian Institutes of Health Research (221478) and Natural Sciences
   and Engineering Research Council of Canada (418637). Additional support
   was obtained from the Fondation HMR, Reseau en Recherche en Sante de la
   Vision du Quebec and the Fond en Recherche en Opthalmologie de l'UdeM.
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NR 53
TC 62
Z9 63
U1 1
U2 4
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 APR 12
PY 2016
VL 7
IS 15
BP 19171
EP 19184
DI 10.18632/oncotarget.8280
PG 14
WC Oncology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Cell Biology
GA DL7ES
UT WOS:000375804000008
PM 27015561
OA Green Accepted, Green Submitted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Falk, MK
   Singh, A
   Faber, C
   Nissen, MH
   Hviid, T
   Sorensen, TL
AF Falk, Mads Kruger
   Singh, Amardeep
   Faber, Carsten
   Nissen, Mogens Holst
   Hviid, Thomas
   Sorensen, Torben Lykke
TI CX3CL1/CX3CR1 and CCL2/CCR2 Chemokine/Chemokine Receptor Complex in
   Patients with AMD
SO PLOS ONE
LA English
DT Article
ID MACULAR DEGENERATION; SUBRETINAL MICROGLIA; RETINAL MICROGLIA;
   ANIMAL-MODEL; T-CELLS; EXPRESSION; PATHOGENESIS; CHEMOKINE;
   ACCUMULATION; MONOCYTES
AB Purpose: The chemokine receptors CX3CR1 and CCR2 have been implicated in the development of age-related macular degeneration (AMD). The evidence is mainly derived from experimental cell studies and murine models of AMD. The purpose of this study was to investigate the association between expression of CX3CR1 and CCR2 on different leukocyte subsets and AMD. Furthermore we measured the plasma levels of ligands CX3CL1 and CCL2.
   Methods: Patients attending our department were asked to participate in the study. The diagnosis of AMD was based on clinical examination and multimodal imaging techniques. Chemokine plasma level and chemokine receptor expression were measured by flow-cytometry.
   Results: A total of 150 participants were included. We found a significantly lower expression of CX3CR1 on CD8(+) T cells in the neovascular AMD group compared to the control group (p=0.04). We found a significant positive correlation between CCR2 and CX3CR1 expression on CD8(+) cells (r=0.727, p=0.0001). We found no difference in plasma levels of CX3CL1 and CCL2 among the groups.
   Conclusions: Our results show a down regulation of CX3CR1 on CD8(+) cells; this correlated to a low expression of CCR2 on CD8(+) cells. Further studies are needed to elucidate the possible role of this cell type in AMD development.
C1 [Falk, Mads Kruger; Singh, Amardeep; Sorensen, Torben Lykke] Univ Copenhagen, Hosp Roskilde, Dept Ophthalmol, Clin Eye Res Unit, Roskilde, Denmark.
   [Falk, Mads Kruger; Singh, Amardeep; Hviid, Thomas; Sorensen, Torben Lykke] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark.
   [Faber, Carsten; Nissen, Mogens Holst] Univ Copenhagen, Fac Hlth Sci, Dept Microbiol Immunol & Int Hlth, Copenhagen, Denmark.
   [Hviid, Thomas] Univ Copenhagen, Hosp Roskilde, Dept Clin Biochem, Ctr Immune Regulat & Reprod Immunol, Roskilde, Denmark.
   [Faber, Carsten] Glostrup Cty Hosp, Dept Ophthalmol, Glostrup, Denmark.
C3 University of Copenhagen; University of Copenhagen; University of
   Copenhagen; University of Copenhagen; University of Copenhagen
RP Falk, MK (通讯作者)，Univ Copenhagen, Hosp Roskilde, Dept Ophthalmol, Clin Eye Res Unit, Roskilde, Denmark.
EM madskrugerfalk@gmail.com
RI Faber, Carsten/N-3210-2019; Faber, Carsten/I-4150-2013; Nissen,
   Mogens/B-4825-2008; Singh, Amardeep/ABI-4544-2020
OI Faber, Carsten/0000-0002-2517-7270; Faber, Carsten/0000-0002-2517-7270;
   Nissen, Mogens/0000-0001-7729-8667; 
FU Danish Eye Health Society (Vaern om Synet); Danish Eye Research
   foundation; Synoptik Foundation; Region Zealand's Research Fund
FX This study was supported by the Danish Eye Health Society (Vaern om
   Synet) - www.vos.dk, the Danish Eye Research foundation -
   www.dkblind.dk, Region Zealand's Research Fund
   -http://www.regionsjaelland.dk/sundhed/forskning/praktisk%20om%20forskni
   ng/sider/den-regionale-forskningsfond.aspx, and the Synoptik Foundation
   http://synoptik-fonden.dk/. The funders had no role in study design,
   data collection and analysis, decision to publish, or preparation of the
   manuscript.
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NR 42
TC 18
Z9 18
U1 1
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 DEC 15
PY 2014
VL 9
IS 12
AR e112473
DI 10.1371/journal.pone.0112473
PG 15
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA AW9WY
UT WOS:000346607100004
PM 25503251
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Aguilar, C
   Castet, E
AF Aguilar, Carlos
   Castet, Eric
TI Gaze-contingent simulation of retinopathy: Some potential pitfalls and
   remedies
SO VISION RESEARCH
LA English
DT Article
DE Age related macular degeneration; Gaze-contingent display; Artificial
   scotoma; Blink; Slow eye movement
ID SMOOTH EYE-MOVEMENTS; ARTIFICIAL VISION; FIXATION STABILITY; MOTION
   PERCEPTION; VISUAL-SEARCH; SCOTOMAS; TIME; SUPPRESSION; STRATEGY;
   DISPLAYS
AB Many important results in visual neuroscience rely on the use of gaze-contingent retinal stabilization techniques. Our work focuses on the important fraction of these studies that is concerned with the retinal stabilization of visual filters that degrade some specific portions of the visual field. For instance, macular scotomas, often induced by age related macular degeneration, can be simulated by continuously displaying a gaze-contingent mask in the center of the visual field. The gaze-contingent rules used in most of these studies imply only a very minimal processing of ocular data. By analyzing the relationship between gaze and scotoma locations for different oculo-motor patterns, we show that such a minimal processing might have adverse perceptual and oculomotor consequences due mainly to two potential problems: (a) a transient blink-induced motion of the scotoma while gaze is static, and (b) the intrusion of post-saccadic slow eye movements. We have developed new gaze-contingent rules to solve these two problems. We have also suggested simple ways of tackling two unrecognized problems that are a potential source of mismatch between gaze and scotoma locations. Overall, the present work should help design, describe and test the paradigms used to simulate retinopathy with gaze-contingent displays. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Aguilar, Carlos; Castet, Eric] Univ Aix Marseille 2, CNRS, Inst Neurosci Cognit Mediterranee, F-13009 Marseille, France.
C3 Centre National de la Recherche Scientifique (CNRS); UDICE-French
   Research Universities; Aix-Marseille Universite
RP Castet, E (通讯作者)，Univ Aix Marseille 2, CNRS, Inst Neurosci Cognit Mediterranee, 31 Chemin Joseph Aiguier, F-13009 Marseille, France.
EM Eric.Castet@incm.cnrs-mrs.fr
FU Essilor International Ph.D. Grant
FX We thank the SR Research team, especially Suganthan Subramaniam, Jiye
   Shen and Sol Simpson, for their constant support concerning programming
   and instrumentation issues. The first author was supported by an Essilor
   International Ph.D. Grant.
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NR 57
TC 44
Z9 44
U1 1
U2 13
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0042-6989
EI 1878-5646
J9 VISION RES
JI Vision Res.
PD MAY 11
PY 2011
VL 51
IS 9
BP 997
EP 1012
DI 10.1016/j.visres.2011.02.010
PG 16
WC Neurosciences; Ophthalmology; Psychology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Ophthalmology; Psychology
GA 764BI
UT WOS:000290603000004
PM 21335024
OA Bronze
DA 2022-11-30
ER

PT J
AU Tolentino, M
AF Tolentino, Michael
TI Systemic and Ocular Safety of Intravitreal Anti-VEGF Therapies for
   Ocular Neovascular Disease
SO SURVEY OF OPHTHALMOLOGY
LA English
DT Review
DE bevacizumab; ocular neovascular diseases; pegaptanib; ranibizumab;
   safety; vascular endothelial growth factor inhibitor
ID ENDOTHELIAL-GROWTH-FACTOR; RETINAL-PIGMENT EPITHELIUM; VERTEPORFIN
   PHOTODYNAMIC THERAPY; BEVACIZUMAB AVASTIN TREATMENT;
   VASCULAR-PERMEABILITY FACTOR; EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION;
   INTRAOCULAR-PRESSURE CHANGES; ISCHEMIC OPTIC NEUROPATHY; NITRIC-OXIDE
   PRODUCTION; UNTREATED FELLOW EYE
AB The treatment of ocular neovascular diseases is being revolutionized by intravitreal therapies targeting vascular endothelial growth factor (VEGF). Two agents are approved for treating neovascular age-related macular degeneration and are being evaluated for other retinal conditions: the RNA aptamer pegaptanib and the monoclonal antibody antigen-binding fragment ranibizumab. Bevacizumab, a related antibody, is being used similarly, although its use is off-label. Pegaptanib selectively binds to a VEGF isoform identified as being especially pathogenic in the eye and spares other isoforms, whereas the other two agents nonselectively bind all VEGF isoforms. Because VEGF is involved in a wide variety of physiologic processes, the ocular and systemic safety of anti-VEGF agents is of paramount concern. I provide an overview of safety data for intravitreal anti-VEGF therapies, focusing primarily on randomized, controlled trials. For pegaptanib, an accumulation of data from pivotal trials and a dedicated systemic safety study have revealed no ocular or systemic safety concerns. For ranibizumab, the principal ocular adverse event detected in clinical trials was a low frequency of ocular inflammation, and systemic adverse events included a slightly elevated risk of nonocular hemorrhage and stroke. Safety data from properly designed randomized controlled trials for bevacizumab are not available. (Surv Ophthalmol 56:95-113, 2011. (C) 2011 Elsevier Inc. All rights reserved.)
C1 Ctr Retina & Macular Dis, Winter Haven, FL 33880 USA.
RP Tolentino, M (通讯作者)，Ctr Retina & Macular Dis, 250 Ave K SW, Winter Haven, FL 33880 USA.
EM Miket@crmd.net
FU Genentech; Eyetech; Novartis; Pfizer; Pfizer Inc; (OSI) Eyetech, Inc.
FX The author receives research funding, is a consultant, and serves on
   speakers bureaus for Genentech, Eyetech, Novartis and Pfizer companies
   whose products are mentioned in this article. Editorial support,
   including development and styling the paper for journal, contribution to
   the literature review and manuscript submission, was provided by Dr.
   Lauren Swenarchuk of Zola Associates and was funded by Pfizer Inc and
   (OSI) Eyetech, Inc.
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NR 248
TC 195
Z9 205
U1 0
U2 24
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 MAR-APR
PY 2011
VL 56
IS 2
BP 95
EP 113
DI 10.1016/j.survophthal.2010.08.006
PG 19
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 731XM
UT WOS:000288143800001
PM 21335144
DA 2022-11-30
ER

PT J
AU Thumann, G
   Stocker, M
   Maltusch, C
   Salz, AK
   Barth, S
   Walter, P
   Johnen, S
AF Thumann, G.
   Stoecker, M.
   Maltusch, C.
   Salz, A. K.
   Barth, S.
   Walter, P.
   Johnen, S.
TI High efficiency non-viral transfection of retinal and iris pigment
   epithelial cells with pigment epithelium-derived factor
SO GENE THERAPY
LA English
DT Article
DE neurodegenerative diseases; age-related macular degeneration;
   nucleofection; iris pigment epithelial cells; PEDF
ID THERAPY RESTORES VISION; MACULAR DEGENERATION; GENE-TRANSFER; MOUSE
   MODEL; TRANSPLANTATION; RPE; TRANSLOCATION; EXPRESSION; SECRETION;
   BEHAVIOR
AB Transplantation of pigment epithelial cells in patients with age-related macular degeneration and Parkinson's disease has the potential to improve functional rehabilitation. Genetic modification of cells before transplantation may allow the delivery of neuroprotective factors to achieve functional improvement. As transplantation of cells modified using viral vectors is complicated by the possible dissemination of viral particles and severe immune reactions, we have explored non-viral methods to insert genetic material in pigment epithelial cells. Using lipofection or nucleofection ARPE-19 cells, freshly isolated and primary retinal and iris pigment epithelial (IPE) cells were transfected with plasmids encoding green fluorescent protein (GFP) and with three plasmids encoding recombinant pigment epithelium-derived factor (PEDF) and GFP. Transfection efficiency was evaluated by fluorescence microscopy and stability of protein expression by immunoblotting. Pigment epithelial cells were successfully transfected with plasmid encoding GFP. Expression of GFP in ARPE-19 was transient, but was observed for up to 1 year in IPE cells. Analysis of pigment epithelial cells transfected with PEDF plasmids revealed that PEDF fusion proteins were successfully expressed and functionally active. In conclusion, efficient transfer of genetic information in pigment epithelial cells can be achieved using non-viral transfection protocols. Gene Therapy (2010) 17, 181-189; doi: 10.1038/gt.2009.124; published online 10 September 2009
C1 [Thumann, G.; Walter, P.] Univ Aachen, Rhein Westfal TH Aachen, Dept Ophthalmol, D-52074 Aachen, Germany.
   [Thumann, G.; Stoecker, M.; Maltusch, C.; Salz, A. K.; Johnen, S.] Univ Aachen, Rhein Westfal TH Aachen, IZKF Biomat, D-52074 Aachen, Germany.
   [Barth, S.] Helmholtz Inst Appl Med Engn, Dept Expt Med & Immunotherapy, Aachen, Germany.
C3 RWTH Aachen University; RWTH Aachen University; Helmholtz Association
RP Thumann, G (通讯作者)，Univ Aachen, Rhein Westfal TH Aachen, Dept Ophthalmol, Pauwelsstr 30, D-52074 Aachen, Germany.
EM GThumann@ukaachen.de
RI Walter, Peter/L-5982-2018; Johnen, Sandra/ABA-9955-2020; Barth,
   Stefan/F-7301-2012
OI Walter, Peter/0000-0001-8745-6593; Johnen, Sandra/0000-0003-0028-2557;
   Barth, Stefan/0000-0001-9589-653X
FU RWTH Aachen University
FX This work was supported by a grant from the Interdisciplinary Center for
   Clinical Research 'Biomat.' within the faculty of Medicine at the RWTH
   Aachen University. The authors thank Angela Bleck (Fraunhofer IME,
   Department of Pharmaceutical Product Development, Forckenbeckstrasse 6,
   52074 Aachen, Germany) for technical assistance and Ria Lindt for
   initial work in this project.
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NR 47
TC 18
Z9 19
U1 1
U2 10
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 FEB
PY 2010
VL 17
IS 2
BP 181
EP 189
DI 10.1038/gt.2009.124
PG 9
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 553WR
UT WOS:000274398000005
PM 19741732
OA Bronze
DA 2022-11-30
ER

PT J
AU Kiss, CG
   Simader, C
   Michels, S
   Schmidt-Erfurth, U
AF Kiss, C. G.
   Simader, C.
   Michels, S.
   Schmidt-Erfurth, U.
TI Combination of verteporfin photodynamic therapy and ranibizumab: effects
   on retinal anatomy, choroidal perfusion and visual function in the
   protect study
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; NEOVASCULARIZATION;
   PEGAPTANIB; EFFICACY; SAFETY
AB Objective: To evaluate verteporfin and same-day ranibizumab on retina, choroid, vasculature, choroidal neovascularisation (CNV) and visual function.
   Methods: Eleven patients with occult or predominantly classic subfoveal CNV secondary to age-related macular degeneration received verteporfin and four monthly intravitreal ranibizumab injections. Eyes were examined using fluorescein angiography (FA) and indocyanine green angiography (ICGA), optical coherence tomography (OCT), visual acuity (VA) and microperimetry.
   Results: Over 9 months, seven patients gained three to 24 letters and one had unchanged VA. Three patients lost eight to 24 letters due to recurrence and received another verteporfin treatment at month 6. Median retinal sensitivity of the central 4 degrees of the macula increased from 0.9 (SD 2.3) dB (baseline) to 5.2 (1.8) dB (only baseline verteporfin) and 4.1 (4.5) dB (second verteporfin treatment) at study end. OCT showed sub- and intraretinal leakage increased with verteporfin, but resolved after 2 weeks. After combination treatment, CNV was completely occluded on FA within 1 week. ICGA showed non-perfusion of small/medium choroidal vessels. Recovery of choroidal perfusion began after 1 month, but remained impaired throughout follow-up.
   Conclusion: Verteporfin/ranibizumab was associated with CNV occlusion, reduced oedema, improved visual function and retinal sensitivity. The clinical significance of these findings requires further investigation.
C1 [Kiss, C. G.; Simader, C.; Michels, S.; Schmidt-Erfurth, U.] Med Univ Vienna, Dept Ophthalmol, Vienna, Austria.
C3 Medical University of Vienna
RP Schmidt-Erfurth, U (通讯作者)，Univ Vienna, Dept Ophthalmol, Univ Klin Augenheilkunde & Optometrie, AKH Vienna, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
EM ursula.schmidt-erfurth@meduniwien.ac.at
FU Novartis Pharma AG
FX US-E is an inventor on the patent on the use of verteporfin in ocular
   vascular disease under the guidelines of the Wellman Laboratories patent
   policy/Harvard Medical School. She has received financial support from
   Novartis Pharma AG for travel expenses and contributions to conferences
   and advisory boards and institutional support for commercially sponsored
   studies.
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NR 22
TC 18
Z9 20
U1 0
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD DEC
PY 2008
VL 92
IS 12
BP 1620
EP 1627
DI 10.1136/bjo.2007.135335
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 376ZW
UT WOS:000261222500013
PM 19029163
DA 2022-11-30
ER

PT J
AU Rezai, KA
   Gasyna, E
   Seagle, BLL
   Norris, JR
   Rezaei, KA
AF Rezai, Kourous A.
   Gasyna, Elzbieta
   Seagle, Brandon-Luke L.
   Norris, James R., Jr.
   Rezaei, Kasra A.
TI AcrySof natural filter decreases blue light-induced apoptosis in human
   retinal pigment epithelium
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE blue light; RPE; AcrySof
ID AGE-RELATED MACULOPATHY; BEAVER DAM EYE; MACULAR DEGENERATION;
   INTRAOCULAR-LENS; CATARACT-SURGERY; 5-YEAR INCIDENCE; BEEF HEART; CELLS;
   MITOCHONDRIA; LIPOFUSCIN
AB Purpose The effect of AcrySof filter (UV light-filtering chromophore; Alcon) and AcrySof Natural filter (UV- and blue light-filtering chromophores) on blue light-induced apoptosis in human retinal pigment epithelial (RPE) cells was evaluated.
   Design Laboratory investigation
   Clinical relevance Acrysof Natural filter reduces the blue-light toxicity in RPE cells and may have a positive impact on age-related macular degeneration (AMD).
   Methods RPE cells were exposed to blue light (430-450 nm) in the presence of either the AcrySof (UV only) filter or Acrysof Natural (UV and blue light) filter for 10 days. The rate of apoptosis was analyzed.
   Results Blue light induced significant apoptosis in RPE cells. AcrySof Natural filter significantly reduced the blue light-induced apoptosis when compared to AcrySof filter. The amount of blue-light energy reaching the cells with the AcrySof filter was 4.25 mW/cm(2) and with the AcrySof Natural filter was 2.5 mW/cm(2).
   Conclusions AcrySof Natural filter significantly reduced blue light-induced apoptosis. This was most likely due to its filtering effect on blue wavelength light, which reduces the energy that reaches the cells. In patients with cataract who are at a high risk for AMD, the implantation of a blue light-filtering intraocular lens may be considered.
C1 [Rezaei, Kasra A.] Illinois Retina Associates SC, Harvey, IL 60426 USA.
   [Rezai, Kourous A.] Rush Univ, Med Ctr, Dept Ophthalmol, Chicago, IL 60612 USA.
   [Rezai, Kourous A.; Gasyna, Elzbieta] Univ Chicago, Dept Ophthalmol & Visual Sci, Chicago, IL 60637 USA.
   [Seagle, Brandon-Luke L.; Norris, James R., Jr.] Univ Chicago, Dept Chem, Chicago, IL 60637 USA.
   [Seagle, Brandon-Luke L.; Norris, James R., Jr.] Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA.
C3 Rush University; University of Chicago; University of Chicago;
   University of Chicago
RP Rezaei, KA (通讯作者)，Illinois Retina Associates SC, 71 W 156th St,Suite 400, Harvey, IL 60426 USA.
EM karezaei@yahoo.com
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NR 37
TC 24
Z9 28
U1 0
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013 USA
SN 0721-832X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD MAY
PY 2008
VL 246
IS 5
BP 671
EP 676
DI 10.1007/s00417-006-0484-2
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 285JO
UT WOS:000254773300007
PM 18299878
DA 2022-11-30
ER

PT J
AU Marneros, AG
   She, H
   Zambarakji, H
   Hashizume, H
   Connolly, EJ
   Kim, I
   Gragoudas, ES
   Miller, JW
   Olsen, BR
AF Marneros, Alexander G.
   She, Haicheng
   Zambarakji, Hadi
   Hashizume, Hiroya
   Connolly, Edward J.
   Kim, Ivana
   Gragoudas, Evangelos S.
   Miller, Joan W.
   Olsen, Bjorn R.
TI Endogenous endostatin inhibits choroidal neovascularization
SO FASEB JOURNAL
LA English
DT Article
DE angiogenesis; collagen XVIII; Bruch's membrane; age-related macular
   degeneration
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL-PIGMENT EPITHELIUM; COLLAGEN-XVIII;
   MACULAR DEGENERATION; TUMOR-GROWTH; FACTOR VEGF; BASEMENT-MEMBRANE;
   FACTOR EXPRESSION; KNOBLOCH-SYNDROME; AGE
AB Endostatin, a fragment of the basement membrane component collagen XVIII, exhibits antiangiogenic properties in vitro and in vivo when high doses are administered. It is not known whether endogenous endostatin at physiological levels has a protective role as an inhibitor of pathological angiogenesis, such as choroidal neovascularization ( CNV) in age- related macular degeneration. Using a laser injury model, we induced CNV in mice lacking collagen XVIII/ endostatin and in control mice. CNV lesions in mutant mice were similar to 3-fold larger than in control mice and showed increased vascular leakage. These differences were independent of age- related changes at the choroid-retina interface. Ultrastructural analysis of the choroidal vasculature in mutant mice excluded morphological vascular abnormalities as a cause for the larger CNV lesions. When recombinant endostatin was administered to collagen XVIII/ endostatin- deficient mice, CNV lesions were similar to those seen in control mice. In control mice treated with recombinant endostatin, CNV lesions were almost undetectable. These findings demonstrate that endogenous endostatin is an inhibitor of induced angiogenesis and that administration of endostatin potently inhibits CNV growth and vascular leakage. Endostatin may have a regulatory role in the pathogenesis of CNV and could be used therapeutically to inhibit growth and leakage of CNV lesions.
C1 Harvard Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA.
   Harvard Med Sch, Dept Cell Biol, Boston, MA USA.
   Harvard Med Sch, Massachusetts Eye & Ear Infirm, Angiogenesis Lab & Retina Serv, Boston, MA USA.
   Niigata Univ, Postgrad Sch Med & Dental Sci, Div Microscop Anatomy & Bioimaging, Niigata, Japan.
C3 Harvard University; Harvard School of Dental Medicine; Harvard
   University; Harvard Medical School; Harvard University; Harvard Medical
   School; Massachusetts Eye & Ear Infirmary; Niigata University
RP Marneros, AG (通讯作者)，Harvard Sch Dent Med, Dept Dev Biol, 188 Longwood Ave, Boston, MA 02115 USA.
EM alexander_marneros@yahoo.com
RI Zambarakji, Hadi/AAM-6095-2020
OI Marneros, Alexander/0000-0003-3866-020X; Kim, Ivana/0000-0003-0310-6129;
   Miller, Joan/0000-0003-2046-3996
FU NEI NIH HHS [P30EY14104] Funding Source: Medline; NIAMS NIH HHS
   [AR36820] Funding Source: Medline; NATIONAL EYE INSTITUTE [P30EY014104]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ARTHRITIS AND
   MUSCULOSKELETAL AND SKIN DISEASES [R01AR036820, R37AR036820] Funding
   Source: NIH RePORTER
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NR 40
TC 54
Z9 60
U1 1
U2 4
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 DEC
PY 2007
VL 21
IS 14
BP 3809
EP 3818
DI 10.1096/fj.07-8422com
PG 10
WC Biochemistry & Molecular Biology; Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
   Topics; Cell Biology
GA 236DP
UT WOS:000251283500005
PM 17526870
DA 2022-11-30
ER

PT J
AU Liu, WT
   Sivaprakasam, M
   Singh, PR
   Bashirullah, RS
   Wang, GX
AF Liu, WT
   Sivaprakasam, M
   Singh, PR
   Bashirullah, RS
   Wang, GX
TI Electronic visual prosthesis
SO ARTIFICIAL ORGANS
LA English
DT Article
DE retinal prosthesis; telemetry; neurostimulator; inductive link; low
   power design
ID POWER
AB Retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are incurable diseases that result in profound vision loss due to degeneration of the light sensing photoreceptors. However, the discovery that direct electrical stimulation of the retinal neurons creates visual sensation has inspired prosthetic devices aimed to restore useful vision in RP/AMD patients. The approach to one such electronic visual prosthesis is described in this article. The prosthesis consists of an external unit and an internal unit. The communication link has three components-power and data transfer from the external to the internal unit, and data transfer from the internal to the external unit. A novel method of integrating power transfer and back telemetry is described here. The goal is to design a stimulator chip with a small area with low power consumption. This chip, capable of stimulating 60 dedicated electrodes, is fabricated using AMI 1.2 mum process technology and the results are presented. Improvements in the design to increase the number of outputs to 1,000 have been discussed. The new circuit is aimed at increasing the circuit density, reducing power per stimulus, and meeting the requirements more closely than the previous designs. The results of the designed chip are presented.
C1 Univ Calif Santa Cruz, Dept Elect Engn, Santa Cruz, CA 95064 USA.
   N Carolina State Univ, ECE Dept, Raleigh, NC 27695 USA.
C3 University of California System; University of California Santa Cruz;
   University of North Carolina; North Carolina State University
RP Liu, WT (通讯作者)，Univ Calif Santa Cruz, Dept Elect Engn, 1156 High St, Santa Cruz, CA 95064 USA.
EM wentai@soe.ucsc.edu
OI Sivaprakasam, Mohanasankar/0000-0002-6714-9147
CR [Anonymous], VIS HUM PROJ
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NR 22
TC 32
Z9 35
U1 0
U2 6
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0160-564X
EI 1525-1594
J9 ARTIF ORGANS
JI Artif. Organs
PD NOV
PY 2003
VL 27
IS 11
BP 986
EP 995
DI 10.1046/j.1525-1594.2003.07306.x
PG 10
WC Engineering, Biomedical; Transplantation
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Transplantation
GA 742AE
UT WOS:000186491900004
PM 14616517
DA 2022-11-30
ER

PT J
AU Hernandez-Pons, A
   Ortiz-Seller, A
   Lopez-Cruz, I
   Camarena, JJ
   Comin-Perez, A
   Ferrandez-Perez, MA
   Martinez-Costa, L
AF Hernandez-Pons, Antonio
   Ortiz-Seller, Amparo
   Lopez-Cruz, Ian
   Camarena, Juan J.
   Comin-Perez, Alberto
   Ferrandez-Perez, Maria A.
   Martinez-Costa, Lucia
TI Fungal Necrotizing Scleritis After Intravitreal Injection Therapy
SO CORNEA
LA English
DT Article
DE Aspergillus terreus; infectious scleritis; intravitreal injection
   therapy; voriconazole
AB Purpose: To report a case of infectious necrotizing scleritis secondary to Aspergillus terreus after intravitreal injection therapy. Methods: This is a case report with literature review. Results: A 98-year-old woman receiving intravitreal aflibercept injections for neovascular age-related macular degeneration in the left eye presented with severe pain, redness, and purulent discharge at the injection site. She was initially treated with topical fortified antibiotics, and clinical improvement was achieved, although microbial cultures showed negative results. Two months later, she presented with severe ocular pain and was diagnosed with anterior necrotizing scleritis. Scleral scrapings were collected for cultures, and intensive topical antibiotic therapy was reintroduced. Evaluation for autoimmune etiology and microbiological testing showed negative results. Because of the progression of the scleral necrotic area, empirical therapy with topical voriconazole was initiated, and surgical debridement was performed. Finally, the culture was positive for A. terreus. The modified therapy consisted of topical voriconazole and oral voriconazole for 3 months with an excellent clinical outcome. Conclusions: To our knowledge, this is the first case of fungal necrotizing scleritis secondary to intravitreal injection. Diagnosis was delayed due to its chronic clinical course and the slow fungal growth in culture media, but the combined medical and surgical approach resulted in a satisfactory outcome.
C1 [Hernandez-Pons, Antonio; Ortiz-Seller, Amparo; Comin-Perez, Alberto; Ferrandez-Perez, Maria A.; Martinez-Costa, Lucia] Hosp Univ Doctor Peset, Dept Ophthalmol, C Juan de Garay 21, ES-46017 Valencia, Spain.
   [Lopez-Cruz, Ian] Hosp Univ Doctor Peset, Dept Internal Med, Valencia, Spain.
   [Camarena, Juan J.] Univ Valencia UV, Hosp Univ Doctor Peset, Dept Microbiol, Valencia, Spain.
C3 University of Valencia
RP Hernandez-Pons, A (通讯作者)，Hosp Univ Doctor Peset, Dept Ophthalmol, C Juan de Garay 21, ES-46017 Valencia, Spain.
EM herpons@gmail.com
RI Hernández-Pons, Antonio/AAL-1748-2021
OI Ortiz-Seller, Amparo/0000-0003-0200-1667; Lopez-Cruz,
   Ian/0000-0001-7252-8961
CR Baddley JW, 2003, J CLIN MICROBIOL, V41, P5525, DOI 10.1128/JCM.41.12.5525-5529.2003
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NR 11
TC 2
Z9 2
U1 2
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0277-3740
EI 1536-4798
J9 CORNEA
JI Cornea
PD DEC
PY 2021
VL 40
IS 12
BP 1617
EP 1619
DI 10.1097/ICO.0000000000002670
PG 3
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA WS9FK
UT WOS:000715481500020
PM 34749383
DA 2022-11-30
ER

PT J
AU Saddala, MS
   Lennikov, A
   Mukwaya, A
   Huang, H
AF Saddala, Madhu Sudhana
   Lennikov, Anton
   Mukwaya, Anthony
   Huang, Hu
TI Transcriptome-Wide Analysis of CXCR5 Deficient Retinal Pigment
   Epithelial (RPE) Cells Reveals Molecular Signatures of RPE Homeostasis
SO BIOMEDICINES
LA English
DT Article
DE age-related macular degeneration; CXCR5; EMT; FoxO; Mitochondria;
   RNA-Seq; gene ontology; KEGG; retinal pigment epithelium
ID NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; MESENCHYMAL TRANSITION; MACULAR
   DEGENERATION; OXIDATIVE STRESS; GROWTH-FACTOR; AUTOPHAGY; ACTIVATION;
   APOPTOSIS; PROTEIN
AB Age-related macular degeneration (AMD) is the most common cause of irreversible blindness in the elderly population. In our previous studies, we found that deficiency of CXCR5 causes AMD-like pathological phenotypes in mice, characterized by abnormalities and dysfunction of the retinal pigment epithelium (RPE) cells. The abnormalities included abnormal cellular shape and impaired barrier function. In the present study, primary RPE cells were derived separately from CXCR5 knockout (KO) mice and from C57BL6 wild type (WT). The isolated primary cells were cultured for several days, and then total RNA was isolated and used for library preparation, sequencing, and the resultant raw data analyzed. Relative to the WT, a total of 1392 differentially expressed genes (DEG) were identified. Gene ontology analysis showed various biological processes, cellular components, and molecular functions were enriched. Pathway enrichment analysis revealed several pathways, including the PI3K-Akt signaling, mTOR signaling, FoxO, focal adhesion, endocytosis, ubiquitin-mediated proteolysis, TNF alpha-NF-kappa B Signaling, adipogenesis genes, p53 signaling, Ras, autophagy, epithelial-mesenchymal transition (EMT), and mitochondrial pathway. This study explores molecular signatures associated with deficiency of CXCR5 in RPE cells. Many of these signatures are important for homeostasis of this tissue. The identified pathways and genes require further evaluation to better understand the pathophysiology of AMD.
C1 [Saddala, Madhu Sudhana; Lennikov, Anton; Huang, Hu] Univ Missouri, Dept Ophthalmol, Columbia, MO 65212 USA.
   [Mukwaya, Anthony] Linkoping Univ, Fac Hlth Sci, Inst Clin & Expt Med, Dept Ophthalmol, S-58183 Linkoping, Sweden.
C3 University of Missouri System; University of Missouri Columbia;
   Linkoping University
RP Huang, H (通讯作者)，Univ Missouri, Dept Ophthalmol, Columbia, MO 65212 USA.
EM saddalam@missouri.edu; lennikova@missouri.edu; anthonny.mukwaya@liu.se;
   huangh1@missouri.edu
RI Mukwaya, Anthony/K-2335-2019; Saddala, Madhu Sudhana/C-6147-2018
OI Mukwaya, Anthony/0000-0002-9645-8942; Saddala, Madhu
   Sudhana/0000-0002-6373-7080
FU University of Missouri; National Eye Institute (NEI), Bethesda, MD, USA
   [EY027824]
FX This work was supported by the University of Missouri start-up funds (Hu
   Huang) and National Eye Institute (NEI), Bethesda, MD, USA grant
   EY027824.
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NR 53
TC 6
Z9 6
U1 0
U2 4
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2227-9059
J9 BIOMEDICINES
JI Biomedicines
PD JUN
PY 2020
VL 8
IS 6
AR 147
DI 10.3390/biomedicines8060147
PG 19
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental;
   Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Research & Experimental Medicine;
   Pharmacology & Pharmacy
GA MO0NC
UT WOS:000551233000027
PM 32492870
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Di Marco, S
   Riccitelli, S
   Di Paolo, M
   Campos, E
   Buzzi, M
   Bisti, S
   Versura, P
AF Di Marco, Stefano
   Riccitelli, Serena
   Di Paolo, Mattia
   Campos, Emilio
   Buzzi, Marina
   Bisti, Silvia
   Versura, Piera
TI Cord Blood Serum (CBS)-Based Eye Drops Modulate Light-Induced
   Neurodegeneration in Albino Rat Retinas
SO BIOMOLECULES
LA English
DT Article
DE photoreceptor neurodegeneration; retina; trophic factor; cord blood
   serum
ID PHOTORECEPTOR DEATH; DAMAGING LIGHT; UP-REGULATION; MECHANISMS;
   EXPOSURE; CORNEAL
AB Age-related macular degeneration (AMD) is one of the leading causes of visual loss in western countries, it has no cure, and its incidence will grow in the future, for the overall population aging. Albino rats with retinal degeneration induced by exposure to high-intensity light (light-damage, LD) have been extensively used as a model of AMD to test neuroprotective agents. Among them, trophic factors (NGF and BDNF) have been shown to play a significant role in photoreceptors' survival. Interestingly, cord blood serum (CBS) is an extract full of chemokines and trophic factors; we, therefore, hypothesized that CBS could be an excellent candidate for neuroprotection. Here, we investigate whether CBS-based eye drops might mitigate the effects of light-induced retinal degeneration in albino rats. CBS treatment significantly preserved flash-electroretinogram (f-ERG) response after LD and reduced the "hot-spot" extension. Besides, CBS-treated animals better preserved the morphology of the outer nuclear layer, together with a reduction in microglia migration and activation. Interestingly, the treatment did not modulate reactive gliosis and activation of the self-protective mechanism (FGF2). In conclusion, our results suggest that CBS-based eye drops might be successfully used to mitigate retinal neurodegenerative processes such as AMD.
C1 [Di Marco, Stefano; Riccitelli, Serena; Di Paolo, Mattia; Bisti, Silvia] Univ Aquila, Dept Appl Clin Sci & Biotechnol, Via Vetoio,Coppito 2, I-67100 Laquila, Italy.
   [Di Marco, Stefano; Bisti, Silvia] Ist Nazl Biostrutture & Biosistemi INBB, Via Medaglie dOro 305, I-00136 Rome, Italy.
   [Di Marco, Stefano] Ist Italiano Tecnol, Ctr Synapt Neurosci & Technol, I-16132 Genoa, Italy.
   [Di Marco, Stefano] IRCCS, Osped & Policlin San Martino, I-16132 Genoa, Italy.
   [Campos, Emilio; Versura, Piera] Univ Bologna, Ophthalmol Unit, I-40138 Bologna, Italy.
   [Campos, Emilio; Versura, Piera] S Orsola Malpighi Teaching Hosp, I-40138 Bologna, Italy.
   [Buzzi, Marina] S Orsola Malpighi Teaching Hosp, Cord Blood Bank, Transfus Serv, I-40138 Bologna, Emilia Romagna, Italy.
   [Bisti, Silvia] Ist Italiano Tecnol, NetS3 Lab, Via Morego 30, I-16163 Genoa, Italy.
C3 University of L'Aquila; Istituto Italiano di Tecnologia - IIT;
   University of Bologna; IRCCS Azienda Ospedaliero-Universitaria di
   Bologna; IRCCS Azienda Ospedaliero-Universitaria di Bologna; Istituto
   Italiano di Tecnologia - IIT
RP Di Marco, S; Bisti, S (通讯作者)，Univ Aquila, Dept Appl Clin Sci & Biotechnol, Via Vetoio,Coppito 2, I-67100 Laquila, Italy.; Di Marco, S; Bisti, S (通讯作者)，Ist Nazl Biostrutture & Biosistemi INBB, Via Medaglie dOro 305, I-00136 Rome, Italy.; Di Marco, S (通讯作者)，Ist Italiano Tecnol, Ctr Synapt Neurosci & Technol, I-16132 Genoa, Italy.; Di Marco, S (通讯作者)，IRCCS, Osped & Policlin San Martino, I-16132 Genoa, Italy.; Bisti, S (通讯作者)，Ist Italiano Tecnol, NetS3 Lab, Via Morego 30, I-16163 Genoa, Italy.
EM Stefano.dimarco@iit.it; serena.riccitelli@graduate.univaq.it;
   mattia.dipaolo@univaq.it; emiliocarlocampos@gmail.com;
   Marina.Buzzi@aosp.bo.it; Silvia.Bisti@iit.it; piera.versura@aosp.bo.it
RI Versura, P/J-1361-2019; Di Marco, Stefano/AAO-8073-2020; Di+Paolo,
   Mattia/AAX-3592-2021
OI Versura, P/0000-0002-2951-5337; Di Marco, Stefano/0000-0003-4847-6270;
   Riccitelli, Serena/0000-0003-4369-4586
FU Fondazione Cassa di Risparmio in Bologna [2019-0547]; Beneficientia
   Stiftung-Vaduz [BEN 2015/94]; Fondazione Cassa di Risparmio in Bologna
FX This research was funded by Fondazione Cassa di Risparmio in Bologna
   grant number [2019-0547] and by [Beneficientia Stiftung-Vaduz] grant
   number [BEN 2015/94]. The APC was funded by Fondazione Cassa di
   Risparmio in Bologna.
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NR 22
TC 3
Z9 3
U1 0
U2 1
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2218-273X
J9 BIOMOLECULES
JI Biomolecules
PD MAY
PY 2020
VL 10
IS 5
AR 678
DI 10.3390/biom10050678
PG 11
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA ME9ZV
UT WOS:000545013700015
PM 32354031
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Hu, K
   Shen, BW
   Zhang, Y
   Cao, CH
   Xiao, F
   Gao, XP
AF Hu, Kai
   Shen, Binwei
   Zhang, Yuan
   Cao, Chunhong
   Xiao, Fen
   Gao, Xieping
TI Automatic segmentation of retinal layer boundaries in OCT images using
   multiscale convolutional neural network and graph search
SO NEUROCOMPUTING
LA English
DT Article
DE Optical coherence tomography; Retinal layer boundary; Segmentation;
   Multiscale convolutional neural network; Graph search
ID THICKNESS
AB Accurate quantitative analysis of the retinal layer in optical coherence tomography (OCT) images plays a crucial role in detecting and diagnosing ocular diseases. In this paper, we present a novel automatic method by combining multiscale convolutional neural network (MCNN) and graph search to accurately segment multiple retinal layer boundaries in OCT images. Firstly, we propose a MCNN architecture to extract multiscale features of retinal layer boundaries and thus to produce probability maps of the retinal layer boundaries. Especially, we construct a MCNN architecture by fusing feature maps extracted from different sizes of input image patches to learn multiscale information about the retinal layer boundaries. Meanwhile, we distinguish the background pixels based on the location information to reduce the probability that the network misclassifies the background as a target. Furthermore, we propose an improved graph search algorithm to detect the final layer boundaries from the probability maps. Finally, we evaluate our proposed method with eight state-of-the-art approaches on a publicly OCT dataset with age-related macular degeneration (AMD). The experimental results demonstrate that the proposed method outperforms other state-of-the-art approaches in terms of quantitative results and visual effects. (C) 2019 Elsevier B.V. All rights reserved.
C1 [Hu, Kai; Shen, Binwei; Zhang, Yuan; Cao, Chunhong; Xiao, Fen; Gao, Xieping] Xiangtan Univ, Key Lab Intelligent Comp & Informat Proc, Minist Educ, Xiangtan 411105, Peoples R China.
   [Hu, Kai] Xiangtan Univ, Postdoctoral Res Stn Mech, Xiangtan 411105, Peoples R China.
   [Gao, Xieping] Xiangnan Univ, Coll Software & Commun Engn, Chenzhou 423043, Peoples R China.
C3 Xiangtan University; Xiangtan University; Xiangnan University
RP Gao, XP (通讯作者)，Xiangtan Univ, Key Lab Intelligent Comp & Informat Proc, Minist Educ, Xiangtan 411105, Peoples R China.
EM xpgao@xtu.edu.cn
OI Xiao, Fen/0000-0001-7511-9418
FU National Natural Science Foundation of China [61802328, 61771415];
   Natural Science Foundation of Hunan Province in China [2019JJ50606];
   Cernet Innovation Project [NGII20170702]
FX The authors would like to thank Dr. Stephanie J. Chiu from Duke
   University for some helpful discussions about the experiment. The
   authors would also like to thank the anonymous reviewers for their
   insightful comments, which have helped to improve the content of this
   paper. This work was supported in part by the National Natural Science
   Foundation of China under Grants 61802328 and 61771415, in part by the
   Natural Science Foundation of Hunan Province in China under Grant
   2019JJ50606, and in part by the Cernet Innovation Project under Grant
   NGII20170702.
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NR 40
TC 21
Z9 21
U1 2
U2 32
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0925-2312
EI 1872-8286
J9 NEUROCOMPUTING
JI Neurocomputing
PD NOV 6
PY 2019
VL 365
BP 302
EP 313
DI 10.1016/j.neucom.2019.07.079
PG 12
WC Computer Science, Artificial Intelligence
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science
GA IV1XR
UT WOS:000484072600028
DA 2022-11-30
ER

PT J
AU Xue, K
   Zhao, XX
   Zhang, ZX
   Qiu, BY
   Tan, QSW
   Ong, KH
   Liu, ZP
   Parikh, BH
   Barathi, VA
   Yu, WM
   Wang, XM
   Lingam, G
   Hunziker, W
   Su, XY
   Loh, XJ
AF Xue, Kun
   Zhao, Xinxin
   Zhang, Zhongxing
   Qiu, Beiying
   Tan, Queenie Shu Woon
   Ong, Kok Haur
   Liu, Zengping
   Parikh, Bhav Harshad
   Barathi, Veluchamy Amutha
   Yu, Weimiao
   Wang, Xiaomeng
   Lingam, Gopal
   Hunziker, Walter
   Su, Xinyi
   Loh, Xian Jun
TI Sustained delivery of anti-VEGFs from thermogel depots inhibits
   angiogenesis without the need for multiple injections
SO BIOMATERIALS SCIENCE
LA English
DT Article
ID INJECTABLE HYDROGELS; CONTROLLED-RELEASE; BLOCK-COPOLYMERS; NETWORK
   DESIGN; DRUG; PROTEINS; BEVACIZUMAB; CHALLENGES; STRATEGIES; POLYMERS
AB Anti-vascular endothelial growth factor (anti-VEGF) proteins are the gold-standard treatment for posterior eye segment proliferative vascular diseases such as Age-Related Macular Degeneration (AMD) and Diabetic Retinopathy (DR). However, the standard of care requires inconvenient monthly intravitreal injections. This underlies an unmet clinical need to develop alternative solutions for sustained delivery of biologics. In this paper, we demonstrated that anti-VEGFs can be encapsulated by a simple mild process into our polyurethane thermogel depots. By changing the hydrophilic-hydrophobic balance in the copolymer, anti-VEGF release rates can be modulated. The antibody in the thermogel partitions into protein domains which vary in size corresponding to the hydrophilicity balance of the polymer. Anti-VEGFs can be released in a relatively linear manner from the thermogel for up to 40 days in vitro. The encapsulated anti-VEGFs demonstrate anti-angiogenic bioactivity by inhibiting vessel outgrowth in rat ex vivo choroidal explants, and reducing vascular leakage in a VEGF-driven neovascularization rabbit model. In conclusion, we show that these thermogels can be tuned in terms of hydrophilicity and used for sustained delivery of bioactive anti-VEGFs. Physically cross-linked polyurethane thermoresponsive hydrogels could be a promising platform for sustained delivery of biologically active therapeutic proteins.
C1 [Xue, Kun; Zhang, Zhongxing; Loh, Xian Jun] ASTAR, IMRE, 2 Fusionopolis Way,08-03 Innovis, Singapore 138634, Singapore.
   [Zhao, Xinxin; Qiu, Beiying; Tan, Queenie Shu Woon; Ong, Kok Haur; Parikh, Bhav Harshad; Yu, Weimiao; Wang, Xiaomeng; Hunziker, Walter; Su, Xinyi] ASTAR, IMCB, 61 Biopolis Dr Proteos, Singapore 138673, Singapore.
   [Liu, Zengping; Parikh, Bhav Harshad; Barathi, Veluchamy Amutha; Lingam, Gopal; Su, Xinyi] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, 1E Kent Ridge Rd,NUHS Tower Block,Level 7, Singapore 119228, Singapore.
   [Liu, Zengping; Barathi, Veluchamy Amutha; Wang, Xiaomeng; Su, Xinyi; Loh, Xian Jun] Singapore Eye Res Inst, 11 Third Hosp Ave, Singapore 168751, Singapore.
   [Barathi, Veluchamy Amutha] Duke NUS Grad Sch Med, Acad Clin Program Ophthalmol, Singapore, Singapore.
   [Wang, Xiaomeng] Nanyang Technol Univ Singapore, Lee Kong Chian Sch Med, 59 Nanyang Dr, Singapore 636921, Singapore.
   [Loh, Xian Jun] Natl Univ Singapore, Dept Mat Sci & Engn, 9 Engn Dr 1, Singapore 117575, Singapore.
C3 Agency for Science Technology & Research (A*STAR); A*STAR - Institute of
   Materials Research & Engineering (IMRE); Agency for Science Technology &
   Research (A*STAR); A*STAR - Institute of Molecular & Cell Biology
   (IMCB); National University of Singapore; National University of
   Singapore; Singapore National Eye Center; National University of
   Singapore; Nanyang Technological University & National Institute of
   Education (NIE) Singapore; Nanyang Technological University; National
   University of Singapore
RP Loh, XJ (通讯作者)，ASTAR, IMRE, 2 Fusionopolis Way,08-03 Innovis, Singapore 138634, Singapore.; Su, XY (通讯作者)，ASTAR, IMCB, 61 Biopolis Dr Proteos, Singapore 138673, Singapore.; Su, XY (通讯作者)，Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, 1E Kent Ridge Rd,NUHS Tower Block,Level 7, Singapore 119228, Singapore.; Su, XY; Loh, XJ (通讯作者)，Singapore Eye Res Inst, 11 Third Hosp Ave, Singapore 168751, Singapore.; Loh, XJ (通讯作者)，Natl Univ Singapore, Dept Mat Sci & Engn, 9 Engn Dr 1, Singapore 117575, Singapore.
EM xysu@imcb.a-star.edu.sg; lohxj@imre.a-star.edu.sg
RI Yu, Weimiao/AAN-4790-2020; Hunziker, Walter/B-3140-2010; Zhang,
   Zhongxing/N-3486-2014; Loh, Xian Jun/H-6260-2013; Liu,
   Zengping/GQO-9030-2022; Hunziker, Walter/GSM-8190-2022
OI Hunziker, Walter/0000-0002-5265-4933; Loh, Xian Jun/0000-0001-8118-6502;
   Liu, Zengping/0000-0002-2578-293X; Xue, Kun/0000-0002-5433-0297; Wang,
   Xiaomeng/0000-0002-1036-2764; Barathi, Veluchamy
   Amutha/0000-0002-6477-9784
FU  [H17/01/a0/013]
FX This study was supported by an IAF-PP (HMBS Domain) grant H17/01/a0/013
   (OrBID): OculaR BIomaterials and Device. We would like to acknowledge
   Jason Y. C. Lim and Dan Kai for helpful discussions.
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NR 72
TC 35
Z9 35
U1 1
U2 40
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
   ENGLAND
SN 2047-4830
EI 2047-4849
J9 BIOMATER SCI-UK
JI Biomater. Sci.
PD NOV 1
PY 2019
VL 7
IS 11
BP 4603
EP 4614
DI 10.1039/c9bm01049a
PG 12
WC Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Materials Science
GA JQ2ZM
UT WOS:000498818900012
PM 31436780
DA 2022-11-30
ER

PT J
AU Saha, S
   Nassisi, M
   Wang, M
   Lindenberg, S
   Kanagasingam, Y
   Sadda, S
   Hu, ZJ
AF Saha, Sajib
   Nassisi, Marco
   Wang, Mo
   Lindenberg, Sophiana
   Kanagasingam, Yogi
   Sadda, Srinivas
   Hu, Zhihong Jewel
TI Automated detection and classification of early AMD biomarkers using
   deep learning
SO SCIENTIFIC REPORTS
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; AGE-RELATED MACULOPATHY; MACULAR
   DEGENERATION; GEOGRAPHIC-ATROPHY; SD-OCT; RETICULAR PSEUDODRUSEN;
   SEVERITY SCALE; RETINAL LAYER; FELLOW-EYES; SEGMENTATION
AB Age-related macular degeneration (AMD) affects millions of people and is a leading cause of blindness throughout the world. Ideally, affected individuals would be identified at an early stage before late sequelae such as outer retinal atrophy or exudative neovascular membranes develop, which could produce irreversible visual loss. Early identification could allow patients to be staged and appropriate monitoring intervals to be established. Accurate staging of earlier AMD stages could also facilitate the development of new preventative therapeutics. However, accurate and precise staging of AMD, particularly using newer optical coherence tomography (OCT)-based biomarkers may be time-intensive and requires expert training which may not feasible in many circumstances, particularly in screening settings. In this work we develop deep learning method for automated detection and classification of early AMD OCT biomarker. Deep convolution neural networks (CNN) were explicitly trained for performing automated detection and classification of hyperreflective foci, hyporeflective foci within the drusen, and subretinal drusenoid deposits from OCT B-scans. Numerous experiments were conducted to evaluate the performance of several state-of-the-art CNNs and different transfer learning protocols on an image dataset containing approximately 20000 OCT B-scans from 153 patients. An overall accuracy of 87% for identifying the presence of early AMD biomarkers was achieved.
C1 [Saha, Sajib; Nassisi, Marco; Wang, Mo; Lindenberg, Sophiana; Sadda, Srinivas; Hu, Zhihong Jewel] Doheny Eye Inst, Los Angeles, CA 90033 USA.
   [Sadda, Srinivas] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90033 USA.
   [Saha, Sajib; Kanagasingam, Yogi] CSIRO, Australian E Hlth Res Ctr, Perth, WA, Australia.
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; Commonwealth Scientific
   & Industrial Research Organisation (CSIRO)
RP Hu, ZJ (通讯作者)，Doheny Eye Inst, Los Angeles, CA 90033 USA.
EM jhu@doheny.org
RI Nassisi, Marco/P-9939-2019
OI Nassisi, Marco/0000-0002-9354-9005; Hu, Zhihong/0000-0001-8307-0298
FU NIH-NEI [R21-EY030619]; Australia Endeavour Scholarships and
   Fellowships; BrightFocus Foundation Macular Degeneration program; Macula
   Vision Research Foundation (MVRF); NATIONAL EYE INSTITUTE [R21EY030619]
   Funding Source: NIH RePORTER
FX This work was supported, in part, by NIH-NEI grant R21-EY030619, an
   award from Australia Endeavour Scholarships and Fellowships, a grant
   from the BrightFocus Foundation Macular Degeneration program, and a
   grant from Macula Vision Research Foundation (MVRF).
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NR 51
TC 27
Z9 28
U1 0
U2 7
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUL 29
PY 2019
VL 9
AR 10990
DI 10.1038/s41598-019-47390-3
PG 9
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA IM0TG
UT WOS:000477701800093
PM 31358808
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Yanagisawa, M
   Kato, S
   Ochiai, M
AF Yanagisawa, Mieko
   Kato, Satoshi
   Ochiai, Makiko
TI Comparison of Esterman disability scores obtained using Goldmann
   perimetry and the Humphrey field analyzer in Japanese low-vision
   patients
SO PLOS ONE
LA English
DT Article
ID QUALITY-OF-LIFE; VISUAL-FIELD; GLAUCOMA; SEVERITY
AB Purpose
   To compare the Esterman Disability Score (EDS) obtained with Goldmann perimetry (GP) testing and the Humphrey field analyzer (HFA) in low vision Japanese subjects. Subjects were also divided into groups by diagnosis to examine how disease influences EDS measurements.
   Methods
   The EDS was obtained using GP (GP-EDS) and the built-in testing program of the HFA (HFA-EDS). Tests were performed within 3 months of each other. Regression analyses were used to examine the relationship between GP-EDS and HFA-EDS.
   Results
   A total of 128 visually impaired subjects were included in this study. Subjects had low vision because of glaucoma (57 subjects), age-related macular degeneration (AMD, 17 subjects), retinitis pigmentosa (RP, 17 subjects), and other causes (37 subjects). The GP-EDS obtained was well-correlated with HFA-EDS (r = 0.87, P < 0.001) and it was possible to estimate HFA-EDS from GP-EDS. The GP-EDS was significantly lower than the HFA-EDS in eyes with glaucoma and RP. There was no significant difference between EDS values in eyes with AMD or other disease.
   Conclusion
   The GP-EDS correlated well with the HFA-EDS. However, the relationship between the EDS measured with the two different testing modalities varies by disease.
C1 [Yanagisawa, Mieko; Kato, Satoshi; Ochiai, Makiko] Univ Tokyo, Grad Sch Med, Dept Ophthalmol, Tokyo, Japan.
C3 University of Tokyo
RP Yanagisawa, M (通讯作者)，Univ Tokyo, Grad Sch Med, Dept Ophthalmol, Tokyo, Japan.
EM yana-tky@umin.ac.jp
FU JSPS KAKENHI [15K10833]
FX This work received support from JSPS KAKENHI Grant 15K10833 to Dr
   Satoshi Kato. 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 19
TC 2
Z9 2
U1 2
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 SEP 13
PY 2018
VL 13
IS 9
AR e0203258
DI 10.1371/journal.pone.0203258
PG 9
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA GT5KH
UT WOS:000444545800029
PM 30212488
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Lee, CS
   Kim, AJ
   Baughman, D
   Egan, C
   Bailey, C
   Johnston, RL
   Natha, S
   Khan, R
   Brand, C
   Akerele, T
   McKibbin, M
   Downey, L
   Al-Husainy, S
   Lee, AY
   Tufail, A
AF Lee, Cecilia S.
   Kim, Alisa J.
   Baughman, Douglas
   Egan, Catherine
   Bailey, Clare
   Johnston, Robert L.
   Natha, Salim
   Khan, Rehna
   Brand, Christopher
   Akerele, Toks
   McKibbin, Martin
   Downey, Louise
   Al-Husainy, Saher
   Lee, Aaron Y.
   Tufail, Adnan
TI VISUAL ACUITY IMPROVEMENT WHEN SWITCHING FROM RANIBIZUMAB TO AFLIBERCEPT
   IS NOT SUSTAINED
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE aflibercept; age-related macular degeneration; choroidal
   neovascularization; ranibizumab; tachyphylaxis; vascular endothelial
   growth factor
ID MACULAR DEGENERATION; INTRAVITREAL AFLIBERCEPT; ANATOMICAL OUTCOMES;
   BEVACIZUMAB; EYES; TACHYPHYLAXIS; PREVALENCE; CONVERSION; RESISTANT;
   RECURRENT
AB Purpose: To assess whether visual benefits exist in switching to aflibercept in patients who have been chronically treated with ranibizumab for neovascular age-related macular degeneration.
   Methods: A multicenter, national, electronic medical record database study was performed. Patients undergoing six continuous monthly ranibizumab injections and then switched to continuous aflibercept were matched to those on continuous ranibizumab therapy. Matching was performed in a 2: 1 ratio and based on visual acuity 6 months before and at the time of the switch, and the number of previous ranibizumab injections.
   Results: Patients who were switched to aflibercept demonstrated transiently significant improvement in visual acuity that peaked at an increase of 0.9 Early Treatment Diabetic Retinopathy Study letters 3 months after the switch, whereas control patients continued on ranibizumab treatment showed a steady decline in visual acuity. Visual acuity differences between the groups were significant (P < 0.05) at 2, 3, and 5 months after the switch. Beginning at 4 months after the switch, the switch group showed a visual acuity decline similar to the control group.
   Conclusion: Transient, nonsustained improvement in visual acuity occurs when switching between anti-vascular endothelial growth factor agents, which may have implications in treating patients on chronic maintenance therapy on one anti-vascular endothelial growth factor medication.
C1 [Lee, Cecilia S.; Lee, Aaron Y.] Univ Washington, Dept Ophthalmol, Box 359607,325 Ninth Ave, Seattle, WA 98104 USA.
   [Kim, Alisa J.; Baughman, Douglas] Univ Washington, Seattle, WA 98104 USA.
   [Egan, Catherine; Tufail, Adnan] Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr, London, England.
   [Egan, Catherine; Tufail, Adnan] UCL Inst Ophthalmol, London, England.
   [Bailey, Clare] Univ Hosp Bristol NHS Fdn Trust, Bristol Eye Hosp, Bristol, Avon, England.
   [Johnston, Robert L.] Gloucestershire Hosp NHS Fdn Trust, Cheltenham, Glos, England.
   [Natha, Salim] Wrightington Wigan & Leigh NHS Fdn Trust, Wigan, England.
   [Khan, Rehna] Calderdale & Huddersfield NHS Fdn Trust, Huddersfield, W Yorkshire, England.
   [Brand, Christopher] Sheffield Teaching Hosp NHS Fdn Trust, Sheffield, S Yorkshire, England.
   [Akerele, Toks] Hinchingbrooke Hlth Care NHS Trust, Huntingdon, England.
   Leeds Teaching Hosp NHS Trust, Leeds, W Yorkshire, England.
   [McKibbin, Martin] Mid Yorkshire Hosp NHS Trust, Kingston Upon Hull, N Humberside, England.
   [Downey, Louise] Hull & East Yorkshire Hosp NHS Trust, Kingston Upon Hull, N Humberside, England.
   [Al-Husainy, Saher] Heart England NHS Fdn Trust, Solihull, W Midlands, England.
C3 University of Washington; University of Washington Seattle; University
   of Washington; University of Washington Seattle; University of London;
   University College London; Moorfields Eye Hospital NHS Foundation Trust;
   University of London; University College London; Bristol Eye Hospital;
   University of Bristol; Gloucestershire Hospitals NHS Foundation Trust;
   University of Sheffield; University of Leeds; Heart of England NHS
   Foundation Trust
RP Lee, AY (通讯作者)，Univ Washington, Dept Ophthalmol, Box 359607,325 Ninth Ave, Seattle, WA 98104 USA.
EM leeay@uw.edu
RI Lee, Aaron/AAT-2839-2020
OI Tufail, Adnan/0000-0001-6131-7640; Lee, Aaron/0000-0002-7452-1648; Egan,
   Catherine/0000-0001-5593-1169
FU National Eye Institute, Bethesda, MD [K23EY02492]; Research to Prevent
   Blindness, Inc, New York, NY; Department of Health, United Kingdom, NIHR
   Biomedical Research Centre for Ophthalmology (Moorfields Eye Hospital,
   University College London), London, United Kingdom; NATIONAL EYE
   INSTITUTE [K23EY024921] Funding Source: NIH RePORTER
FX Supported by National Eye Institute, Bethesda, MD, K23EY02492 (C.S.L.),
   Research to Prevent Blindness, Inc, New York, NY (C.S.L. and A.Y.L.);
   Department of Health, United Kingdom, NIHR Biomedical Research Centre
   for Ophthalmology (Moorfields Eye Hospital, University College London),
   London, United Kingdom (A.T.).
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NR 31
TC 5
Z9 5
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD MAY
PY 2018
VL 38
IS 5
BP 951
EP 956
DI 10.1097/IAE.0000000000001637
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GP2BU
UT WOS:000440625700021
PM 28406859
OA Green Accepted, Green Submitted
DA 2022-11-30
ER

PT J
AU Wang, J
   Feng, YJ
   Han, P
   Wang, FH
   Luo, XT
   Liang, J
   Sun, XJ
   Ye, J
   Lu, YM
   Sun, XD
AF Wang, Jing
   Feng, Yiji
   Han, Peng
   Wang, Fenghua
   Luo, Xueting
   Liang, Jian
   Sun, Xiangjun
   Ye, Jing
   Lu, Yiming
   Sun, Xiaodong
TI Photosensitization of A2E triggers telomere dysfunction and accelerates
   retinal pigment epithelium senescence
SO CELL DEATH & DISEASE
LA English
DT Article
ID MITOCHONDRIAL-DNA DAMAGE; MACULAR DEGENERATION; OXIDATIVE STRESS;
   GEOGRAPHIC ATROPHY; CELLS; EXPRESSION; RPE; FLUOROPHORE; LIPOFUSCIN
AB Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in elderly people. AMD is classified as early, intermediate, advanced non-neovascular, and advanced neovascular forms depending on the clinical features. However, the exact pathogenesis remains unclear. Retinal pigment epithelium (RPE) cells degeneration is a hallmark of AMD. With aging, lipofuscin accumulates in RPE cells. N-retinylidene-N-retinylethanolamine (named A2E), a well-known fluorophore of lipofuscin, may contribute to RPE cells degeneration. In this study, we showed that photosensitization of A2E increased DNA damage, including telomere deprotection and deletion, and triggered cellular senescence. In addition, we found that the antioxidant N-acetyl-cysteine (NAC) partially alleviated this DNA damage. Telomerase overexpression rescued A2E-mediated RPE cell senescence, indicating that telomere dysfunction plays an important role in A2E-based senescence. We further showed that the senescence induced by A2E photosensitization may affect the microenvironment of the retina by expressing several factors of the secretory phenotype (SASP) including IL1B, IL13RA2, and CXCR4 through the NF-kappa B pathway. We propose that expression of these factors create a pro-inflammatory environment that drives retina degeneration. Moreover, our findings suggest that protecting telomeres is a valuable strategy for treating retinal degeneration diseases, such as AMD.
C1 [Wang, Jing; Feng, Yiji; Wang, Fenghua; Sun, Xiaodong] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 1, Shanghai Gen Hosp, Dept Ophthalmol,Sch Med, 100 HaiNing Rd, Shanghai 200080, Peoples R China.
   [Wang, Jing; Han, Peng; Ye, Jing; Lu, Yiming] Shanghai Jiao Tong Univ, Univ Nice, Ruijin Hosp,CNRS,INSERM,Pole Sinofrancais Rech Sc, Shanghai Ruijin Hosp,Int Hematol & Canc LIA,Sch M, Shanghai 200025, Peoples R China.
   [Wang, Fenghua; Luo, Xueting; Liang, Jian; Sun, Xiaodong] Shanghai Engn Ctr Visual Sci & Photomed, Shanghai, Peoples R China.
   [Luo, Xueting; Liang, Jian; Sun, Xiaodong] Shanghai Key Lab Ocular Fundus Dis, Shanghai, Peoples R China.
   [Sun, Xiangjun] Shanghai Jiao Tong Univ, Sch Biol & Agr, Shanghai, Peoples R China.
C3 Shanghai Jiao Tong University; Institut National de la Sante et de la
   Recherche Medicale (Inserm); Shanghai Jiao Tong University; Shanghai
   Jiao Tong University
RP Sun, XD (通讯作者)，Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 1, Shanghai Gen Hosp, Dept Ophthalmol,Sch Med, 100 HaiNing Rd, Shanghai 200080, Peoples R China.; Lu, YM (通讯作者)，Shanghai Jiao Tong Univ, Univ Nice, Ruijin Hosp,CNRS,INSERM,Pole Sinofrancais Rech Sc, Shanghai Ruijin Hosp,Int Hematol & Canc LIA,Sch M, Shanghai 200025, Peoples R China.
EM luyiming@rjh.com.cn; xdsun@sjtu.edu.cn
OI Jing, Wang/0000-0003-4477-9442; ye, jing/0000-0002-9471-3321
FU National Natural Science Foundation of China [81730026, 81425006,
   81470640, 81171846, 81270433, 81372099, 81471400, 81522017, 81671900];
   Foundation of Shanghai Jiaotong University School of Medicine for
   Translational Medicine Innovation project [15ZH4005]; Foundation of
   Shanghai Engineering Technology Research Center for Construction project
   [16dz2251500]; Foundation of the Shanghai Science and Technology
   Committee [16140900800, 11ZR1422100]; Shanghai Foundation for Basic
   Research of Science and Technology, China [13JC1404001]; Shanghai
   Municipal Education Commission -Gaofeng Clinical Medicine Grant
   [20161408]
FX This study was supported by the National Natural Science Foundation of
   China (grant numbers 81730026, 81425006, and 81470640), the Foundation
   of Shanghai Jiaotong University School of Medicine for Translational
   Medicine Innovation project (grant number 15ZH4005), the Foundation of
   Shanghai Engineering Technology Research Center for Construction project
   (grant number 16dz2251500), the Foundation of the Shanghai Science and
   Technology Committee (grant number 16140900800). Work in the JY/YL
   laboratories was supported by the National Natural Science Foundation of
   China (grant numbers 81171846, 81270433, 81372099, 81471400, 81522017,
   and 81671900), the Shanghai Foundation for Basic Research of Science and
   Technology, China (grant number 13JC1404001), the Foundation of the
   Shanghai Science and Technology Committee (grant number 11ZR1422100),
   and Shanghai Municipal Education Commission -Gaofeng Clinical Medicine
   Grant (Grant number 20161408).
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NR 48
TC 23
Z9 25
U1 0
U2 20
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD FEB 7
PY 2018
VL 9
AR 178
DI 10.1038/s41419-017-0200-7
PG 14
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA FZ2IN
UT WOS:000427401400020
PM 29415988
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Holmgaard, A
   Askou, AL
   Benckendorff, JNE
   Thomsen, EA
   Cai, YJ
   Bek, T
   Mikkelsen, JG
   Corydon, TJ
AF Holmgaard, Andreas
   Askou, Anne Louise
   Benckendorff, Josephine Natalia Esther
   Thomsen, Emil Aagaard
   Cai, Yujia
   Bek, Toke
   Mikkelsen, Jacob Giehm
   Corydon, Thomas J.
TI In Vivo Knockout of the Vegfa Gene by Lentiviral Delivery of CRISPR/Cas9
   in Mouse Retinal Pigment Epithelium Cells
SO MOLECULAR THERAPY-NUCLEIC ACIDS
LA English
DT Article
ID DOMINANT RETINITIS-PIGMENTOSA; LEBER CONGENITAL AMAUROSIS; CRISPR-CAS9
   SYSTEM; ANIMAL-MODELS; GENOME; THERAPY; CAS9; VECTORS; EXPRESSION;
   MUTATIONS
AB Virus-based gene therapy by CRISPR/Cas9-mediated genome editing and knockout may provide a new option for treatment of inherited and acquired ocular diseases of the retina. In support of this notion, we show that Streptococcus pyogenes (Sp) Cas9, delivered by lentiviral vectors (LVs), can be used in vivo to selectively ablate the vascular endothelial growth factor A (Vegfa) gene in mice. By generating LVs encoding SpCas9 targeted to Vegfa, and in parallel the fluorescent eGFP marker protein, we demonstrate robust knockout of Vegfa that leads to a significant reduction of VEGFA protein in transduced cells. Three of the designed single-guide RNAs (sgRNAs) induce in vitro indel formation at high frequencies (44%-93%). A single unilateral subretinal injection facilitates RPE-specific localization of the vector and disruption of Vegfa in isolated eGFP(+) RPE cells obtained from mice five weeks after LV administration. Notably, sgRNA delivery results in the disruption of Vegfa with an in vivo indel formation efficacy of up to 84%. Sequencing of Vegfa-specific amplicons reveals formation of indels, including 4-bp deletions and 2-bp insertions. Taken together, our data demonstrate the capacity of lentivirus-delivered SpCas9 and sgRNAs as a developing therapeutic path in the treatment of ocular diseases, including age-related macular degeneration.
C1 [Holmgaard, Andreas; Askou, Anne Louise; Benckendorff, Josephine Natalia Esther; Thomsen, Emil Aagaard; Cai, Yujia; Mikkelsen, Jacob Giehm; Corydon, Thomas J.] Aarhus Univ, Dept Biomed, Bartholin Alle 6, DK-8000 Aarhus C, Denmark.
   [Bek, Toke; Corydon, Thomas J.] Aarhus Univ Hosp, Dept Ophthalmol, DK-8000 Aarhus C, Denmark.
C3 Aarhus University; Aarhus University
RP Corydon, TJ (通讯作者)，Aarhus Univ, Dept Biomed, Bartholin Alle 6, DK-8000 Aarhus C, Denmark.
EM corydon@biomed.au.dk
RI Askou, Anne/AGW-2995-2022; Aagaard Thomsen, Emil/GLU-1406-2022; Thomsen,
   Emil Aagaard/ABB-9850-2021
OI Thomsen, Emil Aagaard/0000-0002-2685-7745; Askou, Anne
   Louise/0000-0002-5512-1796; Corydon, Thomas Juhl/0000-0003-3588-6350;
   Mikkelsen, Jacob Giehm/0000-0002-1322-3209; Bek,
   Toke/0000-0002-0409-2534
FU Faculty of Health Sciences; Danish Council for Independent Research
   [4183-00017B]; Gene Therapy Initiative Aarhus (GTI-Aarhus) - Lundbeck
   Foundation [R126-2012-12456]; Danish Eye Foundation; Aase og Ejnar
   Danielsen's Foundation; Knud and Edith Eriksen's Foundation;
   Maskinfabrikant Jochum Jensen og hustru Mette Marie Jensen f. Poulsens
   Mindelegat; Riisfort Foundation; Svend Helge Schroder og hustru Ketty
   Lydia Larsen Schroders fund
FX The authors would like to thank Tina Hindkjaer, Kamilla Zahll Hornbek,
   Christian Knudsen, and Karen Kathrine Brondum for their excellent
   technical support. Cell sorting was performed at the FACS Core Facility,
   Aarhus University, Denmark. This work was supported by the Faculty of
   Health Sciences (PhD scholarship to A.H.), the Danish Council for
   Independent Research (4183-00017B to T.J.C.), the Gene Therapy
   Initiative Aarhus (GTI-Aarhus) funded by the Lundbeck Foundation
   (R126-2012-12456 to T.J.C. and J.G.M.), the Danish Eye Foundation (to
   T.J.C.), Aase og Ejnar Danielsen's Foundation (to T.J.C.), Knud and
   Edith Eriksen's Foundation (to T.J.C.), Maskinfabrikant Jochum Jensen og
   hustru Mette Marie Jensen f. Poulsens Mindelegat (to T.J.C.), the
   Riisfort Foundation (to T.J.C.), and Svend Helge Schroder og hustru
   Ketty Lydia Larsen Schroders fund (to T.J.C.).
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NR 42
TC 36
Z9 36
U1 2
U2 25
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 DEC 15
PY 2017
VL 9
BP 89
EP 99
DI 10.1016/j.omtn.2017.08.016
PG 11
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA FQ6SJ
UT WOS:000418494000009
PM 29246327
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Zhang, YY
   Ren, S
   Liu, YC
   Gao, K
   Liu, Z
   Zhang, Z
AF Zhang, Yuanyuan
   Ren, Shu
   Liu, Yuci
   Gao, Kun
   Liu, Zheng
   Zhang, Zhou
TI Inhibition of Starvation-Triggered Endoplasmic Reticulum Stress,
   Autophagy, and Apoptosis in ARPE-19 Cells by Taurine through Modulating
   the Expression of Calpain-1 and Calpain-2
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE ARPE-19; autophagy; ER stress; apoptosis; taurine; calpain-1; calpain-2;
   age-related macular degeneration
ID ER STRESS; MITOCHONDRIAL DYSFUNCTION; CASPASE-12 ACTIVATION; OXIDATIVE
   STRESS; SURVIVAL; ROLES; P62; ROS; NEUROPROTECTION; SUPPRESSION
AB Age-related macular degeneration (AMD) is a complex disease with multiple initiators and pathways that converge on death for retinal pigment epithelial (RPE) cells. In this study, effects of taurine on calpains, autophagy, endoplasmic reticulum (ER) stress, and apoptosis in ARPE-19 cells (a human RPE cell line) were investigated. We first confirmed that autophagy, ER stress and apoptosis in ARPE-19 cells were induced by Earle's balanced salt solution (EBSS) through starvation to induce RPE metabolic stress. Secondly, inhibition of ER stress by 4-phenyl butyric acid (4-PBA) alleviated autophagy and apoptosis, and suppression of autophagy by 3-methyl adenine (3-MA) reduced the cell apoptosis, but the ER stress was minimally affected. Thirdly, the apoptosis, ER stress and autophagy were inhibited by gene silencing of calpain-2 and overexpression of calpain-1, respectively. Finally, taurine suppressed both the changes of the important upstream regulators (calpain-1 and calpain-2) and the activation of ER stress, autophagy and apoptosis, and taurine had protective effects on the survival of ARPE-19 cells. Collectively, this data indicate that taurine inhibits starvation-triggered endoplasmic reticulum stress, autophagy, and apoptosis in ARPE-19 cells by modulating the expression of calpain-1 and calpain-2.
C1 [Zhang, Yuanyuan; Ren, Shu; Liu, Yuci; Gao, Kun; Liu, Zheng; Zhang, Zhou] Shenyang Pharmaceut Univ, Dept Pharmacol, Shenyang 110016, Liaoning, Peoples R China.
C3 Shenyang Pharmaceutical University
RP Liu, Z; Zhang, Z (通讯作者)，Shenyang Pharmaceut Univ, Dept Pharmacol, Shenyang 110016, Liaoning, Peoples R China.
EM yuanyuanzhangyyz@163.com; shuyeah829@163.com; yuciiliu@163.com;
   Gaokun@sinqi.com; zhengliu@syphu.edu.cn; zhouzhang@syphu.edu.cn
RI zhang, yuanyuan/GYA-4428-2022
OI zhang, yuanyuan/0000-0002-8454-0674
FU National Natural Science Foundation of China [31270883]
FX The authors would like to thank Yanting Gu and Jian Zhao for their
   comments and suggestions for the manuscript and their helpful
   discussions for the experiments. This research was funded by the
   National Natural Science Foundation of China (Grant No. 31270883) to
   Zhou Zhang.
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NR 60
TC 32
Z9 32
U1 0
U2 13
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 OCT
PY 2017
VL 18
IS 10
AR 2146
DI 10.3390/ijms18102146
PG 16
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA FM0QL
UT WOS:000414671800130
PM 29036897
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Askou, AL
   Benckendorff, JNE
   Holmgaard, A
   Storm, T
   Aagaard, L
   Bek, T
   Mikkelsen, JG
   Corydon, TJ
AF Askou, Anne Louise
   Benckendorff, Josephine Natalia Esther
   Holmgaard, Andreas
   Storm, Tina
   Aagaard, Lars
   Bek, Toke
   Mikkelsen, Jacob Giehm
   Corydon, Thomas Juhl
TI Suppression of Choroidal Neovascularization in Mice by Subretinal
   Delivery of Multigenic Lentiviral Vectors Encoding Anti-Angiogenic
   MicroRNAs
SO HUMAN GENE THERAPY METHODS
LA English
DT Article
DE multigenic lentiviral vector; anti-angiogenesis; microRNA; VEGF; ocular
   gene therapy; CNV mouse model
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; GENE-THERAPY; MOUSE
   MODEL; IN-VITRO; EXPRESSION; PROMOTERS; EFFICACY; VIRUS;
   IMMUNODEFICIENCY
AB Lentivirus-based vectors have been used for the development of potent gene therapies. Here, application of a multigenic lentiviral vector (LV) producing multiple anti-angiogenic microRNAs following subretinal delivery in a laser-induced choroidal neovascularization (CNV) mouse model is presented. This versatile LV, carrying back-to-back RNApolII-driven expression cassettes, enables combined expression of microRNAs targeting vascular endothelial growth factor A (Vegfa) mRNA and fluorescent reporters. In addition, by including a vitelliform macular dystrophy 2 (VMD2) promoter, expression of microRNAs is restricted to the retinal pigment epithelial (RPE) cells. Six days post injection (PI), robust and widespread fluorescent signals of eGFP are already observed in the retina by funduscopy. The eGFP expression peaks at day 21 PI and persists with stable expression for at least 9 months. In parallel, prominent AsRED co-expression, encoded from the VMD2-driven microRNA expression cassette, is evident in retinal sections and flat-mounts, revealing RPE-specific expression of microRNAs. Furthermore, LV-delivered microRNAs targeting the Vegfa gene in RPE cells reduced the size of laser-induced CNV in mice 28 days PI, as a consequence of diminished VEGF levels, suggesting that LVs delivered locally are powerful tools in the development of gene therapy-based strategies for treatment of age-related macular degeneration.
C1 [Askou, Anne Louise; Benckendorff, Josephine Natalia Esther; Holmgaard, Andreas; Storm, Tina; Aagaard, Lars; Mikkelsen, Jacob Giehm; Corydon, Thomas Juhl] Aarhus Univ, Dept Biomed, Wilhelm Meyers Alle 4, DK-8000 Aarhus C, Denmark.
   [Bek, Toke; Corydon, Thomas Juhl] Aarhus Univ Hosp, Dept Ophthalmol, Aarhus, Denmark.
C3 Aarhus University; Aarhus University
RP Corydon, TJ (通讯作者)，Aarhus Univ, Dept Biomed, Wilhelm Meyers Alle 4, DK-8000 Aarhus C, Denmark.
EM corydon@biomed.au.dk
RI Askou, Anne/AGW-2995-2022
OI Bek, Toke/0000-0002-0409-2534; Corydon, Thomas Juhl/0000-0003-3588-6350;
   Storm, Tina/0000-0001-6550-4072; Mikkelsen, Jacob
   Giehm/0000-0002-1322-3209; Askou, Anne Louise/0000-0002-5512-1796
FU Lundbeck Foundation [R165-2013-15631]; Danish Council for Independent
   Research [4183-00017B]; Gene Therapy Initiative Aarhus (GTI-Aarhus) -
   Lundbeck Foundation [R126-2012-12456]; Danish Eye Foundation; Aase og
   Ejnar Danielsen's Foundation; Knud and Edith Eriksen's Foundation;
   Maskinfabrikant Jochum Jensen og hustru Mette Marie Jensen f. Poulsens
   Mindelegat; Riisfort Foundation; Synoptik-Fonden; Svend Helge Schroder
   og hustru Ketty Lydia Larsen Schroders Fond
FX The authors would like to thank Tina Hindkjaer, Kamilla Zahll Hornbek,
   and Christian Knudsen for their excellent technical support. This work
   was supported by the Lundbeck Foundation (A.L.A.; grant no.
   R165-2013-15631), the Danish Council for Independent Research (T.J.C.;
   grant no. 4183-00017B), the Gene Therapy Initiative Aarhus (GTI-Aarhus)
   funded by the Lundbeck Foundation (T.J.C., L.A. and J.G.M.; grant no.
   R126-2012-12456), the Danish Eye Foundation (T.J.C.), Aase og Ejnar
   Danielsen's Foundation (T.J.C.), Knud and Edith Eriksen's Foundation
   (T.J.C.), Maskinfabrikant Jochum Jensen og hustru Mette Marie Jensen f.
   Poulsens Mindelegat (T.J.C.), The Riisfort Foundation (T.J.C.),
   Synoptik-Fonden (T.J.C.), and Svend Helge Schroder og hustru Ketty Lydia
   Larsen Schroders Fond (T.J.C.).
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NR 51
TC 15
Z9 16
U1 0
U2 10
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1946-6536
EI 1946-6544
J9 HUM GENE THER METHOD
JI Hum. Gene Ther. Methods
PD AUG
PY 2017
VL 28
IS 4
SI SI
BP 222
EP 233
DI 10.1089/hgtb.2017.079
PN 1
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA FE0EA
UT WOS:000407892400006
PM 28817343
DA 2022-11-30
ER

PT J
AU Sapkota, K
   Kim, DH
AF Sapkota, Kishor
   Kim, Douk Hoon
TI Causes of low vision and major low-vision devices prescribed in the
   low-vision clinic of Nepal Eye Hospital, Nepal
SO ANIMAL CELLS AND SYSTEMS
LA English
DT Article
DE Cataract; low vision; nystagmus; telescope; vision impairment
ID COPENHAGEN CITY EYE; QUALITY-OF-LIFE; VISUAL IMPAIRMENT;
   ADULT-POPULATION; PREVALENCE; BLINDNESS; ACUITY
AB Visual impairment is a major public health problem. Identifying the main causes of low vision and the major low-vision devices prescribed will help to develop and implement the low-vision rehabilitation service. We find out the causes of low vision and the low-vision devices prescribed in the low-vision clinic of Nepal Eye Hospital. A retrospective cross-sectional review of all patients attending the low-vision clinic from 1 May 2009 to 31 April 2011. Patients having visual acuity less than 3/60 in the better eye with best refractive correction were excluded. Of the 137patients, the mean age was 32.53 +/- 22.90years; 71.5% were male and 67.88% were under 40. The major causes of low vision were nystagmus (30.70%), high refractive error (22.62%), cataract (15.30%), retinitis pigmentosa (15.30%) and age-related macular degeneration (13.10%); 78.10% patents were wearing glasses while telescopes were prescribed for 29.20% patients. Nystagmus, high refractive error and cataract are the main causes of low vision in Nepal. The majority of the low-vision patients seen in this clinic are of working age. Telescopes are the major low-vision device prescribed. We review approach the cause of low-vision problem in low-vision clinic Nepal Eye Hospital, Nepal.
C1 [Sapkota, Kishor] Univ Minho, Braga, Portugal.
   [Sapkota, Kishor] Nepal Eye Hosp, Kathmandu, Nepal.
   [Kim, Douk Hoon] Masan Univ, Dept Optometry, Naeseo Eup, Gyeongsangnam D, South Korea.
C3 Universidade do Minho
RP Sapkota, K (通讯作者)，Univ Minho, Braga, Portugal.; Sapkota, K (通讯作者)，Nepal Eye Hosp, Kathmandu, Nepal.
EM kishorsapkota@gmail.com
RI Sapkota, Kishor/ABD-6354-2020
CR [Anonymous], 1992, INT STAT CLASS DIS R, V1-3
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NR 20
TC 1
Z9 1
U1 0
U2 2
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1976-8354
EI 2151-2485
J9 ANIM CELLS SYST
JI Anim. Cells Syst.
PY 2017
VL 21
IS 3
BP 147
EP 151
DI 10.1080/19768354.2017.1333040
PG 5
WC Cell Biology; Zoology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Zoology
GA EY2IM
UT WOS:000403791800001
PM 30460063
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Askou, AL
   Aagaard, L
   Kostic, C
   Arsenijevic, Y
   Hollensen, AK
   Bek, T
   Jensen, TG
   Mikkelsen, JG
   Corydon, TJ
AF Askou, Anne Louise
   Aagaard, Lars
   Kostic, Corinne
   Arsenijevic, Yvan
   Hollensen, Anne Kruse
   Bek, Toke
   Jensen, Thomas Gryesten
   Mikkelsen, Jacob Giehm
   Corydon, Thomas Juhl
TI Multigenic lentiviral vectors for combined and tissue-specific
   expression of miRNA- and protein-based antiangiogenic factors
SO MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
LA English
DT Article
ID MACULAR DEGENERATION; GENE-THERAPY; CHOROIDAL NEOVASCULARIZATION; OCULAR
   NEOVASCULARIZATION; COMBINATION THERAPY; ENDOTHELIAL-CELLS; TARGETING
   VEGF; VMD2 PROMOTER; SIRNA; RNAI
AB Lentivirus-based gene delivery vectors carrying multiple gene cassettes are powerful tools in gene transfer studies and gene therapy, allowing coexpression of multiple therapeutic factors and, if desired, fluorescent reporters. Current strategies to express transgenes and microRNA (miRNA) clusters from a single vector have certain limitations that affect transgene expression levels and/or vector titers. In this study, we describe a novel vector design that facilitates combined expression of therapeutic RNA-and protein-based antiangiogenic factors as well as a fluorescent reporter from back-to-back RNApolII-driven expression cassettes. This configuration allows effective production of intron-embedded miRNAs that are released upon transduction of target cells. Exploiting such multigenic lentiviral vectors, we demonstrate robust miRNA-directed downregulation of vascular endothelial growth factor (VEGF) expression, leading to reduced angiogenesis, and parallel impairment of angiogenic pathways by codelivering the gene encoding pigment epithelium-derived factor (PEDF). Notably, subretinal injections of lentiviral vectors reveal efficient retinal pigment epithelium-specific gene expression driven by the VMD2 promoter, verifying that multigenic lentiviral vectors can be produced with high titers sufficient for in vivo applications. Altogether, our results suggest the potential applicability of combined miRNA-and protein-encoding lentiviral vectors in antiangiogenic gene therapy, including new combination therapies for amelioration of age-related macular degeneration.
C1 [Askou, Anne Louise; Aagaard, Lars; Hollensen, Anne Kruse; Jensen, Thomas Gryesten; Mikkelsen, Jacob Giehm; Corydon, Thomas Juhl] Aarhus Univ, Dept Biomed, Aarhus, Denmark.
   [Kostic, Corinne; Arsenijevic, Yvan] Univ Lausanne, Jules Gonin Eye Hosp, Dept Ophthalmol, Unit Gene Therapy & Stem Cell Biol, Lausanne, Switzerland.
   [Bek, Toke] Aarhus Univ Hosp, Dept Ophthalmol, Aarhus, Denmark.
C3 Aarhus University; University of Lausanne; Aarhus University
RP Corydon, TJ (通讯作者)，Aarhus Univ, Dept Biomed, Aarhus, Denmark.
EM corydon@biomed.au.dk
RI Askou, Anne/AGW-2995-2022
OI Mikkelsen, Jacob Giehm/0000-0002-1322-3209; Askou, Anne
   Louise/0000-0002-5512-1796; Corydon, Thomas Juhl/0000-0003-3588-6350;
   Bek, Toke/0000-0002-0409-2534; Arsenijevic, Yvan/0000-0001-6960-1291;
   Kostic, Corinne/0000-0003-1006-9733
FU Lundbeck Foundation [R44-A4289]; Gene Therapy Initiative Aarhus
   (GTI-Aarhus) - the Lundbeck Foundation [R126-2012-12456]; Danish Eye
   Foundation; Aase og Ejnar Danielsens Fond; Civilingenior Lars Andersens
   Fond; Augustinus Fonden; Synoptik Fonden; Riisfort Fonden; Provisu
   Foundation; HEALTH, Aarhus University
FX We thank Catherine Martin (UGTSCB) for her excellent technical
   assistance. Flow cytometry was performed at the FACS Core Facility, The
   Faculty of Health Sciences, Aarhus University, Denmark. This work was
   supported by the Lundbeck Foundation (Grant No. R44-A4289), Gene Therapy
   Initiative Aarhus (GTI-Aarhus) funded by the Lundbeck Foundation (Grant
   No. R126-2012-12456), The Danish Eye Foundation, Aase og Ejnar
   Danielsens Fond, Civilingenior Lars Andersens Fond, Augustinus Fonden,
   Synoptik Fonden, Riisfort Fonden, and the Provisu Foundation. A.L.A. is
   the recipient of a mobility PhD fellowship from HEALTH, Aarhus
   University.
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NR 40
TC 37
Z9 38
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
EI 2329-0501
J9 MOL THER-METH CLIN D
JI Mol.Ther.-Methods Clin. Dev.
PY 2015
VL 2
AR 14064
DI 10.1038/mtm.2014.64
PG 11
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA V46YE
UT WOS:000209918700008
PM 26052532
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Vargis, E
   Peterson, CB
   Morrell-Falvey, JL
   Retterer, ST
   Collier, CP
AF Vargis, Elizabeth
   Peterson, Cristen B.
   Morrell-Falvey, Jennifer L.
   Retterer, Scott T.
   Collier, Charles Patrick
TI The effect of retinal pigment epithelial cell patch size on growth
   factor expression
SO BIOMATERIALS
LA English
DT Article
DE Microcontact printing; Retinal pigment epithelial; Tight junctions;
   VEGF; In vitro model; Micropatterning
ID MACULAR DEGENERATION; DISEASE; ATROPHY
AB The spatial organization of retinal pigment epithelial (RPE) cells grown in culture was controlled using micropatterning techniques in order to examine the effect of patch size on cell health and differentiation. Understanding this effect is a critical step in the development of multiplexed high throughput fluidic assays and provides a model for replicating disease states associated with the deterioration of retinal tissue during age-related macular degeneration (AMD). Microcontact printing of fibronectin on polystyrene and glass substrates was used to promote cell attachment, forming RPE patches of controlled size and shape. These colonies mimic the effect of atrophy and loss-of-function that occurs in the retina during degenerative diseases such as AMD. After 72 h of cell growth, levels of vascular endothelial growth factor (VEGF), an important biomarker of AMD, were measured. Cells were counted and morphological indicators of cell viability and tight junction formation were assessed via fluorescence microscopy. Up to a twofold increase of VEGF expression per cell was measured as colony size decreased, suggesting that the local microenvironment of, and connections between, RPE cells influences growth factor expression leading to the initiation and progression of diseases such as AMD. (c) 2014 Elsevier Ltd. All rights reserved.
C1 [Vargis, Elizabeth; Retterer, Scott T.; Collier, Charles Patrick] Oak Ridge Natl Lab, Ctr Nanophase Mat Sci, Oak Ridge, TN 37831 USA.
   [Vargis, Elizabeth] Univ Tennessee, Joint Inst Biol Sci, Knoxville, TN 37996 USA.
   [Peterson, Cristen B.; Morrell-Falvey, Jennifer L.; Retterer, Scott T.] Oak Ridge Natl Lab, Biosci Div, Oak Ridge, TN 37831 USA.
C3 United States Department of Energy (DOE); Oak Ridge National Laboratory;
   Center for Nanophase Materials Sciences; University of Tennessee System;
   University of Tennessee Knoxville; United States Department of Energy
   (DOE); Oak Ridge National Laboratory
RP Retterer, ST (通讯作者)，Oak Ridge Natl Lab, Ctr Nanophase Mat Sci, Oak Ridge, TN 37831 USA.
EM rettererst@ornl.gov; colliercp@ornl.gov
RI Collier, Charles/C-9206-2016; Vargis, Elizabeth/M-8021-2018;
   Morrell-Falvey, Jennifer L/A-6615-2011; Retterer, Scott/A-5256-2011
OI Collier, Charles/0000-0002-8198-793X; Vargis,
   Elizabeth/0000-0003-3141-9317; Morrell-Falvey, Jennifer
   L/0000-0002-9362-7528; Retterer, Scott/0000-0001-8534-1979
FU Scientific User Facilities Division,Office of Basic Energy Sciences,
   U.S. Department of Energy
FX A portion of this research was conducted at the Center for Nanophase
   Materials Sciences, which is sponsored at Oak Ridge National Laboratory
   by the Scientific User Facilities Division, Office of Basic Energy
   Sciences, U.S. Department of Energy.
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NR 25
TC 12
Z9 12
U1 0
U2 24
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
EI 1878-5905
J9 BIOMATERIALS
JI Biomaterials
PD APR
PY 2014
VL 35
IS 13
BP 3999
EP 4004
DI 10.1016/j.biomaterials.2014.01.016
PG 6
WC Engineering, Biomedical; Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Materials Science
GA AF1NQ
UT WOS:000334481000008
PM 24485792
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Chen, J
   Pikuleva, IA
   Turko, IV
AF Chen, Junjun
   Pikuleva, Irina A.
   Turko, Illarion V.
TI Mass spectrometry quantification of PICALM and AP180 in human frontal
   cortex and neural retina
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
DE QconCAT; Multiple reaction monitoring; PICALM; AP180; Alzheimer disease;
   Neural retina
ID GENOME-WIDE ASSOCIATION; ALZHEIMERS-DISEASE; ABSOLUTE QUANTIFICATION;
   MACULAR DEGENERATION; INTERNAL STANDARD; PROTEINS; CLATHRIN; PROTEOMICS;
   ISOFORMS; PLASMA
AB Recent genome-wide association studies have suggested that endocytic factors, such as phosphatidylinositol-binding clathrin assembly protein (PICALM), may be implicated in the development of Alzheimer disease (AD). The cellular functions of PICALM are in line with this possibility: (i) PICALM is involved in regulation of amyloid-beta levels and (ii) PICALM is important for a presynaptic function, which is diminished in AD. To facilitate the analysis of PICALM, we developed a quantitative method to assess the expression level of PICALM in various biological samples. For this purpose, a stable isotope-labeled quantification concatamer (QconCAT) of PICALM was designed, expressed, purified, and characterized. The PICALM QconCAT was first used as an internal standard in a multiple reaction monitoring assay to measure PICALM concentrations in the human frontal cortex, a tissue strongly affected by AD. A second endocytic factor that is highly homologous to PICALM and also functions in clathrin-mediated endocytosis, clathrin coat assembly protein AP180, was quantified as well. Because age-related macular degeneration shares several clinical and pathological features with AD, the measurements were then extended to human normal neural retina. Overall, the developed method is suitable for PICALM and AP180 quantitative analysis in various biological samples of interest. Published by Elsevier Inc.
C1 [Chen, Junjun; Turko, Illarion V.] Univ Maryland, Inst Biosci & Biotechnol Res, Rockville, MD 20850 USA.
   [Chen, Junjun; Turko, Illarion V.] Natl Inst Stand & Technol, Biomol Measurement Div, Gaithersburg, MD 20899 USA.
   [Pikuleva, Irina A.] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
C3 National Institute of Standards & Technology (NIST) - USA; Case Western
   Reserve University
RP Turko, IV (通讯作者)，Natl Inst Stand & Technol, Biomol Measurement Div, Gaithersburg, MD 20899 USA.
EM iturko@umd.edu
OI Pikuleva, Irina/0000-0001-9742-6232
FU National Institutes of Health [EY018383]; Research to Prevent Blindness;
   NATIONAL EYE INSTITUTE [R01EY018383] Funding Source: NIH RePORTER
FX This work was supported in part by National Institutes of Health Grant
   EY018383 (to I.A.P.). I.A.P. is a recipient of the Jules and Doris Stein
   Professorship from Research to Prevent Blindness. We thank Dr. S. Huang
   for the retinal assessments; Dr. R. Reem, Dr. S. Omarova, and Dr. N.
   Mast for the isolation of the retinal samples; and Dr. A. Szakal for
   helpful discussions and critical reviewing the manuscript. Certain
   commercial materials, instruments, and equipment are identified in this
   article to specify the experimental procedure as completely as possible.
   In no case does such identification imply a recommendation or
   endorsement by the National Institute of Standards and Technology nor
   does it imply that the materials, instruments, or equipment identified
   are necessarily the best available for the purpose.
CR Anderson L, 2006, MOL CELL PROTEOMICS, V5, P573, DOI 10.1074/mcp.M500331-MCP200
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NR 24
TC 4
Z9 4
U1 0
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0003-2697
EI 1096-0309
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD NOV 15
PY 2013
VL 442
IS 2
BP 253
EP 258
DI 10.1016/j.ab.2013.08.005
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
   Chemistry, Analytical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA 239ZN
UT WOS:000326064600020
PM 23954523
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Maa, AY
   Evans, C
   Delaune, W
   Lynch, MG
AF Maa, April Y.
   Evans, Centrael
   Delaune, William
   Lynch, Mary G.
TI Veteran Eye Disease After Eligibility Reform: Prevalence and
   Characteristics
SO MILITARY MEDICINE
LA English
DT Article
ID OPEN-ANGLE GLAUCOMA; UNITED-STATES; ADULTS
AB Purpose: To determine the prevalence of eye disease in new "routine" eye patients at the Atlanta Veteran Affairs Medical Center. Design: Retrospective chart review of all new eye patients seen in the Atlanta Veteran Affairs Medical Center Comprehensive Eye Clinic over a 2-month period (January 1, 2008-February 28, 2008). Participants: 691 charts met inclusion criteria, with 33 charts excluded for insufficient documentation in the medical record. This left a total of 658 charts for the study. Methods: Charts were reviewed for the-following information: demographic data, vision, ocular diagnoses (International Classification of Diseases, 9th Revision, Clinical Modification codes), and planned minor/laser/incisional surgical procedures. Additional data collected included whether glasses were prescribed and legal blindness. Main Outcome Measures: Vision-threatening ocular diagnoses and need for minor/laser/incision surgery were tabulated. Results: There was a very high prevalence of potentially blinding disease in this population of new "routine" eye patients. About 63.4% of veterans were diagnosed with at least one ocular diagnosis other than refractive error; 25% had glaucoma or were suspects, 6% had cataracts, 5% had age-related macular degeneration, and 8% required a surgical procedure. Conclusion: The rate of ocular pathology is high in the veteran population.
C1 [Maa, April Y.; Lynch, Mary G.] Atlanta VA Med Ctr, Dept Surg Serv, Div Ophthalmol, Atlanta, GA 30033 USA.
   [Evans, Centrael] Emory Univ, Sch Med, Atlanta, GA 30322 USA.
   [Delaune, William] Atlanta VA Med Ctr, Rehabil Res Div, Dept Res & Dev, Atlanta, GA 30033 USA.
C3 US Department of Veterans Affairs; Veterans Health Administration (VHA);
   Atlanta VA Health Care System; Atlanta VA Medical Center; Emory
   University; US Department of Veterans Affairs; Veterans Health
   Administration (VHA); Atlanta VA Health Care System; Atlanta VA Medical
   Center
RP Maa, AY (通讯作者)，Atlanta VA Med Ctr, Dept Surg Serv, Div Ophthalmol, 1670 Clairmont Rd MC 112E, Atlanta, GA 30033 USA.
CR CDC (Cent. Dis. Control Prev.), 2004, MMWR-MORBID MORTAL W, V53, P1069
   Congdon N, 2004, ARCH OPHTHALMOL-CHIC, V122, P487
   Department of Veterans Affairs Office of ADUSH for Policy and Planning, 2011, 2011 SURV VET ENR HL
   Federal Government, 2010, US CENS BUR REP
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   United States Department of Veteran Affairs, HISTORY
   Veterans Health Administration, NAT KLF DAT
   Vitale S, 2006, JAMA-J AM MED ASSOC, V295, P2158, DOI 10.1001/jama.295.18.2158
NR 14
TC 4
Z9 4
U1 0
U2 0
PU ASSOC MILITARY SURG US
PI BETHESDA
PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA
SN 0026-4075
EI 1930-613X
J9 MIL MED
JI Milit. Med.
PD JUL
PY 2013
VL 178
IS 7
BP 811
EP 815
DI 10.7205/MILMED-D-12-00537
PG 5
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA AN7UA
UT WOS:000340805300018
PM 23820357
OA Bronze
DA 2022-11-30
ER

PT J
AU Zhou, P
   Ye, HF
   Jiang, YX
   Yang, J
   Zhu, XJ
   Sun, XH
   Luo, Y
   Dou, GR
   Wang, YS
   Lu, Y
AF Zhou, Peng
   Ye, Hong-Fei
   Jiang, Yong-Xiang
   Yang, Jin
   Zhu, Xiang-Jia
   Sun, Xing-Huai
   Luo, Yi
   Dou, Guo-Rui
   Wang, Yu-Sheng
   Lu, Yi
TI alpha A Crystallin May Protect against Geographic Atrophy-Meta-Analysis
   of Cataract vs. Cataract Surgery for Geographic Atrophy and Experimental
   Studies
SO PLOS ONE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; RETINAL-PIGMENT EPITHELIUM; TOLL-LIKE
   RECEPTOR-3; HEAT-SHOCK-PROTEIN; MACULAR DEGENERATION; EYE DISEASE; LENS;
   RISK; PROGRESSION; ZEBULARINE
AB Background: Cataract and geographic atrophy (GA, also called advanced "dry" age-related macular degeneration) are the two major causes of visual impairment in the developed world. The association between cataract surgery and the development of GA was controversial in previous studies.
   Methods/Principal Findings: We performed a meta-analysis by pooling the current evidence in literature and found that cataract is associated with an increased risk of geographic atrophy with a summary odds ratio (OR) of 3.75 (95% CI: 95% CI: 1.84-7.62). However, cataract surgery is not associated with the risk of geographic atrophy (polled OR = 3.23, 95% CI: 0.63-16.47). Further experiments were performed to analyze how the alpha A-crystallin, the major component of the lens, influences the development of GA in a mouse model. We found that the alpha A-crystallin mRNA and protein expression increased after oxidative stress induced by NaIO3 in immunohistochemistry of retinal section and western blot of posterior eyecups. Both functional and histopathological evidence confirmed that GA is more severe in alpha A-crystallin knockout mice compared to wild-type mice.
   Conclusions: Therefore, alpha A-crystallin may protect against geographic atrophy. This study provides a better understanding of the relationship between cataract, cataract surgery, and GA.
C1 [Zhou, Peng; Ye, Hong-Fei; Jiang, Yong-Xiang; Yang, Jin; Zhu, Xiang-Jia; Sun, Xing-Huai; Luo, Yi; Lu, Yi] Fudan Univ, Dept Ophthalmol, Eye & ENT Hosp, Shanghai 200433, Peoples R China.
   [Dou, Guo-Rui; Wang, Yu-Sheng] Fourth Mil Med Univ, Dept Ophthalmol, Xijing Hosp, Xian 710032, Peoples R China.
C3 Fudan University; Air Force Military Medical University
RP Zhou, P (通讯作者)，Fudan Univ, Dept Ophthalmol, Eye & ENT Hosp, Shanghai 200433, Peoples R China.
EM luyi0705@yahoo.com.cn
RI Zhou, Peng/C-6054-2008
OI Zhou, Peng/0000-0002-1744-5167; Ye, Hongfei/0000-0001-6129-8507
FU National Basic Research Program of China (973 Program) [2011CB510200];
   National Natural Science Foundation of China (NSFC) [81070740, 81070717]
FX This research was supported by grant from the National Basic Research
   Program of China (973 Program) No. 2011CB510200, National Natural
   Science Foundation of China (NSFC) No. 81070740 and No. 81070717. The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
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NR 34
TC 9
Z9 9
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 AUG 20
PY 2012
VL 7
IS 8
AR e43173
DI 10.1371/journal.pone.0043173
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 991WJ
UT WOS:000307733800050
PM 22916220
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Kiernan, DF
   Mieler, WF
AF Kiernan, Daniel F.
   Mieler, William F.
TI Intraocular corticosteroids for posterior segment disease: 2012 update
SO EXPERT OPINION ON PHARMACOTHERAPY
LA English
DT Review
DE choroidal neovascularization (CNV); clinical trials; cystoid macular
   edema (CME); dexamethasone; diabetic macular edema (DME); fluocinolone
   acetonide; intravitreal implant; posterior uveitis; retinal vein
   occlusion; triamcinolone acetonide
ID INTRAVITREAL TRIAMCINOLONE ACETONIDE; RETINAL-VEIN-OCCLUSION; DIABETIC
   MACULAR EDEMA; ENDOTHELIAL GROWTH-FACTOR; INTERNAL LIMITING MEMBRANE;
   PARS-PLANA VITRECTOMY; DRUG-DELIVERY SYSTEM; FLUOCINOLONE ACETONIDE;
   CHOROIDAL NEOVASCULARIZATION; PHOTODYNAMIC THERAPY
AB Introduction: Diabetic macular edema (DME), cystoid macular edema (CME), age-related macular degeneration (AMD), retinal vascular occlusion (RVO) and uveitis are responsible for severe visual impairment worldwide. In some patients with these conditions, treatment with intraocular corticosteroids may be beneficial. Although off-label use of these agents has occurred for many years, novel agents including preservative-free and sustained-release intravitreal implants are currently being studied in clinical trials (CTs).
   Areas covered: This paper reviews the use of CTs for vitreoretinal (VR) diseases including choroidal neovascularization, CME, DME, RVO and posterior uveitis. It also discusses the use of corticosteroids for treating VR disease, including dexamethasone, fluocinolone acetonide, intravitreal implants and triamcinolone acetonide.
   Expert opinion: Used alone, intravitreal corticosteroids may benefit disorders such as DME, RVO and uveitis compared with standard therapy. Cases of exudative AMD non-responsive to standard treatment may benefit from combination therapy, including usage of intravitreal corticosteroid injections. Intraoperative use of these agents may aid visualization of retinal structures. Sustained-release intraocular implants have been approved for posterior uveitis and RVO associated with macular edema. In spite of this, most intraocular corticosteroids have a limited duration of action along with significant side effects, including cataract and glaucoma. Currently, intravitreal corticosteroid usage for DME is considered off-label.
C1 [Mieler, William F.] Univ Illinois, Illinois Eye & Ear Infirm, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA.
   [Kiernan, Daniel F.] Rockville Ctr, Rockville, NY USA.
C3 University of Illinois System; University of Illinois Chicago;
   University of Illinois Chicago Hospital
RP Mieler, WF (通讯作者)，Univ Illinois, Illinois Eye & Ear Infirm, Dept Ophthalmol & Visual Sci, 1855 W Taylor St, Chicago, IL 60612 USA.
EM wmieler@uic.edu
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NR 96
TC 14
Z9 15
U1 0
U2 11
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1465-6566
EI 1744-7666
J9 EXPERT OPIN PHARMACO
JI Expert Opin. Pharmacother.
PD AUG
PY 2012
VL 13
IS 12
BP 1679
EP 1694
DI 10.1517/14656566.2012.690736
PG 16
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 975PZ
UT WOS:000306524600003
PM 22783878
DA 2022-11-30
ER

PT J
AU Hemmer, M
   Kempen, I
   de Tullio, P
   Frankenne, F
   Lambert, V
   Blacher, S
   Bueb, JL
   Foidart, JM
   Noel, A
   Tschirhart, E
   Pirotte, B
AF Hemmer, Marc
   Kempen, Isabelle
   de Tullio, Pascal
   Frankenne, Francis
   Lambert, Vincent
   Blacher, Silvia
   Bueb, Jean-Luc
   Foidart, Jean-Michel
   Noel, Agnes
   Tschirhart, Eric
   Pirotte, Bernard
TI New Biological Investigations on 3-Bromophenyl
   6-Acetoxymethyl-2-oxo-2H-1-Benzopyran-3-Carboxylate as Anti-angiogenic
   Agent
SO DRUG DEVELOPMENT RESEARCH
LA English
DT Article
DE angiogenesis; cancer; age-related macular degeneration; anti-angiogenic
   agents; coumarin derivatives
ID ACTIVATOR INHIBITOR TYPE-1; CANCER-CELL INVASION; CHOROIDAL
   NEOVASCULARIZATION; TUMOR ANGIOGENESIS; MATRIX METALLOPROTEINASES;
   ALPHA-CHYMOTRYPSIN; RAT AORTA; GROWTH; DERIVATIVES; METASTASIS
AB The development of blood vessels inside tumors is required to provide the nutrients and oxygen needed for tumor growth and to allow the spread of cancer cells at a distance to form metastasis. Angiogenesis is also implicated in ocular diseases like age-related macular degeneration. The present work describes the potential anti-angiogenic properties of a coumarinic derivative, 3-bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate (IK9), previously described as a potent inhibitor of HT 1080 fibrosarcoma cell invasion in vitro and tumor growth in vivo. In vivo, ex vivo, and in vitro models were used to delineate the anti-angiogenic properties of IK9. The anti-angiogenic effect of IK9 was demonstrated in vivo in a choroidal neovascularization mice model and additionally ex vivo in a rat aortic ring assay where it was more active than the known matrix metalloproteinase inhibitor Ro 28-2653. IK9 did not affect apoptosis, proliferation, or endothelial cell invasiveness in vitro. These findings suggest a complex mechanism of action of the compound via direct or indirect effects on endothelial cell properties. This study identifies IK9 as a new potent inhibitor of angiogenesis and suggests its potential use as a therapeutic agent. Drug Dev Res 71:209-218, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Hemmer, Marc; Kempen, Isabelle; de Tullio, Pascal; Noel, Agnes; Pirotte, Bernard] Univ Liege, Ctr Interfac Rech Medicament, Lab Chim Pharmaceut, Drug Res Ctr, B-4000 Liege, Belgium.
   [Frankenne, Francis; Lambert, Vincent; Blacher, Silvia; Foidart, Jean-Michel; Noel, Agnes] Univ Liege, Lab Tumor & Dev Biol, GIGA Canc, B-4000 Liege, Belgium.
   [Hemmer, Marc; Bueb, Jean-Luc; Tschirhart, Eric] Univ Luxembourg, Life Sci Res Unit, L-1511 Luxembourg, Grand Duchy Lux, Luxembourg.
C3 University of Liege; University of Liege; University of Luxembourg
RP Hemmer, M (通讯作者)，Univ Liege, Ctr Interfac Rech Medicament, Lab Chim Pharmaceut, Drug Res Ctr, 1 Ave Hop, B-4000 Liege, Belgium.
EM mhemmer@student.ulg.ac.be
RI De Tullio, Pascal/ABE-5585-2021
OI Noel, Agnes/0000-0002-7670-6179
FU FNR, Luxembourg; FNRS, Belgium; European FP7 project (MicroEnviMet)
FX Grant sponsors: FNR, Luxembourg; FNRS, Belgium; European FP7 project
   (MicroEnviMet).
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NR 38
TC 0
Z9 1
U1 0
U2 8
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0272-4391
EI 1098-2299
J9 DRUG DEVELOP RES
JI Drug Dev. Res.
PD MAY
PY 2010
VL 71
IS 3
BP 209
EP 218
DI 10.1002/ddr.20364
PG 10
WC Chemistry, Medicinal; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 604LY
UT WOS:000278281700005
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Haapasalo, K
   Jarva, H
   Siljander, T
   Tewodros, W
   Vuopio-Varkila, J
   Jokiranta, TS
AF Haapasalo, Karita
   Jarva, Hanna
   Siljander, Tuula
   Tewodros, Wezenet
   Vuopio-Varkila, Jaana
   Jokiranta, T. Sakari
TI Complement factor H allotype 402H is associated with increased C3b
   opsonization and phagocytosis of Streptococcus pyogenes
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID HEMOLYTIC-UREMIC SYNDROME; HEPARIN-BINDING DOMAIN; SHORT CONSENSUS
   REPEAT; GROUP-A STREPTOCOCCI; C-REACTIVE PROTEIN; RCA GENE-CLUSTER;
   MACULAR DEGENERATION; ALTERNATIVE PATHWAY; C3B/C4B RECEPTOR; SURFACE
   PROTEIN
AB The main virulence factor of group A streptococcus (GAS), M protein, binds plasma complement regulators factor H (FH) and FH-like protein 1 (FHL-1) leading to decreased opsonization. The M protein binding site on FH is within domain 7 in which also the age-related macular degeneration (AMD)-associated polymorphism Y402H is located. We studied if FH allotypes 402H and 402Y have different binding affinities to GAS. Plasma-derived FH allotype 402H and its recombinant fragment FH5-7(402H) showed decreased binding to several GAS strains. Growth of GAS in human blood taken from FH(402H) homozygous individuals was decreased when compared with blood taken from FH(402Y) homozygous individuals. The effect of the allotype 402H can be explained by combining the previous M protein mutagenesis data and the recently published crystal structure of FH6-8. In conclusion the data indicate that the AMD-associated allotype 402H leads to diminished binding of FH to GAS and increased opsonophagocytosis of the bacteria in blood. These results suggest that the homozygous presence of the allele 402H could be associated with decreased risk for severe GAS infections offering an explanation for the high frequency of the allele despite its association with visual impairment.
C1 [Haapasalo, Karita; Jarva, Hanna; Jokiranta, T. Sakari] Univ Helsinki, Dept Bacteriol & Immunol, Haartman Inst, Helsinki, Finland.
   [Haapasalo, Karita; Jarva, Hanna; Jokiranta, T. Sakari] Univ Helsinki, HUSLAB, Helsinki, Finland.
   [Siljander, Tuula; Vuopio-Varkila, Jaana] Natl Publ Hlth Inst, Dept Bacterial & Inflammatory Dis, Helsinki, Finland.
   [Tewodros, Wezenet] Spartan Hlth Sci Univ, Spartan Med Sch, St Lucia, St Lucia.
C3 University of Helsinki; University of Helsinki; Finland National
   Institute for Health & Welfare
RP Jokiranta, TS (通讯作者)，Univ Helsinki, Dept Bacteriol & Immunol, Haartman Inst, Helsinki, Finland.
EM sakari.jokiranta@helsinki.fi
RI Jokiranta, T. Sakari/F-1906-2011; Tewodros, Wezenet/AAR-2118-2020
OI Haapasalo, Karita/0000-0002-9619-625X; Jarva, Hanna/0000-0002-9154-354X
FU Academy of Finland [201506, 202529]; Helsinki University Central
   Hospital Funds; The Sigrid JusElius Foundation; The Finnish Cultural
   Foundation
FX We thank Marjatta Ahonen, Kirsti Widing, Eine Virolainen and Aila
   Soininen for kind help and excellent technical assistance. This work was
   financially supported by the Academy of Finland (projects 201506 and
   202529), The Helsinki University Central Hospital Funds, The Sigrid
   JusElius Foundation and The Finnish Cultural Foundation.
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NR 54
TC 40
Z9 40
U1 0
U2 3
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0950-382X
EI 1365-2958
J9 MOL MICROBIOL
JI Mol. Microbiol.
PD NOV
PY 2008
VL 70
IS 3
BP 583
EP 594
DI 10.1111/j.1365-2958.2008.06347.x
PG 12
WC Biochemistry & Molecular Biology; Microbiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Microbiology
GA 392LU
UT WOS:000262305000005
PM 18627465
DA 2022-11-30
ER

PT J
AU Schmidt, KG
   Bergert, H
   Funk, RHW
AF Schmidt, K. -G.
   Bergert, H.
   Funk, R. H. W.
TI Neurodegenerative diseases of the retina and potential for protection
   and recovery
SO CURRENT NEUROPHARMACOLOGY
LA English
DT Review
DE neurodegeneration; neuroprotection; retina; glaucoma; diabetic
   retinopathy; age-related macular degeneration; retinal ganglion cells
ID GLYCATION END-PRODUCTS; GANGLION-CELL DEATH; OCULAR PULSE AMPLITUDE;
   ASPARTATE RECEPTOR ANTAGONISM; AMYLOID PRECURSOR PROTEIN; ELEVATED
   GLUTAMATE LEVELS; ENDOTHELIAL GROWTH-FACTOR; LOW-TENSION GLAUCOMA;
   OPEN-ANGLE GLAUCOMA; CROSS-LINK BREAKER
AB Recent advances in our understanding of the mechanisms in the cascade of events resulting in retinal cell death in ocular pathologies like glaucoma, diabetic retinopathy and age-related macular degeneration led to the common descriptive term of neurodegenerative diseases of the retina. The final common pathophysiologic pathway of these diseases includes a particular form of metabolic stress, resulting in an insufficient supply of nutrients to the respective target structures (optic nerve head, retina). During metabolic stress, glutamate is released initiating the death of neurones containing ionotropic glutamate (N-methyl-D-aspartat, NMDA) receptors present on ganglion cells and a specific type of amacrine cells. Experimental studies demonstrate that several drugs reduce or prevent the death of retinal neurones deficient of nutrients. These agents generally block NMDA receptors to prevent the action of glutamate or halt the subsequent pathophysiologic cycle resulting in cell death. The major causes for cell death following activation of NMDA receptors are the influx of calcium and sodium into cells, the generation of free radicals linked to the formation of advanced glycation end-products (AGEs) and/or advanced lipoxidation endproducts (ALEs) as well as defects in the mitochondrial respiratory chain. Substances preventing these cytotoxic events are considered to be potentially neuroprotective.
C1 [Schmidt, K. -G.] Dept Ophthalmol, D-82319 Starnberg, Germany.
   [Bergert, H.] Univ Dresden, Dept Surg, D-01307 Dresden, Germany.
   [Funk, R. H. W.] Univ Dresden, Dept Anat, D-01307 Dresden, Germany.
C3 Technische Universitat Dresden; Technische Universitat Dresden
RP Schmidt, KG (通讯作者)，Dept Ophthalmol, Josef Jagerhuberstr 7, D-82319 Starnberg, Germany.
EM k.g.schmidt@gmx.de
RI Funk, Richard HW/I-1780-2013
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   [No title captured]
NR 206
TC 69
Z9 75
U1 1
U2 6
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 1570-159X
EI 1875-6190
J9 CURR NEUROPHARMACOL
JI Curr. Neuropharmacol.
PD JUN
PY 2008
VL 6
IS 2
BP 164
EP 178
DI 10.2174/157015908784533851
PG 15
WC Neurosciences; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 311RM
UT WOS:000256617300006
PM 19305795
OA Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Krishna, Y
   Sheridan, CM
   Kent, DL
   Grierson, I
   Williams, RL
AF Krishna, Yamini
   Sheridan, Carl M.
   Kent, David L.
   Grierson, Ian
   Williams, Rachel L.
TI Polydimethylsiloxane as a substrate for retinal pigment epithelial cell
   growth
SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
LA English
DT Article
DE age-related macular degeneration; transplantation; artificial
   substrates; gas plasma treatment and surface modification
ID HUMAN ENDOTHELIAL-CELLS; PLASMA-TREATED PET; PTFE IN-VITRO; MACULAR
   DEGENERATION; ADHESION MOLECULES; MONOCYTE ADHESION; THIN-FILMS;
   TRANSPLANTATION; EXPRESSION; SURFACES
AB Retinal pigment epithelial (RPE) cell transplantation represents potential treatment for age-related macular degeneration (AMD). Because delivery of isolated cells can cause serious complications, it is necessary to develop a suitable transplant membrane that could support an intact functioning RPE monolayer. Polydimethylsiloxane (PDMS) possesses the physical properties required for a transplanting device and is widely used clinically. We have investigated the use of PDMS as a potential surface for the growth of healthy RPE monolayers. PDMS discs were surface modified by air and ammonia gas plasma treatments. Dynamic contact angles were measured to determine the changes in wettability. Human ARPE-19 cells were seeded onto untreated and treated samples. Cell number, morphology and monolayer formation, cytotoxicity, and phagocytosis of photoreceptor outer segments (POS) were assessed at set time-points. Air plasma treatment increased the wettability of PDMS. This significantly enhanced cell growth, reaching confluence by day 7. Immunofluorescence revealed well-defined actin staining, monolayer formation, and high cell v ability on air plasma treated and untreated surfaces, and to a lesser extent, on ammonia plasma treated. Furthermore, RPE monolayers were able to demonstrate phagocytosis of POS in a time-dependent manner similar to control. PDMS can support an intact functional monolayer Of healthy differentiated RPE cells. (c) 2006 Wiley Periodicals, Inc.
C1 Univ Liverpool, Sch Clin Sci, Dept Ophthalmol, Liverpool L69 3GA, Merseyside, England.
   Aut Even Hosp, Kilkenny, Ireland.
   Univ Liverpool, Sch Clin Sci, Dept Clin Engn, Liverpool L69 3GA, Merseyside, England.
C3 University of Liverpool; University of Liverpool
RP Krishna, Y (通讯作者)，Univ Liverpool, Sch Clin Sci, Dept Ophthalmol, Liverpool L69 3GA, Merseyside, England.
EM y.krishna@liverpool.ac.uk
RI Sheridan, Carl/AAH-3607-2021
OI Sheridan, Carl/0000-0003-0100-9587; Williams,
   Rachel/0000-0002-1954-0256; , Yamini/0000-0001-5067-3682
CR BELAFORMANEK C, 2002, J CATARACT REFR SURG, V28, P50
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NR 33
TC 27
Z9 29
U1 0
U2 9
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1549-3296
J9 J BIOMED MATER RES A
JI J. Biomed. Mater. Res. Part A
PD MAR 1
PY 2007
VL 80A
IS 3
BP 669
EP 678
DI 10.1002/jbm.a.30953
PG 10
WC Engineering, Biomedical; Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Materials Science
GA 135DM
UT WOS:000244134300016
PM 17058209
DA 2022-11-30
ER

PT J
AU Brunk, UT
   Terman, A
AF Brunk, UT
   Terman, A
TI Lipofuscin: Mechanisms of age-related accumulation and influence on cell
   function
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Review
DE age pigment; aging; autophagocytosis; centrophenoxine; free radicals;
   lysosomes; mitochondria; oxidative stress
ID LYSOSOMAL DEGRADATIVE FUNCTIONS; HUMAN FIBROBLASTS; OXIDATIVE STRESS;
   EPITHELIAL-CELLS; BATTEN-DISEASE; CATHEPSIN-B; ALZHEIMERS-DISEASE;
   RETINOID COMPONENT; CARDIAC LIPOFUSCIN; RAT-BRAIN
AB The accumulation of lipofuscin within postmitotic cells is a recognized hallmark of aging occuring with a rate inversely related to longevity. Lipofuscin is an intralysosomal, polymeric substance, primarily composed of cross-linked protein residues, formed due to iron-catalyzed oxidative processes. Because it is undegradable and cannot be removed via exocytosis, lipofuscin accumulation in postmitotic cells is inevitable, whereas proliferative cells efficiently dilute it during division. The rate of lipofuscin formation can be experimentally manipulated. In cell culture models, oxidative stress (e.g., exposure to 40% ambient oxygen or low molecular weight iron) promotes lipofuscin accumulation, whereas growth at 8% oxygen and treatment with antioxidants or iron-chelators diminish it. Lipofuscin is a fluorochrome and may sensitize lysosomes to visible light, a process potentially important for the pathogenesis of age-related macular degeneration. Lipofuscin-associated iron sensitizes lysosomes to oxidative stress, jeopardizing lysosomal stability and causing apoptosis due to release of lysosomal contents. Lipofuscin accumulation may also diminish autophagocytotic capacity by acting as a sink for newly produced lysosomal enzymes and, therefore, interfere with recycling of cellular components. Lipofuscin, thus, may be much more directly related to cellular degeneration at old age than was hitherto believed. (C) 2002 Elsevier Science Inc.
C1 Linkoping Univ, Fac Hlth Sci, Div Pathol 2, Linkoping, Sweden.
C3 Linkoping University
RP Brunk, UT (通讯作者)，Linkoping Univ Hosp, Div Pathol 2, SE-58185 Linkoping, Sweden.
EM ulf.brunk@pat.liu.se
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NR 75
TC 639
Z9 669
U1 4
U2 83
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 SEP 1
PY 2002
VL 33
IS 5
BP 611
EP 619
AR PII S0891-5849(02)00959-0
DI 10.1016/S0891-5849(02)00959-0
PG 9
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 588BQ
UT WOS:000177680900006
PM 12208347
DA 2022-11-30
ER

PT J
AU Venkatesh, P
   Takkar, B
   Temkar, S
AF Venkatesh, Pradeep
   Takkar, Brijesh
   Temkar, Shreyas
TI Clinical manifestations of pachychoroid may be secondary to pachysclera
   and increased scleral rigidity
SO MEDICAL HYPOTHESES
LA English
DT Article
DE Pachychoroid; Polypoidal choroidal vasculopathy; Central serous
   chorioretinopathy; Scleral thickness
ID OPTICAL COHERENCE TOMOGRAPHY
AB Current imaging advancements have led to emergence of pachychoroid as an association of important vision threatening diseases like chronic serous chorioretinopathy and polypoidal choroidal vasculopathy. While the precise relation between thick choroid and such disorder is being investigated, the etiology behind pachychoroid remains elusive. We hypothesize pachychoroid to be a resultant of impeded vascular outflow due to thick sclera and increased scleral rigidity. We discuss our hypothesis in the perspective of other choroidal manifestations of anomalously thick scleral structure.
C1 [Venkatesh, Pradeep; Takkar, Brijesh; Temkar, Shreyas] All India Inst Med Sci, Dr RP Ctr Ophthalm Sci, Retina & Uvea Serv, New Delhi 110029, India.
C3 All India Institute of Medical Sciences (AIIMS) New Delhi; Dr. Rajendra
   Prasad Centre for Ophthalmic Sciences
RP Venkatesh, P (通讯作者)，All India Inst Med Sci, Dr RP Ctr Ophthalm Sci, Retina & Uvea Serv, New Delhi 110029, India.
EM venkyprao@yahoo.com
OI Takkar, Brijesh/0000-0001-5779-7645
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NR 17
TC 4
Z9 4
U1 0
U2 2
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
   LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0306-9877
EI 1532-2777
J9 MED HYPOTHESES
JI Med. Hypotheses
PD APR
PY 2018
VL 113
BP 72
EP 73
DI 10.1016/j.mehy.2018.02.024
PG 2
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA GC4MU
UT WOS:000429759400017
PM 29523299
DA 2022-11-30
ER

PT J
AU Fabrizio, C
   Termine, A
   Caputo, V
   Megalizzi, D
   Zampatti, S
   Falsini, B
   Cusumano, A
   Eandi, CM
   Ricci, F
   Giardina, E
   Strafella, C
   Cascella, R
AF Fabrizio, Carlo
   Termine, Andrea
   Caputo, Valerio
   Megalizzi, Domenica
   Zampatti, Stefania
   Falsini, Benedetto
   Cusumano, Andrea
   Eandi, Chiara Maria
   Ricci, Federico
   Giardina, Emiliano
   Strafella, Claudia
   Cascella, Raffaella
TI WARE: Wet AMD Risk-Evaluation Tool as a Clinical Decision-Support System
   Integrating Genetic and Non-Genetic Factors
SO JOURNAL OF PERSONALIZED MEDICINE
LA English
DT Article
DE AMD; aging; tool; risk evaluation; genetic and non-genetic factors;
   personalized approach
ID MACULAR DEGENERATION; PROGRESSION
AB Given the multifactorial features characterizing age-related macular degeneration (AMD), the availability of a tool able to provide the individual risk profile is extremely helpful for personalizing the follow-up and treatment protocols of patients. To this purpose, we developed an open-source computational tool named WARE (Wet AMD Risk Evaluation), able to assess the individual risk profile for wet AMD based on genetic and non-genetic factors. In particular, the tool uses genetic risk measures normalized for their relative frequencies in the general population and disease prevalence. WARE is characterized by a user-friendly web page interface that is intended to assist clinicians in reporting risk assessment upon patient evaluation. When using the tool, plots of population risk distribution highlight a "low-risk zone" and a "high-risk zone" into which subjects can fall depending on their risk-assessment result. WARE represents a reliable population-specific computational system for wet AMD risk evaluation that can be exploited to promote preventive actions and personalized medicine approach for affected patients or at-risk individuals. This tool can be suitable to compute the disease risk adjusted to different populations considering their specific genetic factors and related frequencies, non-genetic factors, and the disease prevalence.
C1 [Fabrizio, Carlo; Termine, Andrea] IRCCS Santa Lucia Fdn, Data Sci Unit, CERC, I-00143 Rome, Italy.
   [Caputo, Valerio; Megalizzi, Domenica; Zampatti, Stefania; Giardina, Emiliano; Strafella, Claudia] IRCCS Santa Lucia Fdn, Genom Med Lab UILDM, I-00179 Rome, Italy.
   [Falsini, Benedetto] Fdn Policlin Univ A Gemelli IRCCS, Ophthalmol Unit, I-00168 Rome, Italy.
   [Cusumano, Andrea] Univ Roma Tor Vergata, Dept Expt Med, Via Montpellier, I-00133 Rome, Italy.
   [Eandi, Chiara Maria] Univ Torino, Dept Surg Sci, I-10124 Turin, Italy.
   [Ricci, Federico] Univ Roma Tor Vergata, PTV Fdn, UOSD Retinal Dis, I-00133 Rome, Italy.
   [Giardina, Emiliano; Cascella, Raffaella] Univ Roma Tor Vergata, Dept Biomed & Prevent, I-00133 Rome, Italy.
   [Cascella, Raffaella] Catholic Univ Our Lady Good Counsel, Dept Biomed Sci, Tirana 1000, Albania.
C3 IRCCS Santa Lucia; IRCCS Santa Lucia; Catholic University of the Sacred
   Heart; IRCCS Policlinico Gemelli; University of Rome Tor Vergata;
   University of Turin; University of Rome Tor Vergata; University of Rome
   Tor Vergata
RP Giardina, E (通讯作者)，IRCCS Santa Lucia Fdn, Genom Med Lab UILDM, I-00179 Rome, Italy.; Giardina, E (通讯作者)，Univ Roma Tor Vergata, Dept Biomed & Prevent, I-00133 Rome, Italy.
EM c.fabrizio@hsantalucia.it; a.termine@hsantalucia.it;
   v.caputo91@gmail.com; domenica.megalizzi96@gmail.com;
   stefania.zampatti@gmail.com; benedetto.falsini@unicatt.it;
   cusumano@cusumano.com; chiara.eandi@unito.it; rccfrc00@gmail.com;
   emiliano.giardina@uniroma2.it; claudia.strafella@gmail.com;
   raffaella.cascella@uniroma2.it
RI Fabrizio, Carlo/GYA-1274-2022
OI Fabrizio, Carlo/0000-0002-7824-8423; Termine,
   Andrea/0000-0003-4374-7430; Falsini, Benedetto/0000-0002-1694-1062;
   Strafella, Claudia/0000-0003-1334-0920; Caputo,
   Valerio/0000-0002-3503-3318; Megalizzi, Domenica/0000-0001-9517-0165
CR 1000 Genomes Project Consortium, 2015, Nature, V526, P68, DOI 10.1038/nature15393
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NR 22
TC 0
Z9 0
U1 2
U2 2
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2075-4426
J9 J PERS MED
JI J. Pers. Med.
PD JUL
PY 2022
VL 12
IS 7
AR 1034
DI 10.3390/jpm12071034
PG 9
WC Health Care Sciences & Services; Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Health Care Sciences & Services; General & Internal Medicine
GA 3J2UE
UT WOS:000833254700001
PM 35887531
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Pin, K
   Chang, JH
   Nam, Y
AF Pin, Kuntha
   Chang, Jee Ho
   Nam, Yunyoung
TI Comparative Study of Transfer Learning Models for Retinal Disease
   Diagnosis from Fundus Images
SO CMC-COMPUTERS MATERIALS & CONTINUA
LA English
DT Article
DE Multiclass classification; deep neural networks; glaucoma; age-related
   macular degeneration; diabetic retinopathy; transfer learning; qual-ity
   evaluation
ID CONVOLUTIONAL NEURAL-NETWORKS; DIABETIC-RETINOPATHY; DEEP;
   CLASSIFICATION
AB While the usage of digital ocular fundus image has been widespread in ophthalmology practice, the interpretation of the image has been still on the hands of the ophthalmologists which are quite costly. We explored a robust deep learning system that detects three major ocular diseases: diabetic retinopathy (DR), glaucoma (GLC), and age-related macular degeneration (AMD). The proposed method is composed of two steps. First, an initial quality evaluation in the classification system is proposed to filter out poorquality images to enhance its performance, a technique that has not been explored previously. Second, the transfer learning technique is used with various convolutional neural networks (CNN) models that automatically learn a thousand features in the digital retinal image, and are based on those features for diagnosing eye diseases. Comparison performance of many models is conducted to find the optimal model which fits with fundus classification. Among the different CNN models, DenseNet-201 outperforms others with an area under the receiver operating characteristic curve of 0.99. Furthermore, the corresponding specificities for healthy, DR, GLC, and AMD patients are found to be 89.52%, 96.69%, 89.58%, and 100%, respectively. These results demonstrate that the proposed method can reduce the time-consumption by automatically diagnosing multiple eye diseases using computer-aided assistance tools.
C1 [Pin, Kuntha] Soonchunhyang Univ, Dept ICT Convergence, Asan 31538, South Korea.
   [Chang, Jee Ho] Soonchunhyang Univ, Coll Med, Bucheon Hosp, Dept Ophthalmol, Bucheon 420767, South Korea.
   [Nam, Yunyoung] Soonchunhyang Univ, Dept Comp Sci & Engn, Asan 31538, South Korea.
C3 Soonchunhyang University; Soonchunhyang University; Soonchunhyang
   University
RP Nam, Y (通讯作者)，Soonchunhyang Univ, Dept Comp Sci & Engn, Asan 31538, South Korea.
EM ynam@sch.ac.kr
FU National Research Foundation of Korea (NRF) - Korea government (MSIT)
   [NRF-2021R1A2C1010362]; Soonchunhyang University Research Fund
FX Funding Statement: This work was supported by the National Research
   Foundation of Korea (NRF) grant funded by the Korea government (MSIT)
   (No. NRF-2021R1A2C1010362) and the Soonchunhyang University Research
   Fund.
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NR 37
TC 1
Z9 1
U1 1
U2 8
PU TECH SCIENCE PRESS
PI HENDERSON
PA 871 CORONADO CENTER DR, SUTE 200, HENDERSON, NV 89052 USA
SN 1546-2218
EI 1546-2226
J9 CMC-COMPUT MATER CON
JI CMC-Comput. Mat. Contin.
PY 2022
VL 70
IS 3
BP 5821
EP 5834
DI 10.32604/cmc.2022.021943
PG 14
WC Computer Science, Information Systems; Materials Science,
   Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Computer Science; Materials Science
GA WH0FI
UT WOS:000707364500011
OA gold
DA 2022-11-30
ER

PT J
AU Liisborg, C
   Skov, V
   Kjaer, L
   Hasselbalch, HC
   Sorensen, TL
AF Liisborg, Charlotte
   Skov, Vibe
   Kjaer, Lasse
   Hasselbalch, Hans Carl
   Sorensen, Torben Lykke
TI Retinal drusen in patients with chronic myeloproliferative blood cancers
   are associated with an increased proportion of senescent T cells and
   signs of an aging immune system
SO AGING-US
LA English
DT Article
DE age-related macular degeneration; drusen; myeloproliferative neoplasms;
   chronic low-grade inflammation; immunosenescence; T cells
ID MACULAR DEGENERATION; EYE DISEASE; NAIVE; MAINTENANCE; MICE
AB The cause of age-related macular degeneration (AMD) is unknown, but evidence indicates that both innate and adaptive immunity play a role in the pathogenesis. Our recent work has investigated AMD in patients with myeloproliferative neoplasms (MPNs) since they have increased drusen and AMD prevalence. We have previously found increased levels of chronic low-grade inflammation (CLI) in MPN patients with drusen (MPNd) compared to MPN patients with normal retinas (MPNn). CLI and AMD are both associated with aging, and we, therefore, wanted to study immunosenescence markers in MPNd, MPNn, and AMD. The purpose was to identify differences between MPNd and MPNn, which might reveal novel information relevant to drusen pathophysiology and thereby the AMD pathogenesis. Our results suggest that MPNd have a T cell differentiation profile resembling AMD and more effector memory T cells than MPNn. The senescence associated-secretory-phenotype (SASP) is associated with effector T cells. SASP is thought to play a role in driving CLI seen with advancing age. Senescent cells with SASP may damage healthy tissue, including the eye tissues affected in AMD. The finding of increased effector cells in MPNd could implicate a role for adaptive immunity and senescent T cells together with increased CLI in drusen pathophysiology.
C1 [Liisborg, Charlotte; Sorensen, Torben Lykke] Zealand Univ Hosp, Dept Ophthalmol, DK-4000 Roskilde, Denmark.
   [Liisborg, Charlotte; Hasselbalch, Hans Carl; Sorensen, Torben Lykke] Univ Copenhagen, Fac Hlth & Med Sci, DK-2200 Copenhagen, Denmark.
   [Skov, Vibe; Kjaer, Lasse; Hasselbalch, Hans Carl] Zealand Univ Hosp, Dept Hematol, DK-4000 Roskilde, Denmark.
C3 University of Copenhagen
RP Liisborg, C (通讯作者)，Zealand Univ Hosp, Dept Ophthalmol, DK-4000 Roskilde, Denmark.; Liisborg, C (通讯作者)，Univ Copenhagen, Fac Hlth & Med Sci, DK-2200 Copenhagen, Denmark.
EM liisborg@c.dk
OI Liisborg, Charlotte/0000-0002-6353-6027
FU Fight for Sight, Denmark; Region Zealand's research promotion fund
FX The corresponding author's Ph.D., including this work, was funded by
   Fight for Sight, Denmark, and Region Zealand's research promotion fund.
   The sponsors are public and non-profit organizations. They had no role
   in the study's design and conduct; collection, analysis, and
   interpretation of the data; preparation, review, or approval of the
   manuscript; or the decision to submit the manuscript for publication.
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NR 61
TC 1
Z9 1
U1 1
U2 1
PU IMPACT JOURNALS LLC
PI ORCHARD PARK
PA 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD DEC 31
PY 2021
VL 13
IS 24
BP 25763
EP 25777
PG 15
WC Cell Biology; Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Geriatrics & Gerontology
GA YC9SQ
UT WOS:000740024100010
PM 34954692
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Xu, JX
   Liu, XL
   Zhang, XY
   Marshall, B
   Dong, Z
   Smith, SB
   Espinosa-Heidmann, DG
   Zhang, M
AF Xu, Jinxian
   Liu, Xinglou
   Zhang, Xinyan
   Marshall, Brendan
   Dong, Zheng
   Smith, Sylvia B.
   Espinosa-Heidmann, Diego G.
   Zhang, Ming
TI Retinal and Choroidal Pathologies in Aged BALB/c Mice Following Systemic
   Neonatal Murine Cytomegalovirus Infection
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; PROMOTES ANGIOGENESIS; CELL-DEATH; APOPTOSIS;
   REACTIVATION; EXPRESSION; PROTEIN; VIRUS; MCMV; RETINITIS
AB Although pathologies associated with acute virus infections have been extensively studied, the effects of long-term latent virus infections are less well understood. Human cytomegalovirus, which infects 50% to 80% of humans, is usually acquired during early life and persists in a latent state for the lifetime. The purpose of this study was to determine whether systemic murine cytomegalovirus (MCMV) infection acquired early in life disseminates to and becomes latent in the eye and if ocular MCMV can trigger in situ inflammation and occurrence of ocular pathology. This study found that neonatal infection of BALB/c mice with MCMV resulted in dissemination of virus to the eye, where it localized principally to choroidal endothelia and pericytes and less frequently to the retinal pigment epithelium (RPE) cells. MCMV underwent ocular latency, which was associated with expression of multiple virus genes and from which MCMV could be reactivated by immunosuppression. Latent ocular infection was associated with significant up-regulation of several inflammatory/angiogenic factors. Retinal and choroidal pathologies developed in a progressive manner, with deposits appearing at both basal and apical aspects of the RPE, RPE/choroidal atrophy, photoreceptor degeneration, and neovascularization. The pathologies induced by long-term ocular MCMV latency share features of previously described human ocular diseases, such as age-related macular degeneration.
C1 [Xu, Jinxian; Liu, Xinglou; Zhang, Xinyan; Marshall, Brendan; Dong, Zheng; Smith, Sylvia B.; Zhang, Ming] Augusta Univ, Dept Anat & Cell Biol, Augusta, GA USA.
   [Smith, Sylvia B.; Espinosa-Heidmann, Diego G.] Augusta Univ, Dept Ophthalmol, Augusta, GA USA.
   [Xu, Jinxian; Liu, Xinglou; Zhang, Xinyan; Smith, Sylvia B.; Espinosa-Heidmann, Diego G.; Zhang, Ming] Augusta Univ, James & Jean Vision Discovery Inst, Augusta, GA USA.
   [Dong, Zheng] Augusta Univ, Med Coll Georgia, Augusta, GA USA.
   [Dong, Zheng] Charlie Norwood Vet Affairs Med Ctr, Augusta, GA USA.
C3 University System of Georgia; Augusta University; University System of
   Georgia; Augusta University; University System of Georgia; Augusta
   University; University System of Georgia; Augusta University; US
   Department of Veterans Affairs; Veterans Health Administration (VHA)
RP Zhang, M (通讯作者)，Augusta Univ, Med Coll Georgia, Dept Cellular Biol & Anat, Room CB2815, Augusta, GA 30912 USA.
EM mzhang@augusta.edu
OI Zhang, Ming/0000-0002-4012-3932; Xu, Jinxian/0000-0001-9674-8029
FU NIH [RO1 EY026642, P30 EY031631]; BrightFocus Foundation
FX Supported by NIH grants RO1 EY026642 (M.Z.) and P30 EY031631 (S.B.S.)
   and a BrightFocus Foundation grant (M.S).
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NR 100
TC 0
Z9 0
U1 0
U2 7
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 2021
VL 191
IS 10
BP 1787
EP 1804
DI 10.1016/j.ajpath.2021.06.008
EA SEP 2021
PG 18
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA UY9ON
UT WOS:000701844500014
PM 34197777
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Pariente, A
   Perez-Sala, A
   Ochoa, R
   Pelaez, R
   Larrayoz, IM
AF Pariente, Ana
   Perez-Sala, Alvaro
   Ochoa, Rodrigo
   Pelaez, Rafael
   Larrayoz, Ignacio M.
TI Genome-Wide Transcriptomic Analysis Identifies Pathways Regulated by
   Sterculic Acid in Retinal Pigmented Epithelium Cells
SO CELLS
LA English
DT Article
DE sterculic acid; cell death; macular degeneration; genetic response
ID STEAROYL-COA DESATURASE; CONJUGATED LINOLEIC-ACID; AMYLOID-BETA;
   INHIBITION; OXYSTEROLS; INFLAMMATION; CIS-9; INVOLVEMENT; LIPOGENESIS;
   MECHANISMS
AB In addition to its predominant role in lipid metabolism and body weight control, SCD1 has emerged recently as a potential new target for the treatment of various diseases. Sterculic acid (SA) is a cyclopropene fatty acid with numerous biological activities, generally attributed to its Stearoyl-CoA desaturase (SCD) inhibitory properties. Additional effects exerted by SA, independently of SCD inhibition, may be mediating anti-inflammatory and protective roles in retinal diseases such as age-related macular degeneration (AMD), but the mechanisms involved are poorly understood. In order to provide insights into those mechanisms, genome-wide transcriptomic analyses were carried out in mRPE cells exposed to SA for 24 h. Integrative functional enrichment analysis of genome-wide expression data provided biological insight about the protective mechanisms induced by SA. On the one hand, pivotal genes related to fatty acid biosynthesis, steroid biosynthesis, cell death, actin-cytoskeleton reorganization and extracellular matrix-receptor interaction were significantly downregulated by exposition to SA. On the other hand, genes related to fatty acid degradation and beta-oxidation were significantly upregulated. In conclusion, SA administration to RPE cells regulates crucial pathways related to cell proliferation, inflammation and cell death that may be of interest for the treatment of ocular diseases.
C1 [Pariente, Ana; Perez-Sala, Alvaro; Ochoa, Rodrigo; Pelaez, Rafael; Larrayoz, Ignacio M.] Ctr Biomed Res La Rioja CIBIR, Neurodegenerat Area, Biomarkers & Mol Signaling Grp, Piqueras 98, Logrono 26006, Spain.
RP Larrayoz, IM (通讯作者)，Ctr Biomed Res La Rioja CIBIR, Neurodegenerat Area, Biomarkers & Mol Signaling Grp, Piqueras 98, Logrono 26006, Spain.
EM apariente@riojasalud.es; aperez@riojasalud.es; rochoaf@riojasalud.es;
   rpelaez@riojasalud.es; ilarrayoz@riojasalud.es
RI Larrayoz, Ignacio M/I-5613-2012
OI Larrayoz, Ignacio M/0000-0003-1629-152X; Pariente Delgado,
   Ana/0000-0001-9046-6629; Pelaez, Rafael/0000-0002-4047-6017; Perez Sala,
   Alvaro/0000-0002-7310-6792
FU Fundacion Rioja Salud; Instituto de Salud Carlos III-FEDER (Fondo
   Europeo de Desarrollo Regional, a way to build Europe); Miguel Servet
   contract [CP15/00198]
FX This research was funded by the Fundacion Rioja Salud and the Instituto
   de Salud Carlos III-FEDER (Fondo Europeo de Desarrollo Regional, a way
   to build Europe). I.M.L. is supported by a Miguel Servet contract
   (CP15/00198).
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NR 63
TC 6
Z9 6
U1 2
U2 4
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2073-4409
J9 CELLS-BASEL
JI Cells
PD MAY
PY 2020
VL 9
IS 5
DI 10.3390/cells9051187
PG 18
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA LW7RF
UT WOS:000539340200121
PM 32403229
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Wong, W
AF Wong, Winston
TI Managed Care Opportunities and Approaches to Select Treatment for Sight
   Preservation
SO AMERICAN JOURNAL OF MANAGED CARE
LA English
DT Article
ID MACULAR DEGENERATION; RANIBIZUMAB; THERAPY; COSTS
AB Neovascular (or wet) age-related macular degeneration (AMD) affects more than 10% of people older than 65 years in North America, Europe, Australia, and Asia. It is estimated that about 11 million Americans have some form of AMD, with that number expected to double by 2050. Approximately 20% of patients will advance from a nonneovascular form of the disease to neovascular AMD, which is associated with central visual acuity loss that can result in severe visual impairment and blindness. Improvements in vision preservation and quality of life require regular clinical visits for intravitreal therapy, which, while effective, come at high cost and potential financial strain, often complicated by the fact that most patients with the disease will be covered by Medicare and subject to the regulations and restrictions within their insurance plans. The requirement for frequent treatment also threatens adherence to therapy, and many patients do not follow up clinically as advised. The confluence of high-cost drug therapy and growing demand for treatment of a sight-threatening disease creates a mandate that managed care professionals and payers focus on current and emerging management options in neovascular AMD and on how to administer therapies in both a clinically responsible and cost-effective manner to diminish risk of vision loss and improve overall patient outcomes.
C1 [Wong, Winston] W Squared Grp, Longboat Key, FL 34228 USA.
RP Wong, W (通讯作者)，W Squared Grp, Longboat Key, FL 34228 USA.
EM wwong@wsquaredgroup.com
FU Genentech
FX This activity is supported by an educational grant from Genentech.
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   Schmier JK, 2012, AM J OPHTHALMOL, V154, P675, DOI 10.1016/j.ajo.2012.04.017
   Sharma A, 2018, CLIN OPHTHALMOL, V12, P2137, DOI 10.2147/OPTH.S180393
   Singh RP, 2018, GLOBAL TRENDS RETINA
   Stone TW, 2019, ASRS 2019 PREFERENCE
   Williams GA, REV OPHTHALMOLOGY
   Yang SQ, 2016, DRUG DES DEV THER, V10, P1857, DOI 10.2147/DDDT.S97653
NR 36
TC 1
Z9 1
U1 0
U2 1
PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC
PI PLAINSBORO
PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA
SN 1088-0224
J9 AM J MANAG CARE
JI Am. J. Manag. Care
PD MAY
PY 2020
VL 26
IS 5
SU S
BP S112
EP S117
PG 6
WC Health Care Sciences & Services; Health Policy & Services; Medicine,
   General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Health Care Sciences & Services; General & Internal Medicine
GA PW7VJ
UT WOS:000610877700002
PM 32479027
DA 2022-11-30
ER

PT J
AU Wang, HB
   Kunz, E
   Stoddard, GJ
   Hauswirth, WW
   Hartnett, MEL
AF Wang, Haibo
   Kunz, Eric
   Stoddard, Gregory J.
   Hauswirth, William W.
   Hartnett, M. E. Lizabeth
TI Optimal Inhibition of Choroidal Neovascularization by scAAV2 with VMD2
   Promoter-driven Active Rap1a in the RPE
SO SCIENTIFIC REPORTS
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; VEGF; EXPRESSION; AAV;
   INFLAMMATION; ACTIVATION; DISEASE
AB Age-related macular degeneration (AMD) is a multifactorial chronic disease that requires long term treatment. Gene therapy is being considered as a promising tool to treat AMD. We found that increased activation of Rap1a in the retinal pigment epithelium (RPE) reduces oxidative signaling to maintain barrier integrity of the RPE and resist neural sensory retinal angiogenesis from choroidal endothelial cell invasion. To optimally deliver constitutively active Rap1a (CARap1a) into the RPE of wild type mice, self-complementary AAV2 (scAAV2) vectors driven by two different promoters, RPE65 or VMD2, were generated and tested for optimal active Rap1a expression and inhibition of choroidal neovascularization (CNV) induced by laser injury. scAAV2-VMD2, but not scAAV2-RPE65, specifically and efficiently transduced the RPE to increase active Rap1a protein in the RPE. Mice with increased Rap1a from the scAAV2-VMD2-CARap1a had a significant reduction in CNV compared to controls. Increased active Rap1a in the RPE in vivo or in vitro inhibited inflammatory and angiogenic signaling determined by decreased activation of NF-kappa B and expression of VEGF without causing increased cell death or autophagy measured by increased LCA3/B. Our study provides a potential future strategy to deliver active Rap1a to the RPE in order to protect against both atrophic and neovascular AMD.
C1 [Wang, Haibo; Kunz, Eric; Hartnett, M. E. Lizabeth] John A Moran Eye Ctr, Salt Lake City, UT 84132 USA.
   [Stoddard, Gregory J.] Univ Utah, Dept Internal Med, Salt Lake City, UT 84132 USA.
   [Hauswirth, William W.] Univ Florida, Coll Med, Dept Ophthalmol, Gainesville, FL 32610 USA.
C3 Utah System of Higher Education; University of Utah; State University
   System of Florida; University of Florida
RP Hartnett, MEL (通讯作者)，John A Moran Eye Ctr, Salt Lake City, UT 84132 USA.
EM ME.Hartnett@hsc.utah.edu
RI Core, Vector/CAF-4832-2022
FU National Institutes of Health [EY014800, R01EY015130, R01EY017011];
   Research to Prevent Blindness, Inc., New York, NY; NATIONAL EYE
   INSTITUTE [R01EY017011] Funding Source: NIH RePORTER
FX This work was supported by the National Institutes of Health EY014800
   (Core Funding), R01EY015130 and R01EY017011 to M.E.H. and an
   Unrestricted Grant from Research to Prevent Blindness, Inc., New York,
   NY, to the Department of Ophthalmology & Visual Sciences, University of
   Utah and to the Department of Ophthalmology, University of Florida. We
   thank Dr. R Jude Samulski and Dr. T. Michael Redmond for helping us with
   sc-AAV2-RPE65 viral constructs.
CR Ablonczy Z, 2014, FASEB J, V28, P2369, DOI 10.1096/fj.13-248021
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NR 34
TC 4
Z9 5
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD OCT 31
PY 2019
VL 9
AR 15732
DI 10.1038/s41598-019-52163-z
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA JI4LW
UT WOS:000493439600030
PM 31673119
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Muraleva, NA
   Kozhevnikova, OS
   Fursova, AZ
   Kolosova, NG
AF Muraleva, Natalia A.
   Kozhevnikova, Oyuna S.
   Fursova, Anzhela Z.
   Kolosova, Nataliya G.
TI Suppression of AMD-Like Pathology by Mitochondria-Targeted Antioxidant
   SkQ1 Is Associated with a Decrease in the Accumulation of Amyloid beta
   and in mTOR Activity
SO ANTIOXIDANTS
LA English
DT Article
DE age-related macular degeneration; mitochondria-targeted antioxidant
   SkQ1; amyloid beta; mTOR; OXYS rats
ID ACCELERATED OXYS RATS; ALZHEIMERS-DISEASE; AGE; SENESCENCE; RETINOPATHY;
   DEGENERATION; AUTOPHAGY; EYE; EXPRESSION; PATHWAY
AB Age-related macular degeneration (AMD) is a major cause of irreversible visual impairment and blindness in developed countries, and the molecular pathogenesis of AMD is poorly understood. Recent studies strongly indicate that amyloid beta (A beta) accumulation -found in the brain and a defining feature of Alzheimer's disease-also forms in the retina in both Alzheimer's disease and AMD. The reason why highly neurotoxic proteins of consistently aggregate in the aging retina, and to what extent they contribute to AMD, remains to be fully addressed. Nonetheless, the hypothesis that A beta is a therapeutic target in AMD is debated. Here, we showed that long-term treatment with SkQ1 (250 nmol/[kg body weight] daily from the age of 1.5 to 22 months) suppressed the development of AMD-like pathology in senescence-accelerated OXYS rats by reducing the level of A beta and suppressing the activity of mTOR in the retina. Inhibition of mTOR signaling activity, which plays key roles in aging and age-related diseases, can be considered a new mechanism of the prophylactic effect of SkQ1. It seems probable that dietary supplementation with mitochondria-targeted antioxidant SkQ1 can be a good prevention strategy to maintain eye health and possibly a treatment of AMD.
C1 [Muraleva, Natalia A.; Kozhevnikova, Oyuna S.; Fursova, Anzhela Z.; Kolosova, Nataliya G.] Inst Cytol & Genet SB RAS, Pr Lavrentyeva 10, Novosibirsk 630090, Russia.
   [Kolosova, Nataliya G.] NN Vorozhtsov Novosibirsk Inst Organ Chem SB RAS, 9 Lavrentieva Ave, Novosibirsk 630090, Russia.
C3 Russian Academy of Sciences; Institute of Cytology & Genetics ICG SB
   RAS; Russian Academy of Sciences; Vorozhtsov Novosibirsk Institute of
   Organic Chemistry
RP Kolosova, NG (通讯作者)，Inst Cytol & Genet SB RAS, Pr Lavrentyeva 10, Novosibirsk 630090, Russia.; Kolosova, NG (通讯作者)，NN Vorozhtsov Novosibirsk Inst Organ Chem SB RAS, 9 Lavrentieva Ave, Novosibirsk 630090, Russia.
EM Myraleva@bionet.nsc.ru; oidopova@bionet.nsc.ru;
   anzhellafursova@yandex.ru; Kolosova@bionet.nsc.ru
RI Kolosova, Nataliya G/AAR-7409-2020; fursova, anzhella/AAE-1495-2022;
   Muraleva, Natalia/S-2392-2018; Kozhevnikova, Oyuna S./H-3588-2016
OI Kolosova, Nataliya G/0000-0003-2398-8544; fursova,
   anzhella/0000-0001-6311-5452; Muraleva, Natalia/0000-0002-0665-1723;
   Kozhevnikova, Oyuna S./0000-0001-6475-4061
FU Russian Foundation for Basic Research [18-315-00216]; Russian Ministry
   of Science and Education [14.W03.31.0034]
FX This work was supported by the Russian Foundation for Basic Research
   [grant number 18-315-00216] and by the Russian Ministry of Science and
   Education within Grant 14.W03.31.0034 (megagrant).
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NR 64
TC 12
Z9 15
U1 0
U2 1
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2076-3921
J9 ANTIOXIDANTS-BASEL
JI Antioxidants
PD JUN
PY 2019
VL 8
IS 6
DI 10.3390/antiox8060177
PG 13
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Food Science &
   Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Food Science
   & Technology
GA II6FJ
UT WOS:000475288200029
PM 31208023
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Wu, MJ
   Liu, YM
   Zhang, H
   Lian, ML
   Chen, J
   Jiang, HY
   Xu, Y
   Shan, G
   Wu, SZ
AF Wu, Mengjuan
   Liu, Yimei
   Zhang, He
   Lian, Meiling
   Chen, Juan
   Jiang, Haiyan
   Xu, Ying
   Shan, Ge
   Wu, Shengzhou
TI Intravenous injection of l-aspartic acid beta-hydroxamate attenuates
   choroidal neovascularization via anti-VEGF and anti-inflammation
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Retinal pigment epithelial cell;
   Macrophage chemotactic protein 1; VEGF; l-Aspartic acid
   beta-hydroxamate; Phenazine methosulfate; Transwell migration
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL-PIGMENT EPITHELIUM;
   ANGIOTENSIN-CONVERTING ENZYME; OF-FUNCTION MUTATION; SERINE RACEMASE;
   MACULAR DEGENERATION; INTRAVITREAL INJECTION; SOLUBLE VEGF;
   NITRIC-OXIDE; MOUSE MODEL
AB Choroidal neovascularization (CNV) is a hallmark of exudative age-related macular degeneration (exAMD) and a major cause of visual loss in AMD. Despite the widespread use of anti-VEGF therapy, serious adverse effects arise from repeated intravitreal injection of anti-VEGF antibodies, which warrant alternative strategy. We report herein that in a CNV murine model created by krypton red laser, intravenous injection of a serine racemase inhibitor, l-Aspartic acid beta-hydroxamate (L-ABH), significantly reduced CNV at the dose 6 mg/kg on the first day before and followed by 3 mg/kg on the third day after laser injury. The CNV volumes were analyzed with isolectin GS-IB4 staining on choroidal/RPE flat mounts on the seventh day after laser injury. Injection of L-ABH did not produce negative effects on retinal function and visual behavior. To dissect the mechanism in vitro, pretreatment with L-ABH in primary RPE cultures significantly reduced production of vascular endothelial growth factor (VEGF) and macrophage chemotactic protein 1 (MCP-1) by TNF alpha-primed RPEs. Consistent with these observations, L-ABH pretreatment significantly attenuated macrophage migration mediated by TNF alpha-primed RPE. Collectively, intravenous injection of L-ABH significantly reduced CNV volumes via reducing production of VEGF and MCP-1 by inflammation-primed RPEs.
C1 [Wu, Mengjuan; Liu, Yimei; Zhang, He; Lian, Meiling; Chen, Juan; Jiang, Haiyan; Wu, Shengzhou] Wenzhou Med Univ, Sch Optometry & Ophthalmol, Wenzhou 325027, Peoples R China.
   [Wu, Mengjuan; Liu, Yimei; Zhang, He; Lian, Meiling; Chen, Juan; Jiang, Haiyan; Wu, Shengzhou] Wenzhou Med Univ, Eye Hosp, Wenzhou 325027, Peoples R China.
   [Wu, Mengjuan; Liu, Yimei; Zhang, He; Lian, Meiling; Chen, Juan; Jiang, Haiyan; Wu, Shengzhou] State Key Lab Optometry Ophthalmol & Visual Sci, Wenzhou 325027, Zhejiang, Peoples R China.
   [Xu, Ying] Jinan Univ, Guangdong Hongkong Macau Inst CNS Regenerat, Guangzhou 510632, Guangdong, Peoples R China.
   [Shan, Ge] Univ Sci & Technol China, Sch Life Sci, CAS Ctr Excellence Mol Cell Sci, CAS Key Lab Innate Immun & Chron Dis, Hefei 230027, Anhui, Peoples R China.
C3 Wenzhou Medical University; Wenzhou Medical University; Jinan
   University; Chinese Academy of Sciences; University of Science &
   Technology of China, CAS
RP Wu, SZ (通讯作者)，Wenzhou Med Univ, Sch Optometry & Ophthalmol, Wenzhou 325027, Peoples R China.; Wu, SZ (通讯作者)，Wenzhou Med Univ, Eye Hosp, Wenzhou 325027, Peoples R China.
EM wszlab@wmu.edu.cn
RI wu, shengzhou/ABG-8579-2021; Shan, Ge/B-7323-2016
OI wu, shengzhou/0000-0003-1154-2369; Jiang, Haiyan/0000-0003-2756-4335;
   Wu, Mengjuan/0000-0002-9558-2159; Shan, Ge/0000-0002-3561-2088; Xu,
   Ying/0000-0002-9987-2057
FU State Key Laboratory of Ophthalmology, Optometry and Visual Science,
   Wenzhou Medical University [K171202]; Zhejiang Provincial Natural
   Science Foundation, China [LY18H120003]
FX This study was supported by the Project of State Key Laboratory of
   Ophthalmology, Optometry and Visual Science, Wenzhou Medical University
   (K171202); Zhejiang Provincial Natural Science Foundation, China
   (LY18H120003). The authors have found no conflict of interests to
   disclose.
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NR 45
TC 4
Z9 5
U1 2
U2 11
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD MAY
PY 2019
VL 182
BP 93
EP 100
DI 10.1016/j.exer.2019.03.018
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HY6RV
UT WOS:000468258300011
PM 30917905
DA 2022-11-30
ER

PT J
AU Anand-Apte, B
   Chao, JR
   Singh, R
   Stohr, H
AF Anand-Apte, Bela
   Chao, Jennifer R.
   Singh, Ruchira
   Stoehr, Heidi
TI Sorsby fundus dystrophy: Insights from the past and looking to the
   future
SO JOURNAL OF NEUROSCIENCE RESEARCH
LA English
DT Review
ID GENOME-WIDE ASSOCIATION; N-TERMINAL DOMAIN; TISSUE INHIBITOR;
   METALLOPROTEINASES-3 TIMP3; CHOROIDAL NEOVASCULARIZATION; RETICULAR
   PSEUDODRUSEN; MACULAR DEGENERATION; CELL LINES; MUTATION; GENE
AB Sorsby fundus dystrophy (SFD), an autosomal dominant, fully penetrant, degenerative disease of the macula, is manifested by symptoms of night blindness or sudden loss of visual acuity, usually in the third to fourth decades of life due to choroidal neovascularization (CNV). SFD is caused by specific mutations in the Tissue Inhibitor of Metalloproteinase-3, (TIMP3) gene. The predominant histo-pathological feature in the eyes of patients with SFD are confluent 20-30 m thick, amorphous deposits found between the basement membrane of the retinal pigment epithelium (RPE) and the inner collagenous layer of Bruch's membrane. SFD is a rare disease but it has generated significant interest because it closely resembles the exudative or "wet" form of the more common age-related macular degeneration (AMD). In addition, in both SFD and AMD donor eyes, sub-retinal deposits have been shown to accumulate TIMP3 protein. Understanding the molecular functions of wild-type and mutant TIMP3 will provide significant insights into the patho-physiology of SFD and perhaps AMD. This review summarizes the current knowledge on TIMP3 and how mutations in TIMP3 cause SFD to provide insights into how we can study this disease going forward. Findings from these studies could have potential therapeutic implications for both SFD and AMD.
C1 [Anand-Apte, Bela] Cleveland Clin Fdn, Cole Eye Inst, Dept Ophthalm Res, 9500 Euclid Ave, Cleveland, OH 44195 USA.
   [Anand-Apte, Bela] Cleveland Clin, Lerner Coll Med, Lerner Res Inst, Dept Ophthalmol, Cleveland, OH 44106 USA.
   [Anand-Apte, Bela] Cleveland Clin, Lerner Coll Med, Lerner Res Inst, Dept Mol Med, Cleveland, OH 44106 USA.
   [Chao, Jennifer R.] Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA.
   [Singh, Ruchira] Univ Rochester, UR Stem Cell & Regenerat Med Inst, Visual Sci 3Ctr, Flaum Eye Inst & Biomed Genet,Dept Ophthalmol, Rochester, NY USA.
   [Stoehr, Heidi] Univ Regensburg, Inst Human Genet, Regensburg, Germany.
C3 Cleveland Clinic Foundation; Case Western Reserve University; Cleveland
   Clinic Foundation; Case Western Reserve University; Cleveland Clinic
   Foundation; University of Washington; University of Washington Seattle;
   University of Rochester; University of Regensburg
RP Anand-Apte, B (通讯作者)，Cleveland Clin Fdn, Cole Eye Inst, Dept Ophthalm Res, 9500 Euclid Ave, Cleveland, OH 44195 USA.; Anand-Apte, B (通讯作者)，Cleveland Clin, Lerner Coll Med, Lerner Res Inst, Dept Ophthalmol, Cleveland, OH 44106 USA.; Anand-Apte, B (通讯作者)，Cleveland Clin, Lerner Coll Med, Lerner Res Inst, Dept Mol Med, Cleveland, OH 44106 USA.
EM anandab@ccf.org
OI Chao, Jennifer/0000-0002-6859-5552; Anand-Apte, Bela/0000-0002-4845-9094
FU BrightFocus Foundation; Center for Scientific Review [P30EY001730,
   P30EY025585, RO1EY026030, RO1EY026181, RO1EY027083, RO1EY028167,
   T32EY024236]; Foundation Fighting Blindness; Research to Prevent
   Blindness; NATIONAL EYE INSTITUTE [R01EY026030, R01EY028167,
   R01EY027083, P30EY025585, R01EY026181] Funding Source: NIH RePORTER
FX BrightFocus Foundation, Grant/Award Number: MDR Grant; Center for
   Scientific Review, Grant/Award Number: P30EY001730, P30EY025585,
   RO1EY026030, RO1EY026181, RO1EY027083, RO1EY028167 and T32EY024236;
   Foundation Fighting Blindness, Grant/Award Number: Center Grant and
   Individual Investigator Award; Research to Prevent Blindness,
   Grant/Award Number: Career Development Award and Unrestricted Grant
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NR 90
TC 19
Z9 19
U1 0
U2 2
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0360-4012
EI 1097-4547
J9 J NEUROSCI RES
JI J. Neurosci. Res.
PD JAN
PY 2019
VL 97
IS 1
SI SI
BP 88
EP 97
DI 10.1002/jnr.24317
PG 10
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA HA5VA
UT WOS:000450346100009
PM 30129971
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Yao, XC
   Son, T
   Kim, TH
   Lu, YM
AF Yao, Xincheng
   Son, Taeyoon
   Kim, Tae-Hoon
   Lu, Yiming
TI Functional optical coherence tomography of retinal photoreceptors
SO EXPERIMENTAL BIOLOGY AND MEDICINE
LA English
DT Review
DE Optical coherence tomography; intrinsic optical signal; age-related
   macular degeneration; photoreceptors
ID RESPONSES; SIGNALS
AB Age-related macular degeneration (AMD) is the leading cause of severe vision loss and legal blindness. It is known that retinal photoreceptors are the primary target of AMD. Therefore, a reliable method for objective assessment of photoreceptor function is needed for early detection and reliable treatment evaluation of AMD and other eye diseases such as retinitis pigmentosa that are known to cause photoreceptor dysfunctions. Stimulus-evoked intrinsic optical signal (IOS) changes promise a unique opportunity for objective assessment of physiological function of retinal photoreceptor and inner neurons. Instead of a comprehensive review, this mini-review is to provide a brief summary of our recent in vitro and in vivo optical coherence tomography (OCT) studies of stimulus-evoked IOS changes in animal retinas. By providing excellent axial resolution to differentiate individual retinal layers, depth-resolved OCT revealed rapid IOS response at the photoreceptor outer segment. The fast photoreceptor-IOS occurred almost right away (similar to 2 ms) after the onset of retinal stimulation, differentiating itself from slow IOS changes correlated with inner neural and hemodynamic changes. Further development of the functional IOS instruments and retinal stimulation protocols may provide a feasible solution to pursue clinical application of functional IOS imaging for objective assessment of human photoreceptors.
C1 [Yao, Xincheng; Son, Taeyoon; Kim, Tae-Hoon; Lu, Yiming] Univ Illinois, Dept Bioengn, Chicago, IL 60607 USA.
   [Yao, Xincheng] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA.
C3 University of Illinois System; University of Illinois Chicago;
   University of Illinois Chicago Hospital; University of Illinois System;
   University of Illinois Chicago; University of Illinois Chicago Hospital
RP Yao, XC (通讯作者)，Univ Illinois, Dept Bioengn, Chicago, IL 60607 USA.; Yao, XC (通讯作者)，Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA.
EM xcy@uic.edu
RI LU, YIMING/AAC-9992-2020; Kim, Taehoon/AAS-5818-2020; Son,
   Taeyoon/Q-4816-2017; Yao, Xincheng/ABA-1526-2020
OI LU, YIMING/0000-0002-4895-1484; Kim, Tae-Hoon/0000-0002-4391-4860
FU NIH [R01 EY023522, R01 EY024628, P30 EY001792]; Richard and Loan Hill
   endowment; Research to Prevent Blindness; NATIONAL EYE INSTITUTE
   [P30EY001792, R01EY024628, R01EY023522] Funding Source: NIH RePORTER
FX This research was supported in part by NIH grants R01 EY023522, R01
   EY024628, P30 EY001792; by Richard and Loan Hill endowment; by
   unrestricted grant from Research to Prevent Blindness.
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NR 39
TC 18
Z9 18
U1 0
U2 3
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 DEC
PY 2018
VL 243
IS 17-18
BP 1256
EP 1264
DI 10.1177/1535370218816517
PG 9
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA HI8BV
UT WOS:000456681200002
PM 30482040
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Kamoshita, M
   Toda, E
   Osada, H
   Narimatsu, T
   Kobayashi, S
   Tsubota, K
   Ozawa, Y
AF Kamoshita, Mamoru
   Toda, Eriko
   Osada, Hideto
   Narimatsu, Toshio
   Kobayashi, Saori
   Tsubota, Kazuo
   Ozawa, Yoko
TI Lutein acts via multiple antioxidant pathways in the photo-stressed
   retina
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MACULAR DEGENERATION; PIGMENT EPITHELIUM; LIGHT; DAMAGE; BLUE;
   ACTIVATION; EXPRESSION; INDUCTION; RHODOPSIN; JUNCTIONS
AB Lutein slows the progression of age-related macular degeneration (AMD), a leading cause of blindness in ageing societies. However, the underlying mechanisms remain elusive. Here, we evaluated lutein's effects on light-induced AMD-related pathological events. Balb/c mice exposed to light (2000 lux, 3 h) showed tight junction disruption in the retinal pigment epithelium (RPE) at 12 h, as detected by zona occludens-1 immunostaining. Substantial disruption remained 48 h after light exposure in the vehicle-treated group; however, this was ameliorated in the mice treated with intraperitoneal lutein at 12 h, suggesting that lutein promoted tight junction repair. In the photo-stressed RPE and the neighbouring choroid tissue, lutein suppressed reactive oxygen species and increased superoxide dismutase (SOD) activity at 24 h, and produced sustained increases in sod1 and sod2 mRNA levels at 48 h. SOD activity was induced by lutein in an RPE cell line, ARPE19. We also found that lutein suppressed upregulation of macrophage-related markers, f4/80 and mcp-1, in the RPE-choroid tissue at 18 h. In ARPE19, lutein reduced mcp-1 mRNA levels. These findings indicated that lutein promoted tight junction repair and suppressed inflammation in photo-stressed mice, reducing local oxidative stress by direct scavenging and most likely by induction of endogenous antioxidant enzymes.
C1 [Kamoshita, Mamoru; Toda, Eriko; Osada, Hideto; Narimatsu, Toshio; Ozawa, Yoko] Keio Univ, Sch Med, Lab Retinal Cell Biol, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan.
   [Kamoshita, Mamoru; Narimatsu, Toshio; Tsubota, Kazuo; Ozawa, Yoko] Keio Univ, Sch Med, Dept Ophthalmol, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan.
   [Kobayashi, Saori] Wakasa Seikatsu Co Ltd, Shimogyo Ku, 134 Chudoujiminami Cho, Kyoto 6008813, Japan.
C3 Keio University; Keio University
RP Ozawa, Y (通讯作者)，Keio Univ, Sch Med, Lab Retinal Cell Biol, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan.; Ozawa, Y (通讯作者)，Keio Univ, Sch Med, Dept Ophthalmol, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan.
EM ozawa@a5.keio.jp
RI Ozawa, Yoko/AAH-9888-2020; Kobayashi, Saori/GXV-3835-2022
OI Osada, Hideto/0000-0001-9971-8992
FU Ministry of Agriculture, Forestry and Fisheries of Japan; Wakasa
   Seikatsu Co. Ltd.
FX We appreciate Professor Masato Yasui and the members of the Department
   of Pharmacology, Keio University School of Medicine, and all the members
   of the RCB lab for their kind assistance during this study. This work
   was supported by a grant-in-aid 'A Scheme to Revitalize Agriculture and
   Fisheries in Disaster Area through Deploying Highly Advanced Technology'
   from the Ministry of Agriculture, Forestry and Fisheries of Japan, and
   by financial support from Wakasa Seikatsu Co. Ltd. SK is an employee of
   Wakasa Seikatsu Co. Ltd. and KT and YO received the grants shown above.
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NR 45
TC 64
Z9 65
U1 2
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUL 22
PY 2016
VL 6
AR 30226
DI 10.1038/srep30226
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA DR9GQ
UT WOS:000380205500001
PM 27444056
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Wei, H
   Xun, ZX
   Granado, H
   Wu, A
   Handa, JT
AF Wei, Hong
   Xun, Zixian
   Granado, Herta
   Wu, Angela
   Handa, James T.
TI An easy, rapid method to isolate RPE cell protein from the mouse eye
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Choroid; Dissection; Mouse; Retinal pigmented epithelium
AB The retinal pigment epithelium (RPE) is essential for maintaining the health of the neural retina. RPE cell dysfunction plays a critical role in many common blinding diseases including age-related macular degeneration (AMD), diabetic retinopathy, retinal dystrophies. Mouse models of ocular disease are commonly used to study these blinding diseases. Since isolating the RPE from the choroid has been challenging, most techniques separate the RPE from the retina, but not the choroid. As a result, the protein signature actually represents a heterogeneous population of cells that may not accurately represent the RPE response. Herein, we describe a method for separating proteins from the RPE that is free from retinal and choroidal contamination. After removing the anterior segment and retina from enucleated mouse eyes, protein from the RPE was extracted separately from the choroid by incubating the posterior eyecup with a protein lysis buffer for 10 min. Western blot analysis identified RPE65, an RPE specific protein in the RPE lysates, but not in choroidal lysates. The RPE lysates were devoid of rhodopsin and collagen VI, which are abundant in the retina and choroid, respectively. This technique will be very helpful for measuring the protein signal from the RPE without retinal or choroidal contamination. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Wei, Hong; Xun, Zixian; Granado, Herta; Wu, Angela; Handa, James T.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine
RP Handa, JT (通讯作者)，Smith Bldg,Room 3015,400 N Broadway, Baltimore, MD 21287 USA.
EM jthanda@jhmi.edu
FU NIH [EY14005, EY019044]; RPB Senior Scientist Award; RPB; 
   [P30EY001765]; NATIONAL EYE INSTITUTE [R01EY014005, R01EY019904,
   P30EY001765] Funding Source: NIH RePORTER
FX NIH EY14005 (JTH), EY019044 (JTH), RPB Senior Scientist Award (JTH),
   unrestricted award from RPB to the Wilmer Eye Institute; P30EY001765
   core grant, and a gift from the Merlau family and Aleda Wright. JTH is
   the Robert Bond Welch Professor.
CR Anderson NL, 2002, MOL CELL PROTEOMICS, V1, P845, DOI 10.1074/mcp.R200007-MCP200
   Boatright JH, 2015, MOL VIS, V21, P40
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NR 9
TC 30
Z9 30
U1 1
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD APR
PY 2016
VL 145
BP 450
EP 455
DI 10.1016/j.exer.2015.09.015
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DL1DL
UT WOS:000375372300051
PM 26424220
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Herrmann, P
   Cowing, JA
   Cristante, E
   Liyanage, SE
   Ribeiro, J
   Duran, Y
   Hervas, LA
   Carvalho, LS
   Bainbridge, JWB
   Luhmann, UFO
   Ali, RR
AF Herrmann, Philipp
   Cowing, Jill A.
   Cristante, Enrico
   Liyanage, Sidath E.
   Ribeiro, Joana
   Duran, Yanai
   Hervas, Laura Abelleira
   Carvalho, Livia S.
   Bainbridge, James W. B.
   Luhmann, Ulrich F. O.
   Ali, Robin R.
TI Cd59a deficiency in mice leads to preferential innate immune activation
   in the retinal pigment epithelium-choroid with age
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Cd59a; Complement regulator; Complement dysregulation; Age-related
   retinal degeneration; AMD; Aging
ID COMPLEMENT FACTOR-H; MACULAR DEGENERATION; REGULATORY PROTEIN;
   GENE-EXPRESSION; FACTOR B; INHIBITOR; INFLAMMATION; DRUSEN; CELLS;
   PATHOGENESIS
AB Dysregulation of the complement system has been implicated in the pathogenesis of age- related macular degeneration. To investigate consequences of altered complement regulation in the eye with age, we examined Cd59a complement regulator deficient (Cd59a(-/-)) mice between 4 and 15 months. In vivo imaging revealed an increased age- related accumulation of autofluorescent spots in Cd59a(-/-) mice, a feature that reflects accumulation of subretinal macrophages and/or microglia. Despite this activation of myeloid cells in the eye, Cd59a(-/-) mice showed normal retinal histology and function as well as normal choroidal microvasculature. With age, they revealed increased expression of activators of the alternative complement pathway (C3, Cfb, Cfd), in particular in the retinal pigment epithelium (RPE)-choroid but less in the retina. This molecular response was not altered by moderately-enhanced light exposure. Cd59a deficiency therefore leads to a preferential age-related dysregulation of the complement system in the RPE-choroid, that alone or in combination with light as a trigger, is not sufficient to cause choroidal vascular changes or retinal degeneration and dysfunction. This data emphasizes the particular vulnerability of the RPE-choroidal complex to dysregulation of the alternative complement pathway during aging. (C) 2015 The Authors. Published by Elsevier Inc.
C1 [Herrmann, Philipp; Cowing, Jill A.; Cristante, Enrico; Liyanage, Sidath E.; Ribeiro, Joana; Duran, Yanai; Hervas, Laura Abelleira; Carvalho, Livia S.; Bainbridge, James W. B.; Luhmann, Ulrich F. O.; Ali, Robin R.] UCL Inst Ophthalmol, Dept Genet, London EC1V 9EL, England.
   [Bainbridge, James W. B.; Ali, Robin R.] Moorfields Eye Hosp, NIHR Biomed Res Ctr Ophthalmol, London, England.
C3 University of London; University College London; University of London;
   University College London; Moorfields Eye Hospital NHS Foundation Trust
RP Luhmann, UFO (通讯作者)，UCL Inst Ophthalmol, Dept Genet, London EC1V 9EL, England.
EM u.luhmann@ucl.ac.uk
OI Luhmann, Ulrich F.O./0000-0002-1993-1951; Bainbridge,
   James/0000-0003-1318-8201; Ali, Robin/0000-0003-3126-6517; Claudio
   RIbeiro, Joana Filipa/0000-0002-9290-6023; Carvalho,
   Livia/0000-0002-3909-5778; Abelleira Hervas, Laura
   Esther/0000-0003-2423-8307
FU German Research Foundation (DFG) [He 6175/1-1]; Department of Health's
   National Institute for Health Research Biomedical Research Centre at
   Moorfields Eye Hospital; MRC [MR/K003003/1] Funding Source: UKRI;
   Medical Research Council [MR/K003003/1] Funding Source: researchfish;
   National Institute for Health Research [NF-SI-0513-10074,
   NIHR-RP-011-003] Funding Source: researchfish; Fight for Sight [1333/34]
   Funding Source: researchfish
FX The authors wish to thank Professor Paul Morgan for providing the
   Cd59a<SUP>-/-</SUP> mouse line. Furthermore, the authors wish to thank
   Dr. Magali Saint-Geniez for her help with the characterization of the
   choroidal vasculature. Philipp Herrmann is a fellow of the German
   Research Foundation (DFG He 6175/1-1). James W.B. Bainbridge and Robin
   R. Ali is partly funded by the Department of Health's National Institute
   for Health Research Biomedical Research Centre at Moorfields Eye
   Hospital. 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 12
Z9 13
U1 0
U2 9
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 SEP
PY 2015
VL 36
IS 9
BP 2637
EP 2648
DI 10.1016/j.neurobiolaging.2015.05.019
PG 12
WC Geriatrics & Gerontology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA CN9XI
UT WOS:000358803400020
PM 26234657
OA hybrid
DA 2022-11-30
ER

PT J
AU Alexander, P
   Thomson, HAJ
   Luff, AJ
   Lotery, AJ
AF Alexander, P.
   Thomson, H. A. J.
   Luff, A. J.
   Lotery, A. J.
TI Retinal pigment epithelium transplantation: concepts, challenges, and
   future prospects
SO EYE
LA English
DT Review
ID PLURIPOTENT STEM-CELLS; SEE VOL. 511; MACULAR DEGENERATION;
   PROLIFERATIVE VITREORETINOPATHY; RPE TRANSPLANTATION; VISUAL FUNCTIONS;
   MESSENGER-RNA; RCS RAT; PG. 112; TRANSLOCATION
AB The retinal pigment epithelium (RPE) is a single layer of cells that supports the light-sensitive photoreceptor cells that are essential for retinal function. Age-related macular degeneration (AMD) is a leading cause of visual impairment, and the primary pathogenic mechanism is thought to arise in the RPE layer. RPE cell structure and function are well understood, the cells are readily sustainable in laboratory culture and, unlike other cell types within the retina, RPE cells do not require synaptic connections to perform their role. These factors, together with the relative ease of outer retinal imaging, make RPE cells an attractive target for cell transplantation compared with other cell types in the retina or central nervous system. Seminal experiments in rats with an inherited RPE dystrophy have demonstrated that RPE transplantation can prevent photoreceptor loss and maintain visual function. This review provides an update on the progress made so far on RPE transplantation in human eyes, outlines potential sources of donor cells, and describes the technical and surgical challenges faced by the transplanting surgeon. Recent advances in the understanding of pluripotent stem cells, combined with novel surgical instrumentation, hold considerable promise, and support the concept of RPE transplantation as a regenerative strategy in AMD.
C1 [Alexander, P.; Thomson, H. A. J.; Luff, A. J.; Lotery, A. J.] Univ Southampton, Southampton Univ Hosp, Fac Med, Clin Neurosci Res Grp,Clin & Expt Sci, Southampton SO16 6YD, Hants, England.
C3 University of Southampton
RP Lotery, AJ (通讯作者)，Univ Southampton, Southampton Univ Hosp, Fac Med, Ophthalmol, South Lab & Path Block,Mailpoint 806,Level D, Southampton SO16 6YD, Hants, England.
EM a.j.lotery@soton.ac.uk
FU Brian Mercer Charitable Trust; Global Ophthalmology Awards Program from
   Bayer
FX We are grateful to Dr Miguel Velazquez and Mr Alan Morris for their
   assistance with the illustrations in this article. We acknowledge
   funding support from the Brian Mercer Charitable Trust and the Global
   Ophthalmology Awards Program from Bayer.
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NR 84
TC 39
Z9 44
U1 0
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD AUG
PY 2015
VL 29
IS 8
BP 992
EP 1002
DI 10.1038/eye.2015.89
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CO9GF
UT WOS:000359481500003
PM 26043704
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Yao, J
   Ko, CW
   Baranov, PY
   Regatieri, CV
   Redenti, S
   Tucker, BA
   Mighty, J
   Tao, SL
   Young, MJ
AF Yao, Jing
   Ko, Chi Wan
   Baranov, Petr Y.
   Regatieri, Caio V.
   Redenti, Stephen
   Tucker, Budd A.
   Mighty, Jason
   Tao, Sarah L.
   Young, Michael J.
TI Enhanced Differentiation and Delivery of Mouse Retinal Progenitor Cells
   Using a Micropatterned Biodegradable Thin-Film Polycaprolactone Scaffold
SO TISSUE ENGINEERING PART A
LA English
DT Article
ID GENE-EXPRESSION; TRANSPLANTATION; GENERATION; STIFFNESS;
   MECHANOTRANSDUCTION; PHOTORECEPTORS; FABRICATION; INTEGRATION;
   MODULATION; SURVIVAL
AB The deterioration of retinal tissue in advanced stages of retinitis pigmentosa and age-related macular degeneration and the lack of signaling cues for laminar regeneration are significant challenges highlighting the need for a tissue engineering approach to retinal repair. In this study, we fabricated a biodegradable thin-film polycaprolactone (PCL) scaffold with varying surface topographies using microfabrication techniques. Mouse retinal progenitor cells (mRPCs) cultured on PCL scaffolds exhibited enhanced potential to differentiate toward a photoreceptor fate in comparison to mRPCs cultured on control substrates, suggesting that PCL scaffolds are promising as substrates to guide differentiation of mRPCs toward a photoreceptor fate in vitro before transplantation. When cocultured with the retinal explants of rhodopsin null mice, mRPC/PCL constructs showed increased mRPC integration rates compared to directly applied dissociated mRPCs. Moreover, these mRPC/PCL constructs could be delivered into the subretinal space of rhodopsin null mice with minimal disturbance of the host retina. Whether cocultured with retinal explants or transplanted into the subretinal space, newly integrated mRPCs localized to the outer nuclear layer and expressed appropriate markers of photoreceptor fate. Thus, the PCL scaffold provides a platform to guide differentiation and organized delivery of mRPCs as a practical strategy to repair damaged retina.
C1 [Yao, Jing] Fudan Univ, Shanghai Med Sch, Eye & ENT Hosp, Dept Ophthalmol, Shanghai 200433, Peoples R China.
   [Yao, Jing; Baranov, Petr Y.; Regatieri, Caio V.; Tucker, Budd A.; Young, Michael J.] Harvard Univ, Massachusetts Eye & Ear, Schepens Eye Res Inst, Dept Ophthalmol,Sch Med, Boston, MA 02114 USA.
   [Ko, Chi Wan; Tao, Sarah L.] Charles Stark Draper Lab Inc, Cambridge, MA USA.
   [Ko, Chi Wan] MIT, Dept Mech Engn, Cambridge, MA 02139 USA.
   [Redenti, Stephen; Mighty, Jason] CUNY, Lehman Coll, Dept Biol Sci, Bronx, NY USA.
C3 Fudan University; Harvard University; Harvard Medical School;
   Massachusetts Eye & Ear Infirmary; Schepens Eye Research Institute; The
   Charles Stark Draper Laboratory, Inc.; Massachusetts Institute of
   Technology (MIT); City University of New York (CUNY) System; Lehman
   College (CUNY)
RP Young, MJ (通讯作者)，Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, 20 Staniford St, Boston, MA 02114 USA.
EM mchael_young@meei.harvard.edu
RI Regatieri, Caio/G-8152-2014
OI Regatieri, Caio/0000-0003-1511-8696; Tucker, Budd/0000-0003-2178-1742
FU Lincy Fundation Discovery Eye Foundation; Grousbeck Foundation (Cep290
   Consortium)
FX We would like to thank Peter Humphries (Trinity College, Dublin) for
   providing Rho-/-mouse breeding pairs, D.F. Chen (Harvard Medical School)
   for helpful suggestions, and D. Pottle, S. Qi, M. Saint-Geniez, K.S. Cho
   (Harvard Medical School) for technical assistance. Financial support was
   provided by the Lincy Fundation Discovery Eye Foundation, Grousbeck
   Foundation (Cep290 Consortium).
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NR 46
TC 37
Z9 37
U1 1
U2 28
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3341
EI 1937-335X
J9 TISSUE ENG PT A
JI Tissue Eng. Part A
PD APR 1
PY 2015
VL 21
IS 7-8
BP 1247
EP 1260
DI 10.1089/ten.tea.2013.0720
PG 14
WC Cell & Tissue Engineering; Cell Biology; Engineering, Biomedical;
   Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Engineering; Materials Science
GA CF5RC
UT WOS:000352613600007
PM 25517296
OA Green Published
DA 2022-11-30
ER

PT J
AU Heller, JP
   Martin, KR
AF Heller, Janosch P.
   Martin, Keith R.
TI Enhancing RPE Cell-Based Therapy Outcomes for AMD: The Role of Bruch's
   Membrane
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Review
DE age-related macular degeneration; retinal pigment epithelium; integrin
ID RETINAL-PIGMENT EPITHELIUM; PLURIPOTENT STEM-CELLS; CHONDROITIN SULFATE
   PROTEOGLYCANS; MACULAR DEGENERATION; INTEGRIN ACTIVATION;
   EXTRACELLULAR-MATRIX; SHORT-TERM; RCS RAT; AUTOLOGOUS TRANSPLANTATION;
   VISUAL FUNCTION
AB Age-related macular degeneration (AMD) is the leading cause of legal blindness in older people in the developed world. The disease involves damage to the part of the retina responsible for central vision. Degeneration of retinal pigment epithelial (RPE) cells, photoreceptors, and choriocapillaris may contribute to visual loss. Over the past decades, scientists and clinicians have tried to replace lost RPE cells in patients with AMD using cells from different sources. In recent years, advances in generating RPE cells from stem cells have been made and clinical trials are currently evaluating the safety and efficiency of replacing the degenerated RPE cell layer with stem cell-derived RPE cells. However, the therapeutic success of transplantation of stem cell-derived RPE cells may be limited unless the transplanted cells can adhere and survive in the long term in the diseased eye. One hallmark of AMD is the altered extracellular environment of Bruch's membrane to which the grafted cells have to adhere. Here, we discuss recent approaches to overcome the inhibitory environment of the diseased eye and to enhance the survival rate of transplanted RPE cells. Our aim is to highlight novel approaches that may have the potential to improve the efficacy of RPE transplantation for AMD in the future.
C1 [Heller, Janosch P.; Martin, Keith R.] Univ Cambridge, Dept Clin Neurosci, John van Geest Ctr Brain Repair, Cambridge CB2 0PY, England.
   [Heller, Janosch P.] UCL, Inst Neurol, Dept Clin & Expt Epilepsy, London WC1E 6BT, England.
   [Martin, Keith R.] Univ Cambridge, Dept Ophthalmol, NIHR Biomed Res Ctr, Cambridge, England.
   [Martin, Keith R.] Univ Cambridge, Wellcome Trust MRC Cambridge Stem Cell Inst, Cambridge, England.
C3 University of Cambridge; University of London; University College
   London; University of Cambridge; University of Cambridge
RP Martin, KR (通讯作者)，Univ Cambridge, Dept Clin Neurosci, John van Geest Ctr Brain Repair, Cambridge CB2 0PY, England.
EM krgm2@cam.ac.uk
RI Heller, Janosch/J-7509-2019; Heller, Janosch/GVT-5921-2022
OI Heller, Janosch/0000-0002-8825-3787; 
FU Wellcome Trust [97922] Funding Source: Medline
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NR 181
TC 26
Z9 26
U1 0
U2 5
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 2164-2591
J9 TRANSL VIS SCI TECHN
JI Transl. Vis. Sci. Technol.
PD JUL
PY 2014
VL 3
IS 4
AR 4
DI 10.1167/tvst.3.4.4
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA V45JU
UT WOS:000209813700004
PM 25068093
DA 2022-11-30
ER

PT J
AU Kyosseva, SV
   Chen, LJ
   Seal, S
   McGinnis, JF
AF Kyosseva, Svetlana V.
   Chen, Lijuan
   Seal, Sudipta
   McGinnis, James F.
TI Nanoceria inhibit expression of genes associated with inflammation and
   angiogenesis in the retina of Vldlr null mice
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE nanoceria; oxidative stress; inflammation; Vldlr mouse; age related
   macular degeneration; PCR array
ID DENSITY LIPOPROTEIN RECEPTOR; CERIUM OXIDE NANOPARTICLES; ENDOTHELIAL
   GROWTH-FACTOR; MACULAR DEGENERATION; SUBRETINAL NEOVASCULARIZATION;
   CORNEAL EPITHELIUM; OXIDATIVE STRESS; UP-REGULATION; MOUSE MODEL;
   PATHOGENESIS
AB Oxidative stress and inflammation are important pathological mechanisms in many neurodegenerative diseases, including age-related macular degeneration (AMD). The very low-density lipoprotein receptor knockout mouse (Vldlr-/-) has been identified as a model for AMD and in particular for retinal angiomatous proliferation (RAP). In this study we examined the effect of cerium oxide nanoparticles (nanoceria) that have been shown to have catalytic antioxidant activity, on expression of 88 major cytokines in the retinas of Vldlr-/- mice using a PCR array. A single intravitreal injection of nanoceria at P28 caused inhibition of pro-inflammatory cytokines and pro-angiogenic growth factors including Tslp, Lif, Il3, Il7, Vegfa, Fgf1, Fgf2, Fgf7, Egf, Efna3, Lep, and up-regulation of several cytokines and anti-angiogenic genes in the Vldlr-/- retina within one week. We used the Ingenuity Pathway Analysis software to search for biological functions, pathways, and interrelationships between gene networks. Many of the genes whose activities were affected are involved in cell signaling, cellular development, growth and proliferation, and tissue development. Western blot analysis revealed that nanoceria inhibit the activation of ERK 1/2, JNK, p38 MAP kinase, and Akt. These data suggest that nanoceria may represent a novel therapeutic strategy to treat AMD, RAP, and other neurodegenerative diseases. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Kyosseva, Svetlana V.; Chen, Lijuan; McGinnis, James F.] Univ Oklahoma, Dean McGee Eye Inst, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK 73104 USA.
   [McGinnis, James F.] Univ Oklahoma, Dept Cell Biol, Hlth Sci Ctr, Oklahoma City, OK 73104 USA.
   [Seal, Sudipta] Univ Cent Florida, Adv Mat Proc Anal Ctr, Nanosci & Technol Ctr, Orlando, FL 32816 USA.
C3 University of Oklahoma System; University of Oklahoma Health Sciences
   Center; University of Oklahoma System; University of Oklahoma Health
   Sciences Center; State University System of Florida; University of
   Central Florida
RP Kyosseva, SV (通讯作者)，Univ Arkansas Med Sci, Dept Biochem & Mol Biol, 4301 West Markham St, Little Rock, AR 72205 USA.
EM svkiosseva@uams.edu; james-mcginnis@ouhsc.edu
RI Seal, Sudipta/A-7698-2012; Nanozymes, Nanozymes/D-8197-2019
FU NIH [P30-EY12190, COBRE-P20 RR017703, R21EY018306, R01EY018724]; FFB
   [C-NP-0707-0404-UOK08, NSF: CBET-0708172, OCAST: HR06-075]; Presbyterian
   Health Foundation; Research to Prevent Blindness (RPB); RPB Senior
   Scientific Investigator Award; NATIONAL CENTER FOR RESEARCH RESOURCES
   [P20RR017703] Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE
   [R01EY018724, R01EY022111, P30EY012190, R21EY018306] Funding Source: NIH
   RePORTER
FX This work was supported by grants from: NIH (P30-EY12190, COBRE-P20
   RR017703, R21EY018306, R01EY018724); FFB (C-NP-0707-0404-UOK08; NSF:
   CBET-0708172; OCAST: HR06-075), and unrestricted funds from Presbyterian
   Health Foundation and Research to Prevent Blindness (RPB). JFM is a
   recipient of an RPB Senior Scientific Investigator Award.
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NR 75
TC 55
Z9 57
U1 2
U2 28
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD NOV
PY 2013
VL 116
BP 63
EP 74
DI 10.1016/j.exer.2013.08.003
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 259YP
UT WOS:000327562500009
PM 23978600
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Nuzzi, R
   Gunetti, M
   Rustichelli, D
   Roagna, B
   Bardelli, FF
   Fagioli, F
   Ferrero, I
AF Nuzzi, Raffaele
   Gunetti, Monica
   Rustichelli, Deborah
   Roagna, Barbara
   Bardelli, Francesca Fronticelli
   Fagioli, Franca
   Ferrero, Ivana
TI Effect of In Vitro Exposure of Corticosteroid Drugs, Conventionally Used
   in AMD Treatment, on Mesenchymal Stem Cells
SO STEM CELLS INTERNATIONAL
LA English
DT Article
ID TRIAMCINOLONE ACETONIDE; STROMAL CELLS; THERAPY; DIFFERENTIATION;
   TRANSPLANTATION; PHOTORECEPTORS; DEXAMETHASONE; DEGENERATION; MODEL
AB Age-related macular degeneration (AMD) is a leading cause of legal blindness in individuals over 60 years of age, characterized by the dysfunction of retinal pigmented epithelium cells, specifically in the macular area. Despite several treatment options, AMD therapy remains difficult, especially for exudative AMD. Multipotent mesenchymal stem cells (MSCs), with great plasticity and immunomodulant properties, are a promising cell source for cellular therapy and tissue engineering. We evaluated the effects of steroid drugs, often used to treat AMD, in association with MSCs, in view of a possible application together to treat AMD. Morphology, viability, growth kinetics, and immunophenotype were evaluated on healthy donors' MSCs, treated with triamcinolone acetonide, alcohol-free triamcinolone acetonide, micronized intravitreal triamcinolone and dexamethasone at different concentrations, and in a human retinal pigment epithelial cell line supernatant (ARPE-19). The morphological analysis of MSCs in their standard medium showed a negative correlation with drug concentrations, due to the numerous crystals. Dexamethasone was the least toxic corticosteroid used in this study. ARPE-19 seemed to help cells preserve the typical MSC morphology. In conclusion, this in vitro study demonstrated that high doses of corticosteroid drugs have a negative effect on MSCs, reduced in the presence of a conditioned media.
C1 [Nuzzi, Raffaele; Roagna, Barbara; Bardelli, Francesca Fronticelli] Univ Turin, Ophthalmol Sect, Dept Clin Pathophysiol, I-10126 Turin, Italy.
   [Gunetti, Monica; Rustichelli, Deborah; Fagioli, Franca; Ferrero, Ivana] Regina Margherita Childrens Hosp, Stem Cell Transplantat & Cellular Therapy Div, I-10126 Turin, Italy.
   [Ferrero, Ivana] Univ Turin, Dept Pediat, I-10126 Turin, Italy.
C3 University of Turin; A.O.U. Citta della Salute e della Scienza di
   Torino; University of Turin
RP Ferrero, I (通讯作者)，Regina Margherita Childrens Hosp, Stem Cell Transplantat & Cellular Therapy Div, I-10126 Turin, Italy.
EM ivana.ferrero@unito.it
RI Gunetti, Monica/AAA-7815-2020; Fagioli, Franca/AAC-2181-2022; Ferrero,
   Ivana/AAC-2302-2022
OI Gunetti, Monica/0000-0002-7466-4972; Nuzzi,
   Raffaele/0000-0002-5381-832X; FAGIOLI, FRANCA/0000-0002-9257-900X;
   FERRERO, Ivana/0000-0002-4364-8021
FU Regione Piemonte
FX The authors are also grateful to Andrew Martin Garvey, BA (Hons), LTCL
   (TESOL), PGCPolSci, for editorial assistance. This work was supported by
   Regione Piemonte.
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NR 27
TC 18
Z9 19
U1 0
U2 6
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 1687-966X
EI 1687-9678
J9 STEM CELLS INT
JI Stem Cells Int.
PY 2012
VL 2012
AR 946090
DI 10.1155/2012/946090
PG 11
WC Cell & Tissue Engineering
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 209UX
UT WOS:000323786800001
PM 22693520
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Muzyka-Wozniak, M
AF Muzyka-Wozniak, Maria
TI Phacoemulsification in eyes with neovascular AMD treated with anti-VEGF
   injections
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Anti-VEGF injections; Cataract; Neovascular age-related macular
   degeneration; Optical coherence tomography
ID AGE-RELATED MACULOPATHY; EXTRACAPSULAR CATARACT-EXTRACTION; BLUE
   MOUNTAINS EYE; MACULAR DEGENERATION; BEAVER DAM; SURGERY; PROGRESSION;
   REGIMEN; RISK
AB PURPOSE. To evaluate visual results of phacoemulsification in eyes with neovascular age-related macular degeneration (AMD) treated with anti-vascular endothelial growth factor (VEGF) intravitreal injections.
   METHODS. This retrospective noncomparative interventional case-series study assessed best-corrected visual acuity (BCVA) at 4 timepoints: 1) baseline, immediately before first anti-VEGF injection; 2) preoperative, immediately before phacoemulsification; 3) postoperative, 1 month after phacoemulsification; 4) endpoint, at the last visit. Anti-VEGF retreatment regimen was based only on optical coherence tomography. The median time between anti-VEGF injections was evaluated for the time period before and after phacoemulsification.
   RESULTS. Sixteen eyes of 16 patients were included. The median (range) baseline, preoperative, postoperative, and endpoint BCVA was 0.7 (0.3-1.3), 0.72 (0.4-1.3), 0.5 (0.05-1.0), and 0.36 (0.0-1.0) logMAR, respectively. Best-corrected visual acuity significantly improved after phacoemulsification (mean 3 logMAR lines) and remained stable during follow-up (median 14 months, range 7-28). There was no statistically significant difference in the median time interval between injections before phacoemulsification and after phacoemulsification.
   CONCLUSIONS. Phacoemulsification significantly improved BCVA in patients with choroidal neovascular AMD. This effect persisted during follow-up with no increased need for anti-VEGF injections to keep macula dry.
C1 [Muzyka-Wozniak, Maria] Wroclaw Med Univ, Dept Ophthalmol, Wroclaw, Poland.
C3 Wroclaw Medical University
RP Muzyka-Wozniak, M (通讯作者)，Promien 12, PL-51659 Wroclaw, Poland.
EM maria-muzyka@tlen.pl
RI Muzyka-Woźniak, Maria/AAF-2849-2021
OI Muzyka-Wozniak, Maria/0000-0002-4666-2400
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NR 16
TC 13
Z9 13
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 NOV-DEC
PY 2011
VL 21
IS 6
BP 766
EP 770
DI 10.5301/EJO.2011.6389
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 926YF
UT WOS:000302868300013
PM 21360482
DA 2022-11-30
ER

PT J
AU Liu, MM
   Tuo, JS
   Chan, CC
AF Liu, Melissa M.
   Tuo, Jingsheng
   Chan, Chi-Chao
TI Republished review: Gene therapy for ocular diseases
SO POSTGRADUATE MEDICAL JOURNAL
LA English
DT Review
ID EPITHELIUM-DERIVED FACTOR; CILIARY NEUROTROPHIC FACTOR; RETINAL
   GANGLION-CELLS; LEBER CONGENITAL AMAUROSIS; ADENOVIRUS-MEDIATED
   DELIVERY; RCS RAT MODEL; MOUSE MODEL; ADENOASSOCIATED VIRUS; TRANSGENE
   EXPRESSION; PHOTORECEPTOR DEGENERATION
AB The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus-and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.
C1 [Liu, Melissa M.; Tuo, Jingsheng; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20895 USA.
C3 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,Bldg 10,Rm 10N103, Bethesda, MD 20895 USA.
EM chanc@nei.nih.gov
OI Tuo, Jingsheng/0000-0002-1372-7810
FU NEI; American Health Assistance Foundation [M2007037]; National
   Institutes of Health; NATIONAL EYE INSTITUTE [ZIAEY000418, ZIAEY000222,
   T32EY007143] Funding Source: NIH RePORTER
FX This work was supported by the NEI Intramural Research Program and the
   American Health Assistance Foundation (M2007037). Other Funders:
   National Institutes of Health.
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NR 104
TC 12
Z9 15
U1 0
U2 10
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0032-5473
EI 1469-0756
J9 POSTGRAD MED J
JI Postgrad. Med. J.
PD JUL
PY 2011
VL 87
IS 1029
BP 487
EP 495
DI 10.1136/pgmj.2009.174912rep
PG 9
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 782TV
UT WOS:000292035700010
PM 21705775
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Gandhi, J
   Cashman, SM
   Kumar-Singh, R
AF Gandhi, Jarel
   Cashman, Siobhan M.
   Kumar-Singh, Rajendra
TI Soluble CD59 Expressed from an Adenovirus In Vivo Is a Potent Inhibitor
   of Complement Deposition on Murine Liver Vascular Endothelium
SO PLOS ONE
LA English
DT Article
ID MEMBRANE ATTACK COMPLEX; MACULAR DEGENERATION; REGULATOR CD59; TARGETED
   FORM; FACTOR-H; RECOMBINANT; DEFICIENCY; ACTIVATION; DISEASE; SYSTEM
AB Inappropriate activation of complement on the vascular endothelium of specific organs, or systemically, underlies the etiology of a number of diseases. These disorders include atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis, atherosclerosis, age-related macular degeneration, diabetic retinopathy, and transplant rejection. Inhibition of the terminal step of complement activation, i.e. formation of the membrane attack complex, using CD59 has the advantage of retaining the upstream processes of the complement cascade necessary for fighting pathogens and retaining complement's crucial role in tissue homeostasis. Previous studies have shown the necessity of membrane targeting of soluble CD59 in order for it to prove an effective inhibitor of complement deposition both in vitro and in vivo. In this study we have generated an in vivo model of human complement activation on murine liver vascular endothelium. This model should prove useful for the development of anti-complement therapies for complement-induced pathologies of vascular endothelium. Using this model, we have demonstrated the viability of a non membrane-targeted soluble CD59 to significantly inhibit complement deposition on the endothelium of murine liver vasculature when expressed in vivo from an adenovirus. This result, unanticipated based on prior studies, suggests that the use of non membrane-targeted sCD59 as an anti-complement therapy be re-visited.
C1 [Gandhi, Jarel; Cashman, Siobhan M.; Kumar-Singh, Rajendra] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA.
C3 Tufts University
RP Gandhi, J (通讯作者)，Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA.
EM rajendra.kumar-singh@tufts.edu
OI Kumar-Singh, Rajendra/0000-0002-7754-0713
FU The Ellison Foundation; Virginia B. Smith Trust; NIH/NEI [EY014991,
   EY013887]; Lions Eye Foundation; Research to Prevent Blindness; NATIONAL
   EYE INSTITUTE [R01EY014991] Funding Source: NIH RePORTER
FX This study was supported by grants to R.K.-S. from The Ellison
   Foundation, The Virginia B. Smith Trust, NIH/NEI (EY014991 and EY013887)
   and grants to the Department of Ophthalmology at Tufts University from
   the Lions Eye Foundation and Research to Prevent Blindness. The funders
   had no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript.
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NR 40
TC 9
Z9 11
U1 1
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 24
PY 2011
VL 6
IS 6
AR e21621
DI 10.1371/journal.pone.0021621
PG 8
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 782UF
UT WOS:000292036900061
PM 21720565
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Zhou, XH
   Wong, LL
   Karakoti, AS
   Seal, S
   McGinnis, JF
AF Zhou, Xiaohong
   Wong, Lily L.
   Karakoti, Ajay S.
   Seal, Sudipta
   McGinnis, James F.
TI Nanoceria Inhibit the Development and Promote the Regression of
   Pathologic Retinal Neovascularization in the Vldlr Knockout Mouse
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; OXIDATIVE STRESS; NADPH OXIDASE; SUBRETINAL
   NEOVASCULARIZATION; PHOTORECEPTOR DEGENERATION; PIGMENT EPITHELIUM;
   MODEL; MICE; PROTECTION; INJURY
AB Many neurodegenerative diseases are known to occur and progress because of oxidative stress, the presence of reactive oxygen species (ROS) in excess of the cellular defensive capabilities. Age related macular degeneration (AMD), diabetic retinopathy (DR) and inherited retinal degeneration share oxidative stress as a common node upstream of the blinding effects of these diseases. Knockout of the Vldlr gene results in a mouse that develops intraretinal and subretinal neovascular lesions within the first month of age and is an excellent model for a form of AMD called retinal angiomatous proliferation (RAP). Cerium oxide nanoparticles (nanoceria) catalytically scavenge ROS by mimicking the activities of superoxide dismutase and catalase. A single intravitreal injection of nanoceria into the Vldlr-/- eye was shown to inhibit: the rise in ROS in the Vldlr-/- retina, increases in vascular endothelial growth factor (VEGF) in the photoreceptor layer, and the formation of intraretinal and subretinal neovascular lesions. Of more therapeutic interest, injection of nanoceria into older mice (postnatal day 28) resulted in the regression of existing vascular lesions indicating that the pathologic neovessels require the continual production of excessive ROS. Our data demonstrate the unique ability of nanoceria to prevent downstream effects of oxidative stress in vivo and support their therapeutic potential for treatment of neurodegenerative diseases such as AMD and DR.
C1 [Zhou, Xiaohong; Wong, Lily L.; Karakoti, Ajay S.; Seal, Sudipta; McGinnis, James F.] Univ Oklahoma, Coll Med, Dept Ophthalmol, Dean McGee Eye Inst, Oklahoma City, OK 73190 USA.
   [Karakoti, Ajay S.; Seal, Sudipta] Univ Cent Florida, Adv Mat Proc Anal Ctr, Mech Mat Aerosp Engn Nanosci & Technol Ctr, Orlando, FL 32816 USA.
   [McGinnis, James F.] Oklahoma Ctr Neurosci, Dept Ophthalmol & Cell Biol, Oklahoma City, OK USA.
C3 University of Oklahoma System; University of Oklahoma Health Sciences
   Center; State University System of Florida; University of Central
   Florida
RP Zhou, XH (通讯作者)，Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Howe Lab, Boston, MA 02115 USA.
EM lily-wong@ouhsc.edu; james-mcginnis@ouhsc.edu
RI Nanozymes, Nanozymes/D-8197-2019; Karakoti, Ajay/AGI-8160-2022; Wong, Li
   Lian/AAG-5568-2020; Seal, Sudipta/A-7698-2012; Liu,
   Zhanjiang/R-9633-2019; Karakoti, Ajay/AAY-5886-2020; Wong,
   Lily/D-7737-2011
OI Wong, Li Lian/0000-0001-9045-4556; Na-Nakorn,
   Uthairat/0000-0002-0804-3561; KARAKOTI, AJAY/0000-0001-9081-2325; Wong,
   Lily/0000-0003-0569-3398
FU NIH [P30-EY12190, COBRE-P20 RR017703, R21EY018306, R01EY018724]; FFB
   [C-NP-0707-0404-UOK08]; NSF [CBET-0708172]; OCAST [HR06-075];
   Presbyterian Health Foundation; Research to Prevent Blindness; RPB;
   NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR017703] Funding Source: NIH
   RePORTER; NATIONAL EYE INSTITUTE [P30EY012190, R21EY018306, R01EY018724]
   Funding Source: NIH RePORTER
FX This work was supported by grants from: NIH: P30-EY12190, COBRE-P20
   RR017703, R21EY018306, R01EY018724; FFB (http://www.blindness.org/):
   C-NP-0707-0404-UOK08; NSF: CBET-0708172;
   OCAST(http://www.ok.gov/ocast/Programs/Oklahoma_Health_Research_(OHR)/in
   dex.html): HR06-075, and unrestricted funds from Presbyterian Health
   Foundation (http://www.phfokc.com/research.htm) and Research to Prevent
   Blindness (http://www.rpbusa.org/rpb/) (RPB). JFM is a recipient of an
   RPB Senior Scientific Investigator Award. The funders had no role in
   study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
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NR 50
TC 161
Z9 171
U1 2
U2 39
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 22
PY 2011
VL 6
IS 2
AR e16733
DI 10.1371/journal.pone.0016733
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 725PA
UT WOS:000287656600014
PM 21423623
OA gold, Green Submitted, Green Published
DA 2022-11-30
ER

PT J
AU Schmidt-Erfurth, UM
   Stock, G
   Pruente, C
   Ahlers, C
AF Schmidt-Erfurth, Ursula Margarethe
   Stock, Geraldine
   Pruente, Christian
   Ahlers, Christian
TI Three-dimensional angiographic imaging of leakage in branch retinal vein
   occlusion
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE branch retinal vein occlusion; leakage; topographic angiography;
   vascular occlusion
ID OPTICAL COHERENCE TOMOGRAPHY; RHESUS-MONKEYS; TOPOGRAPHIC ANGIOGRAPHY
AB Purpose:
   Optical coherence tomography (OCT) is used to image branch retinal vein occlusion (BRVO) but lacks information about leakage dynamics and perfusion status. Topographical angiography (TAG) is capable of providing this information and has been described previously in age-related macular degeneration. This study evaluates TAG in BRVO.
   Methods:
   We included 56 eyes of 40 consecutive patients with BRVO and a reduction in central vision. Two groups were established based on whether argon laser coagulation was performed or not. A standardized follow-up was performed. The chorioretinal fluorescence pattern was reconstructed following TAG. Quantitative measurements were also performed.
   Results:
   TAG performed from indocyanine green angiography (ICGA) showed smaller lesion size (LS) compared to fluorescein angiography (FA) (mean difference: early phase = -1.6 mm2, late phase = -1.8 mm2). The extent of mean LS from early to late phase increased by 0.8 mm2 in FA and by 0.6 mm2 in ICGA. TAG could visualize different degrees of leakage topographically.
   Conclusion:
   TAG gives new insights into the pathophysiology of BRVO: it enables the visualization of dynamics of leakage and the demonstration of the effects of intravasal stasis. Furthermore, TAG is less impaired by masking phenomena than FA. Functional retinal imaging shows distinct advantages over OCT: quantification of leakage activity is possible using TAG.
C1 [Schmidt-Erfurth, Ursula Margarethe; Stock, Geraldine; Pruente, Christian; Ahlers, Christian] Med Univ Vienna, Dept Ophthalmol, A-1090 Vienna, Austria.
C3 Medical University of Vienna
RP Schmidt-Erfurth, UM (通讯作者)，Med Univ Vienna, Dept Ophthalmol, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM ursula.schmidt-erfurth@meduniwien.ac.at
OI Schmidt-Erfurth, Ursula/0000-0002-7788-7311
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NR 20
TC 0
Z9 0
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 MAR
PY 2010
VL 88
IS 2
BP 181
EP 187
DI 10.1111/j.1755-3768.2008.01390.x
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 560WB
UT WOS:000274933700034
PM 18937811
DA 2022-11-30
ER

PT J
AU Dunaief, JL
   Richa, C
   Franks, EP
   Schultze, RL
   Aleman, TS
   Schenck, JF
   Zimmerman, EA
   Brooks, DG
AF Dunaief, JL
   Richa, C
   Franks, EP
   Schultze, RL
   Aleman, TS
   Schenck, JF
   Zimmerman, EA
   Brooks, DG
TI Macular degeneration in a patient with aceruloplasminemia, a disease
   associated with retinal iron overload
SO OPHTHALMOLOGY
LA English
DT Article
ID HEREDITARY CERULOPLASMIN DEFICIENCY; EFFLUX; DISRUPTION
AB Purpose: To provide the first ophthalmic case report of a Caucasian patient with the rare autosomal recessive disease aceruloplasminemia, which results in iron overload in the retina, brain, and pancreas.
   Design: Single observational case report.
   Methods: Perls' staining of a conjunctival biopsy was used to detect elevated iron levels in the conjunctival epithelium. Fundus photography, fluorescein angiography, and electroretinography were used to document retinal appearance and function.
   Results: Unlike a report of a Japanese patient with aceruloplasminemia, who had midperipheral retinal pigment epithelium (RPE) cell atrophy and yellowish discoloration of the fundus, our Caucasian patient had a maculopathy. Beginning at age 47, he had development and progression of multiple subretinal yellowish-white lesions and RPE cell atrophy. To confirm tissue iron overload in our patient, we took the novel approach of a conjunctival biopsy, which showed Perls' Prussian blue-positive epithelial cells.
   Conclusions: Given our recent finding of elevated iron levels in the RPE of patients with age-related macular degeneration (AMD), it is interesting that retinal iron overload in aceruloplasminemia is associated with a maculopathy that clinically resembles AMD. This finding supports the hypothesis that retinal iron homeostasis is essential for normal retinal function. Disruption of iron homeostasis could contribute to the pathogenesis of AMD.
C1 FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA USA.
   Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA.
   GE Global Res, Magnet Resonance Imaging Lab, Niskayuna, NY USA.
   Albany Med Coll, Dept Neurol, Albany, NY 12208 USA.
   Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; Pennsylvania Medicine; University of
   Pennsylvania; Pennsylvania Medicine; General Electric; Albany Medical
   College; University of Pennsylvania
RP Dunaief, JL (通讯作者)，Stellar Chance Labs 305, 422 Curie Blvd, Philadelphia, PA 19104 USA.
EM jdunaief@mail.med.upenn.edu
FU NEI NIH HHS [EY015240, EY00417] Funding Source: Medline; NATIONAL EYE
   INSTITUTE [R01EY015240] Funding Source: NIH RePORTER
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NR 13
TC 92
Z9 100
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
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUN
PY 2005
VL 112
IS 6
BP 1062
EP 1065
DI 10.1016/j.ophtha.2004.12.029
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 932CI
UT WOS:000229531400018
PM 15882908
DA 2022-11-30
ER

PT J
AU Das, A
   McGuire, PG
AF Das, A
   McGuire, PG
TI Retinal and choroidal angiogenesis: pathophysiology and strategies for
   inhibition
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
DE angiogenesis; retinal neovascularization; choroidal neovascularization
ID ENDOTHELIAL GROWTH-FACTOR; EPITHELIUM-DERIVED FACTOR;
   PLASMINOGEN-ACTIVATOR INHIBITOR; OXYGEN-INDUCED RETINOPATHY;
   VASCULAR-PERMEABILITY FACTOR; PROLIFERATIVE DIABETIC-RETINOPATHY;
   MESSENGER-RNA EXPRESSION; TUMOR-NECROSIS-FACTOR;
   MATRIX-METALLOPROTEINASE; IN-VIVO
AB Retinal angiogenesis and choroidal angiogenesis are major causes of vision loss, and the pathogenesis of this angiogenesis process is still uncertain. However, several key steps of the angiogenic cascade have been elucidated. In retinal angiogenesis, hypoxia is the initial stimulus that causes up regulation of growth factors, integrins and proteinases, which result in endothelial cell proliferation and migration that are critical steps in this process. Once the endothelial tube is formed from the existing blood vessels, maturation starts with recruitment of mural cell precursors and formation of the basement membrane. Normally, there is a tight balance between angiogenic factors and endogenous angiogenesis inhibitors that help to keep the angiogenic process under control. Although the steps of choroidal angiogenesis seem to be similar to those of retinal angiogenesis, there are some major differences between these two processes. Several anti-angiogenic approaches are being developed in animal models to prevent ocular angiogenesis by blocking the key steps of the angiogenic cascade. Based on these pre-clinical studies, several anti-angiogenic clinical trials are ongoing in patients with diabetic retinopathy and age-related macular degeneration. This review discusses the pathogenesis of retinal and choroidal angiogenesis, and alternative pharmacological approaches to inhibit angiogenesis in ocular diseases. Published by Elsevier Ltd.
C1 Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA.
   New Mexico VA Hlth Care Syst, Albuquerque, NM USA.
C3 University of New Mexico
RP Das, A (通讯作者)，Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA.
EM adas@unm.edu
FU NEI NIH HHS [R01 EY12604-05] Funding Source: Medline; NATIONAL EYE
   INSTITUTE [R01EY012604] Funding Source: NIH RePORTER
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NR 223
TC 180
Z9 194
U1 0
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 NOV
PY 2003
VL 22
IS 6
BP 721
EP 748
DI 10.1016/j.preteyeres.2003.08.001
PG 28
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 738HJ
UT WOS:000186280900002
PM 14575722
DA 2022-11-30
ER

PT J
AU Gonzalez-Zamora, J
   Hernandez, M
   Recalde, S
   Bezunartea, J
   Montoliu, A
   Bilbao-Malave, V
   Orbe, J
   Rodriguez, JA
   Llorente-Gonzalez, S
   Fernandez-Robredo, P
   Garcia-Layana, A
AF Gonzalez-Zamora, Jorge
   Hernandez, Maria
   Recalde, Sergio
   Bezunartea, Jaione
   Montoliu, Ana
   Bilbao-Malave, Valentina
   Orbe, Josune
   Rodriguez, Jose A.
   Llorente-Gonzalez, Sara
   Fernandez-Robredo, Patricia
   Garcia-Layana, Alfredo
TI Matrix Metalloproteinase 10 Contributes to Choroidal Neovascularisation
SO BIOMEDICINES
LA English
DT Article
DE matrix metalloproteinase; age-related macular degeneration; oxidative
   stress; choroidal neovascularisation; angiogenesis
ID MICROVASCULAR COMPLICATIONS; MACULAR DEGENERATION; SERUM-LEVELS;
   INFLAMMATION; EXPRESSION; MMP-10
AB Age-related macular degeneration (AMD) is currently the main cause of severe visual loss among older adults in developed countries. The pathophysiology has not been clarified, but oxidative stress is believed to play a major role. Matrix metalloproteinases (MMP) may play a prominent role in several steps of the pathophysiology of AMD, especially in its neovascular form; therefore, there is of great interest in understanding their role in choroidal neovascularisation. This study aimed to elucidate the role of MMP10 in the development of choroidal neovascularisation (CNV). We have demonstrated that MMP10 was expressed by retinal pigment epithelium cells and endothelial cells of the neovascular membrane, in cell culture, mouse and human retina. MMP10 expression and activity increased under oxidative stress conditions in ARPE-19 cells. MMP10(-/-) mice developed smaller laser-induced areas of CNV. Furthermore, to exclude a systemic MMP10 imbalance in these patients, plasma MMP10 concentrations were assessed in an age- and sex-matched sample of 52 control patients and 52 patients with neovascular AMD and no significant differences were found between the groups, demonstrating that MMP10 induction is a local phenomenon. Our findings suggest that MMP10 participates in the development of choroidal neovascularisation and promotes MMP10 as a possible new therapeutic target.
C1 [Gonzalez-Zamora, Jorge; Hernandez, Maria; Recalde, Sergio; Bezunartea, Jaione; Montoliu, Ana; Bilbao-Malave, Valentina; Llorente-Gonzalez, Sara; Fernandez-Robredo, Patricia; Garcia-Layana, Alfredo] Clin Univ Navarra, Dept Ophthalmol, Expt Ophthalmol Lab, Retinal Pathol & New Therapies Grp, Pamplona 31008, Spain.
   [Hernandez, Maria; Recalde, Sergio; Bezunartea, Jaione; Orbe, Josune; Rodriguez, Jose A.; Llorente-Gonzalez, Sara; Fernandez-Robredo, Patricia; Garcia-Layana, Alfredo] IdiSNA, Navarra Inst Hlth Res, Pamplona 31008, Spain.
   [Orbe, Josune; Rodriguez, Jose A.] CIMA Univ Navarra, Lab Atherothrombosis, CIBERCV, Program Cardiovasc Dis, Pamplona 31008, Spain.
C3 University of Navarra; CIBER - Centro de Investigacion Biomedica en Red;
   CIBERCV; University of Navarra
RP Hernandez, M; Fernandez-Robredo, P (通讯作者)，Clin Univ Navarra, Dept Ophthalmol, Expt Ophthalmol Lab, Retinal Pathol & New Therapies Grp, Pamplona 31008, Spain.; Hernandez, M; Fernandez-Robredo, P (通讯作者)，IdiSNA, Navarra Inst Hlth Res, Pamplona 31008, Spain.
EM jgzamora@unav.es; mahersan@unav.es; srecalde@unav.es;
   jbezunartea@unav.es; amontoliu@unav.es; vbilbao@unav.es;
   josuneor@unav.es; josean@unav.es; sllorente@unav.es; pfrobredo@unav.es;
   aglayana@unav.es
RI Recalde, Sergio/D-1815-2017; Orbe, Josune/D-3082-2017; Rodriguez,
   Jose/G-7324-2015
OI Recalde, Sergio/0000-0002-9328-9725; Orbe, Josune/0000-0001-6300-7670;
   Rodriguez, Jose/0000-0002-2094-264X; LLORENTE GONZALEZ,
   SARA/0000-0001-8815-4757
FU Thea Laboratoires; Fundacion Jesus Gangoiti Barrera; Multiopticas (CUN
   2019); Red Tematica de Investigacion Cooperativa en Salud: 'Prevention,
   Early Detection and Treatment of the Prevalent Degenerative and Chronic
   Ocular Pathology' [RD16/0008/0011]; Redes de Investigacion Cooperativa
   Orientadas al Resultado en Salud (RICORS) de Terapias avanzadas
   [RD21/0017/0027]; Enfermedades Inflamatorias [RD21/0002/0010];
   Enfermedades vasculares cerebrales, Ministerio de Ciencia, Innovacion y
   Universidades, Instituto de Salud Carlos III, Madrid, Spain
   [RD21/0006/0008]
FX The present work was partially funded by Thea Laboratoires (01/2019),
   Fundacion Jesus Gangoiti Barrera (2020-2021) and a collaborative project
   with Multiopticas (CUN 2019). Moreover, the work was partially supported
   by Red Tematica de Investigacion Cooperativa en Salud: `Prevention,
   Early Detection and Treatment of the Prevalent Degenerative and Chronic
   Ocular Pathology' (RD16/0008/0011), Redes de Investigacion Cooperativa
   Orientadas al Resultado en Salud (RICORS) de Terapias avanzadas
   (RD21/0017/0027), Enfermedades Inflamatorias (RD21/0002/0010) y
   Enfermedades vasculares cerebrales (RD21/0006/0008), Ministerio de
   Ciencia, Innovacion y Universidades, Instituto de Salud Carlos III,
   28029 Madrid, Spain.
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NR 49
TC 0
Z9 0
U1 0
U2 0
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2227-9059
J9 BIOMEDICINES
JI Biomedicines
PD JUL
PY 2022
VL 10
IS 7
AR 1557
DI 10.3390/biomedicines10071557
PG 16
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental;
   Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Research & Experimental Medicine;
   Pharmacology & Pharmacy
GA 3J2EX
UT WOS:000833214800001
PM 35884862
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Ahmad, A
   Mandwie, M
   Dreismann, AK
   Smyth, CM
   Doyle, H
   Malik, TH
   Pickering, MC
   Lachmann, PJ
   Alexander, IE
   Logan, GJ
AF Ahmad, Amina
   Mandwie, Mawj
   Dreismann, Anna K.
   Smyth, Christine M.
   Doyle, Helen
   Malik, Talat H.
   Pickering, Matthew C.
   Lachmann, Peter J.
   Alexander, Ian E.
   Logan, Grant J.
TI Adeno-Associated Virus Vector Gene Delivery Elevates Factor I Levels and
   Downregulates the Complement Alternative Pathway In Vivo
SO HUMAN GENE THERAPY
LA English
DT Article
DE adeno-associated virus; complement; factor I; alternative pathway;
   immune modulation
ID FACTOR-B; COMPONENT; THERAPY; CELLS; SERUM; C3; GLOMERULONEPHRITIS;
   TRANSDUCTION; INFLAMMATION; EXPRESSION
AB The complement system is a key component of innate immunity, but impaired regulation influences disease susceptibility, including age-related macular degeneration and some kidney diseases. While complete complement inhibition has been used successfully to treat acute kidney disease, key unresolved challenges include strategies to modulate rather than completely inhibit the system and to deliver therapy potentially over decades. Elevating concentrations of complement factor I (CFI) restricts complement activation in vitro and this approach was extended in the current study to modulate complement activation in vivo. Sustained increases in CFI levels were achieved using an adeno-associated virus (AAV) vector to target the liver, inducing a 4- to 5-fold increase in circulating CFI levels. This led to decreased activity of the alternative pathway as demonstrated by a reduction in the rate of inactive C3b (iC3b) deposition and more rapid formation of C3 degradation products. In addition, vector application in a mouse model of systemic lupus erythematosus (NZBWF1), where tissue injury is, in part, complement dependent, resulted in reduced complement C3 and IgG renal deposition. Collectively, these data demonstrate that sustained elevation of CFI reduces complement activation in vivo providing proof-of-principle support for the therapeutic application of AAV gene delivery to modulate complement activation.
C1 [Ahmad, Amina; Mandwie, Mawj; Smyth, Christine M.; Alexander, Ian E.; Logan, Grant J.] Univ Sydney, Childrens Med Res Inst, Gene Therapy Res Unit, Westmead, NSW, Australia.
   [Ahmad, Amina; Mandwie, Mawj; Smyth, Christine M.; Alexander, Ian E.; Logan, Grant J.] Univ Sydney, Sydney Childrens Hosp Network, Westmead, NSW, Australia.
   [Dreismann, Anna K.; Lachmann, Peter J.] Univ Cambridge, Dept Vet Med, Cambridge, England.
   [Doyle, Helen] Sydney Childrens Hosp Network, Pathol, Westmead, NSW, Australia.
   [Malik, Talat H.; Pickering, Matthew C.] Imperial Coll London, Ctr Inflammatory Dis, London, England.
   [Alexander, Ian E.] Univ Sydney, Discipline Child & Adolescent Hlth, Westmead, NSW, Australia.
C3 Children's Medical Research Institute - Australia; University of Sydney;
   University of Sydney; University of Cambridge; Imperial College London;
   University of Sydney
RP Logan, GJ (通讯作者)，Univ Sydney, Childrens Med Res Inst, Gene Therapy Res Unit, Westmead, NSW, Australia.; Logan, GJ (通讯作者)，Univ Sydney, Sydney Childrens Hosp Network, Westmead, NSW, Australia.
EM glogan@cmri.org.au
OI /0000-0001-9365-342X; Mandwie, Mawj/0000-0002-4165-4276
FU Rebecca L Cooper Foundation [PG2019449]
FX G.J.L. received funding support from the Rebecca L Cooper Foundation
   (PG2019449).
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NR 45
TC 5
Z9 5
U1 2
U2 6
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 NOV 1
PY 2021
VL 32
IS 21-22
BP 1370
EP 1381
DI 10.1089/hum.2021.022
EA AUG 2021
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA WZ1UZ
UT WOS:000689738500001
PM 34238030
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Khanani, AM
   Aziz, AA
   Weng, CY
   Lin, WV
   Vannavong, J
   Chhablani, J
   Danzig, CJ
   Kaiser, PK
AF Khanani, Arshad M.
   Aziz, Aamir A.
   Weng, Christina Y.
   Lin, Weijie Violet
   Vannavong, Jordyn
   Chhablani, Jay
   Danzig, Carl J.
   Kaiser, Peter K.
TI Port delivery system: a novel drug delivery platform to treat retinal
   diseases
SO EXPERT OPINION ON DRUG DELIVERY
LA English
DT Article
DE Age-related macular degeneration; anti-vegf; intravitreal injection;
   macular edema; neovascular; portal delivery system; ranibizumab
AB Introduction Retinal disease treatment delivery is mostly limited to intravitreal injections and slow-release injectable implants due to structural barriers in the eye, and carry associated adverse effects and relatively high treatment burden. The Port Delivery System with ranibizumab (PDS) is a novel drug delivery device that is surgically implanted into the vitreous cavity and allows for continuous release of the anti-vascular endothelial growth factor (anti-VEGF) ranibizumab, eliminating the need for frequent intravitreal injections while maintaining therapeutic intraocular drug levels to control disease activity. Investigations of PDS are summarized in this review. Areas covered The most recent reported findings from preliminary studies and phase I-III trials are reviewed. We discuss the ramifications of these studies and the future potential for PDS in the treatment of retinal diseases. Expert opinion PDS is a novel drug delivery platform for the treatment of retinal diseases. Currently, the data from the PDS has shown promising efficacy and ability to substantially mitigate treatment burden while effectively generating visual and anatomic outcomes similar to those in patients receiving the standard monthly ranibizumab for neovascular age-related macular degeneration. Further studies are ongoing to investigate this novel drug delivery system in other disease states.
C1 [Khanani, Arshad M.; Aziz, Aamir A.; Vannavong, Jordyn] Sierra Eye Associates, Reno, NV USA.
   [Khanani, Arshad M.; Aziz, Aamir A.] Univ Nevada, Reno Sch Med, 950 Ryland St, Reno, NV 89502 USA.
   [Weng, Christina Y.] Baylor Coll Med, Cullen Eye Inst, Dept Ophthalmol, Houston, TX 77030 USA.
   [Lin, Weijie Violet] Columbia Univ, Dept Ophthalmol, Harkness Eye Inst, Med Ctr, New York, NY 10027 USA.
   [Chhablani, Jay] Univ Pittsburgh, Dept Ophthalmol, UPMC Eye Ctr, Med Ctr, Pittsburgh, PA 15260 USA.
   [Danzig, Carl J.] Rand Eye Inst, Deerfield Beach, FL USA.
   [Danzig, Carl J.] Florida Atlantic Univ, Boca Raton, FL 33431 USA.
   [Kaiser, Peter K.] Cleveland Clin, Cole Eye Inst, Cleveland, OH 44106 USA.
C3 Nevada System of Higher Education (NSHE); University of Nevada Reno;
   Baylor College of Medicine; Columbia University; Pennsylvania
   Commonwealth System of Higher Education (PCSHE); University of
   Pittsburgh; State University System of Florida; Florida Atlantic
   University; Cleveland Clinic Foundation
RP Khanani, AM (通讯作者)，Univ Nevada, Reno Sch Med, 950 Ryland St, Reno, NV 89502 USA.
EM arshad.khanani@gmail.com
OI Khanani, Arshad/0000-0001-8928-5599; Aziz, Aamir/0000-0002-3657-4861;
   Lin, Weijie/0000-0002-1894-4267
CR [Anonymous], 2020, ROCH PORT DEL SYST R
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NR 30
TC 10
Z9 11
U1 3
U2 5
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1742-5247
EI 1744-7593
J9 EXPERT OPIN DRUG DEL
JI Expert Opin. Drug Deliv.
PD NOV 2
PY 2021
VL 18
IS 11
BP 1571
EP 1576
DI 10.1080/17425247.2021.1968826
EA AUG 2021
PG 6
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA WQ4YT
UT WOS:000687955600001
PM 34388956
DA 2022-11-30
ER

PT J
AU Yasuda, H
   Tanaka, M
   Nishinaka, A
   Nakamura, S
   Shimazawa, M
   Hara, H
AF Yasuda, Hiroto
   Tanaka, Miruto
   Nishinaka, Anri
   Nakamura, Shinsuke
   Shimazawa, Masamitsu
   Hara, Hideaki
TI Role of Activating Transcription Factor 4 in Murine Choroidal
   Neovascularization Model
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE activating transcription factor 4; neovascular age-related macular
   degeneration; choroidal neovascularization; integrated stress response;
   ISRIB; vascular endothelial growth factor; autocrine; endothelial cell
ID UNFOLDED PROTEIN RESPONSE; ENDOTHELIAL GROWTH-FACTOR; MACULAR
   DEGENERATION; VEGF EXPRESSION; ANTI-VEGF; IN-VITRO; ANGIOGENESIS;
   STRESS; CELLS; ATF4
AB Neovascular age-related macular degeneration (nAMD) featuring choroidal neovascularization (CNV) is the principal cause of irreversible blindness in elderly people in the world. Integrated stress response (ISR) is one of the intracellular signals to be adapted to various stress conditions including endoplasmic reticulum (ER) stress. ISR signaling results in the upregulation of activating transcription factor 4 (ATF4), which is a mediator of ISR. Although recent studies have suggested ISR contributes to the progression of some age-related disorders, the effects of ATF4 on the development of CNV remain unclear. Here, we performed a murine model of laser-induced CNV and found that ATF4 was highly expressed in endothelial cells of the blood vessels of the CNV lesion site. Exposure to integrated stress inhibitor (ISRIB) reduced CNV formation, vascular leakage, and the upregulation of vascular endothelial growth factor (VEGF) in retinal pigment epithelium (RPE)-choroid-sclera complex. In human retinal microvascular endothelial cells (HRMECs), ISRIB reduced the level of ATF4 and VEGF induced by an ER stress inducer, thapsigargin, and recombinant human VEGF. Moreover, ISRIB decreased the VEGF-induced cell proliferation and migration of HRMECs. Collectively, our findings showed that pro-angiogenic effects of ATF4 in endothelial cells may be a potentially therapeutic target for patients with nAMD.
C1 [Yasuda, Hiroto; Tanaka, Miruto; Nishinaka, Anri; Nakamura, Shinsuke; Shimazawa, Masamitsu; Hara, Hideaki] Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Gifu 5011196, Japan.
C3 Gifu Pharmaceutical University
RP Hara, H (通讯作者)，Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Gifu 5011196, Japan.
EM yasuda.yakkou@gmail.com; tanakamiruto.yakkou@gmail.com;
   nishinaka.yakkou@gmail.com; nakamuras@gifu-pu.ac.jp;
   shimazawa@gifu-pu.ac.jp; hidehara@gifu-pu.ac.jp
OI Hara, Hideaki/0000-0003-2046-9001
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NR 53
TC 0
Z9 0
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 AUG
PY 2021
VL 22
IS 16
AR 8890
DI 10.3390/ijms22168890
PG 14
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA UG2UD
UT WOS:000689113200001
PM 34445595
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Sauer, L
   Vitale, AS
   Modersitzki, NK
   Bernstein, PS
AF Sauer, Lydia
   Vitale, Alexandra S.
   Modersitzki, Natalie K.
   Bernstein, Paul S.
TI Fluorescence lifetime imaging ophthalmoscopy: autofluorescence imaging
   and beyond
SO EYE
LA English
DT Review
ID PIGMENT EPITHELIAL DETACHMENTS; TIME-RESOLVED AUTOFLUORESCENCE; FUNDUS
   AUTOFLUORESCENCE; MACULAR DEGENERATION; HYDROXYCHLOROQUINE RETINOPATHY;
   DIABETIC-RETINOPATHY; LIPOFUSCIN; CLASSIFICATION; PATHOGENESIS;
   PREVALENCE
AB Fluorescence lifetime imaging ophthalmoscopy, FLIO, has gained large interest in the scientific community in the recent years. It is a noninvasive imaging modality that has been shown to provide additional information to conventional imaging modalities. The FLIO device is based on a Heidelberg Engineering Spectralis system. Autofluorescence lifetimes are excited at 473 nm and recorded in two spectral wavelength channels, a short spectral channel (SSC, 498-560 nm) and a long spectral channel (LSC, 560-720 nm). Typically, mean autofluorescence lifetimes in a 30 degrees retinal field are investigated. FLIO shows a clear benefit for imaging different retinal diseases. For example, in age-related macular degeneration (AMD), ring patterns of prolonged FLIO lifetimes 1.5-3.0 mm from the fovea can be appreciated. Macular telangiectasia type 2 (MacTel) shows a different pattern, with prolonged FLIO lifetimes within the typical MacTel zone. In Stargardt disease, retinal flecks can be appreciated even before they are visible with other imaging modalities. Early hydroxychloroquine toxicity appears to be detectable with FLIO. This technique has more potential that has yet to be discovered. This review article focuses on current knowledge as well as pitfalls of this technology. It highlights clinical benefits of FLIO imaging in different ophthalmic and systemic diseases, and provides an outlook with perspectives from the authors.
C1 [Sauer, Lydia; Vitale, Alexandra S.; Modersitzki, Natalie K.; Bernstein, Paul S.] Univ Utah, Sch Med, Moran Eye Ctr, Dept Ophthalmol & Visual Sci, 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, Sch Med, Moran Eye Ctr, Dept Ophthalmol & Visual Sci, 65 Mario Capecchi Dr, Salt Lake City, UT 84132 USA.
EM paul.bernstein@hsc.utah.edu
OI Bernstein, Paul/0000-0002-4228-7666
FU NIH [EY11600, EY14800]; Lowy Medical Research Institute, Research to
   Prevent Blindness
FX NIH grants EY11600 and EY14800; Lowy Medical Research Institute,
   Research to Prevent Blindness.
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NR 87
TC 14
Z9 14
U1 1
U2 4
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD JAN
PY 2021
VL 35
IS 1
BP 93
EP 109
DI 10.1038/s41433-020-01287-y
EA DEC 2020
PG 17
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA PI7BU
UT WOS:000595392100001
PM 33268846
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Ferroni, M
   De Gaetano, F
   Cereda, MG
   Boschetti, F
AF Ferroni, Marco
   De Gaetano, Francesco
   Cereda, Matteo Giuseppe
   Boschetti, Federica
TI Evaluation of the ocular fluid dynamic effects on intraocular
   magnesium-based device: A comparison between CFD and FSI approaches
SO MEDICAL ENGINEERING & PHYSICS
LA English
DT Article
DE Drug delivery; Magnesium; Computational fluid dynamics; Fluid-structure
   interaction; Numerical modelling
ID ENDOTHELIAL GROWTH-FACTOR; DRUG-DELIVERY; CORROSION BEHAVIOR;
   CORONARY-ARTERY; EYE; DEGRADATION; ALLOY; FLOW; MG; MOVEMENTS
AB Magnesium is an essential element for the ocular functions and used for the realization of medical devices due to its low corrosion resistance, bioresorbable nature and biocompatibility. Wet age-related macular degeneration is one of the main causes of blindness with patients treated by intravitreal injections of inhibitor drugs. According to the need to reduce the number of injections, the development of new drug delivery devices able to extend the therapeutical outcomes is mandatory and magnesium can be considered as a promising candidate. The aim of the work concerns the evaluation of the ocular fluid dynamic role on a magnesium-based device placed in the vitreous chamber. Particularly, the fluid-induced shear stress field on the surfaces in contact with the liquefied vitreous was studied. Both computational fluid dynamic and fluid-structure interaction approaches were proposed and then compared. Saccadic motion was implemented to recreate the vitreous fluid dynamics. High changes in terms of fluid-induced shear stress field varying the CFD and FSI numerical approaches and kinematic parameters of the saccadic function can be noticed. The comparison between CFD and FSI approaches showed minor significant differences and both implementations suggested the possibility to obtain a uniform and controlled corrosion of the device. (c) 2020 IPEM. Published by Elsevier Ltd. All rights reserved.
C1 [Ferroni, Marco; De Gaetano, Francesco; Boschetti, Federica] Politecn Milan, Chem Mat & Chem Engn Dept Giulio Natta, LaBS, Piazza L da Vinci 32, I-20133 Milan, Italy.
   [Cereda, Matteo Giuseppe] Univ Milan, Sacco Hosp, Dept Biomed & Clin Sci Luigi Sacco, Eye Clin, Via GB Grassi 74, I-20157 Milan, Italy.
   [Ferroni, Marco; De Gaetano, Francesco] MgShell Srl, Milan, Italy.
C3 Polytechnic University of Milan; University of Milan; Luigi Sacco
   Hospital
RP Ferroni, M (通讯作者)，Politecn Milan, Chem Mat & Chem Engn Dept Giulio Natta, LaBS, Piazza L da Vinci 32, I-20133 Milan, Italy.
EM marco.ferroni@polimi.it
FU Italian Ophthalmological Society (SOI)
FX This study was funded by the Italian Ophthalmological Society (SOI).
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NR 56
TC 0
Z9 0
U1 1
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1350-4533
EI 1873-4030
J9 MED ENG PHYS
JI Med. Eng. Phys.
PD DEC
PY 2020
VL 86
BP 20
EP 28
DI 10.1016/j.medengphy.2020.10.004
PG 9
WC Engineering, Biomedical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering
GA PA4KC
UT WOS:000595605800004
PM 33261729
DA 2022-11-30
ER

PT J
AU Usategui-Martin, R
   Puertas-Neyra, K
   Garcia-Gutierrez, MT
   Fuentes, M
   Pastor, JC
   Fernandez-Bueno, I
AF Usategui-Martin, Ricardo
   Puertas-Neyra, Kevin
   Garcia-Gutierrez, Maria-Teresa
   Fuentes, Manuel
   Carlos Pastor, Jose
   Fernandez-Bueno, Ivan
TI Human Mesenchymal Stem Cell Secretome Exhibits a Neuroprotective Effect
   over In Vitro Retinal Photoreceptor Degeneration
SO MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
LA English
DT Article
ID KNEE OSTEOARTHRITIS; SIGNALING PATHWAYS; DIFFERENTIATION;
   TRANSPLANTATION; IDENTIFICATION; INTEGRATE; CULTURE; REPAIR; MODEL
AB Retinal photoreceptor degeneration occurs frequently in several neurodegenerative retinal diseases such as age-related macular degeneration, retinitis pigmentosa, or genetic retinal diseases related to the photoreceptors. Despite the impact on daily life and the social and economic consequences, there is no cure for these diseases. Considering this, cell-based therapy may be an optimal therapeutic option. This study evaluated the neuroprotective in vitro potential of a secretome of human bone marrow mesenchymal stem cells (MSCs) for retinal photoreceptors in vitro. We analyzed the photoreceptor morphologic changes and the paracrine factors secreted by human bone marrow MSCs in a physically separated co-culture with degenerated neuroretinas, using organotypic neuroretinal cultures. The results showed that the secretome of human bone marrow MSCs had a neuroprotective effect over the neuroretinal general organization and neuropreserved the photoreceptors from degeneration probably by secretion of neuroprotective proteins. The study of the expression of 1,000 proteins showed increased paracrine factors secreted by MSCs that could be crucial in the neuroprotective effect of the stem cell secretome over in vitro retinal degeneration. The current results reinforce the hypothesis that the paracrine effect of the human bone marrow MSCs may slow photoreceptor neurodegeneration and be a therapeutic option in retinal photoreceptor degenerative diseases.
C1 [Usategui-Martin, Ricardo; Puertas-Neyra, Kevin; Garcia-Gutierrez, Maria-Teresa; Carlos Pastor, Jose; Fernandez-Bueno, Ivan] Univ Valladolid, Retina Grp, Inst Univ Oftalmobiol Aplicada IOBA, Campus Miguel Delibes,Paseo Belen 17, Valladolid 47011, Spain.
   [Fuentes, Manuel] Univ Salamanca, Inst Biomed Res Salamanca IBSAL, Prote Unit, Canc Res Ctr IBMCC CSIC, Salamanca 37007, Spain.
   [Fuentes, Manuel] Univ Salamanca, Inst Biomed Res Salamanca IBSAL, Dept Med & Gen Cytometry Serv Nucleus, CIBERONC CB16 12 00400,Canc Res Ctr IBMCC CSIC, Salamanca 37007, Spain.
   [Carlos Pastor, Jose] Hosp Clin Univ Valladolid, Dept Ophthalmol, Valladolid 47003, Spain.
   [Carlos Pastor, Jose; Fernandez-Bueno, Ivan] Ctr Red Med Regenerat & Terapia Celular Castilla, Valladolid 47011, Spain.
   [Carlos Pastor, Jose; Fernandez-Bueno, Ivan] Inst Salud Carlos III, Red Temat Invest Cooperat Salud RETICS, Oftared, Valladolid 47011, Spain.
C3 Universidad de Valladolid; Consejo Superior de Investigaciones
   Cientificas (CSIC); CSIC-USAL - Instituto de Biologia Molecular y
   Celular del Cancer de Salamanca (IBMCC); University of Salamanca;
   Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-USAL -
   Instituto de Biologia Molecular y Celular del Cancer de Salamanca
   (IBMCC); University of Salamanca; Instituto de Salud Carlos III
RP Fernandez-Bueno, I (通讯作者)，Univ Valladolid, Retina Grp, Inst Univ Oftalmobiol Aplicada IOBA, Campus Miguel Delibes,Paseo Belen 17, Valladolid 47011, Spain.
EM ifernandezb@ioba.med.uva.es
RI Neyra, Kevin Louis Puertas/AAS-3495-2021
OI Puertas Neyra, Kevin Louis/0000-0002-9641-4042
FU Fondo Europeo de Desarrollo Regional (FEDER); Consejeria de Educacion
   from Junta de Castilla y Leon, Spain [VA077P17]; Spanish Health
   Institute Carlos III (ISCIII) [PI17/01930, CB16/12/00400]; PEI+D+I
   2017-2020 - ISCIII [PT17/0019/0023]; FEDER; Fundacion Carolina, Madrid,
   Spain; Centro en Red de Medicina Regenerativa y Terapia Celular, Junta
   de Castilla y Leon, Spain
FX The authors are grateful to the staff of the Justino Gutierrez S.L.
   Slaughterhouse (Valladolid, Spain) for providing the porcine eye globes
   used in this work and to Citospin S.L. (Valladolid, Spain) for providing
   the MSCs used in this work. We also thank Lynda Charters from Medical
   International (Framingham, MA, USA) for his assistance in the final
   editing and preparation of this manuscript. This work was supported by
   grants from Fondo Europeo de Desarrollo Regional (FEDER) and Consejeria
   de Educacion from Junta de Castilla y Leon, Spain (grant VA077P17), and
   from the Spanish Health Institute Carlos III (ISCIII) (grants PI17/01930
   and CB16/12/00400). The Proteomics Unit belongs to ProteoRed
   (PRB3-ISCIII) supported by grant PT17/0019/0023, of the PEI+D+I
   2017-2020, funded by ISCIII and FEDER. R.U.-M. was supported by FEDER
   and Consejeria de Educacion from Junta de Castilla y Leon, Spain (grant
   VA077P17); K.P.-N. was supported by Fundacion Carolina, Madrid, Spain;
   and I.F.-B. was supported by Centro en Red de Medicina Regenerativa y
   Terapia Celular, Junta de Castilla y Leon, Spain.
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NR 48
TC 13
Z9 13
U1 1
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
EI 2329-0501
J9 MOL THER-METH CLIN D
JI Mol.Ther.-Methods Clin. Dev.
PD JUN 12
PY 2020
VL 17
BP 1155
EP 1166
DI 10.1016/j.omtm.2020.05.003
PG 12
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA LZ0FC
UT WOS:000540906400103
PM 32514411
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Erdogan, G
   Kirmaci, A
   Perente, I
   Artunay, O
AF Erdogan, Gurkan
   Kirmaci, Asli
   Perente, Irfan
   Artunay, Ozgur
TI Gravitational displacement of submacular haemorrhage in patients with
   age-related macular disease
SO EYE
LA English
DT Article
ID TISSUE-PLASMINOGEN-ACTIVATOR; PNEUMATIC DISPLACEMENT; SUBRETINAL
   HEMORRHAGE; VITRECTOMY; INJECTION; GAS
AB Objectives To investigate the efficacy of gravitational displacement following vitrectomy for the patients with submacular haemorrhage (SMH) secondary to age-related macular degeneration (AMD). Methods Retrospective, interventional series of nine consecutive AMD patients with SMH. All patients underwent pars plana vitrectomy (PPV) combined with subretinal tissue plasminogen activator (t-PA) and intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection without any tamponade. The patients were positioned according to the location and distribution of SMH postoperatively in order to provide the maximum gravitational force effect to displace. Outcome measures were the change in visual acuity, the displacement in SMH, and the occurrence of per- and postoperative complications. Results Complete displacement of haemorrhage occurred in all patients postoperatively. The mean preoperative and postoperative best-corrected visual acuity (BCVA) at the last visit were 2.46 and 1.7 logMAR, respectively, after a mean follow-up of 10.4 months (Range: 3-18 months) (p = 0.045). The mean duration of haemorrhage was 15.3 days (range: 3-40 days). The recurrence of SMH was observed in two (22%) patients and there were no other postoperative complications. Conclusion Gravitational displacement following PPV combined with subretinal t-PA and intravitreal anti-VEGF injection can be considered as an effective surgical intervention in selected AMD patients with SMH.
C1 [Erdogan, Gurkan; Kirmaci, Asli; Perente, Irfan; Artunay, Ozgur] Univ Hlth Sci, Beyoglu Eye Training & Res Hosp, Istanbul, Turkey.
C3 University of Health Sciences Turkey
RP Erdogan, G (通讯作者)，Univ Hlth Sci, Beyoglu Eye Training & Res Hosp, Istanbul, Turkey.
EM erdogangurkan@yahoo.com
RI Erdogan, Gurkan/AAV-3972-2021; Kabakci, Asli Kirmaci/AAN-2690-2020
OI Erdogan, Gurkan/0000-0003-4155-0407; Kabakci, Asli
   Kirmaci/0000-0003-4032-4467
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NR 15
TC 2
Z9 2
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 2020
VL 34
IS 6
BP 1136
EP 1141
DI 10.1038/s41433-019-0720-8
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA LR9NJ
UT WOS:000536021600024
PM 31792350
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Stromer, D
   Moult, EM
   Chen, SY
   Waheed, NK
   Maier, A
   Fujimoto, JG
AF Stromer, Daniel
   Moult, Eric M.
   Chen, Siyu
   Waheed, Nadia K.
   Maier, Andreas
   Fujimoto, James G.
TI Correction propagation for user-assisted optical coherence tomography
   segmentation: general framework and application to Bruch's membrane
   segmentation
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID RETINAL LAYER SEGMENTATION; SD-OCT IMAGES; AUTOMATIC SEGMENTATION;
   SURFACE SEGMENTATION; GEOGRAPHIC ATROPHY; MOTION CORRECTION;
   NEOVASCULARIZATION; CHORIOCAPILLARIS; ANGIOGRAPHY; MODEL
AB Optical coherence tomography (OCT) is a commonly used ophthalmic imaging modality. While OCT has traditionally been viewed cross-sectionally (i.e., as a sequence of B-scans), higher A-scan rates have increased interest in en face OCT visualization and analysis. The recent clinical introduction of OCT angiography (OCTA) has further spurred this interest, with chorioretinal OCTA being predominantly displayed via en face projections. Although en face visualization and quantitation are natural for many retinal features (e.g., drusen and vasculature), it requires segmentation. Because manual segmentation of volumetric OCT data is prohibitively laborious in many settings, there has been significant research and commercial interest in developing automatic segmentation algorithms. While these algorithms have achieved impressive results, the variability of image qualities and the variety of ocular pathologies cause even the most robust automatic segmentation algorithms to err. In this study, we develop a user-assisted segmentation approach, complementary to fully-automatic methods, wherein correction propagation is used to reduce the burden of manually correcting automatic segmentations. The approach is evaluated for Bruch's membrane segmentation in eyes with advanced age-related macular degeneration. (C) 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
C1 [Stromer, Daniel; Moult, Eric M.; Chen, Siyu; Fujimoto, James G.] MIT, Dept Elect Engn & Comp Sci, Res Lab Elect, Cambridge, MA 02139 USA.
   [Stromer, Daniel; Maier, Andreas] Friedrich Alexander Univ Erlangen Nurnberg, Pattern Recognit Lab, Erlangen, Germany.
   [Waheed, Nadia K.] Tufts Med Ctr, New England Eye Ctr, Boston, MA 02111 USA.
C3 Massachusetts Institute of Technology (MIT); University of Erlangen
   Nuremberg; Tufts Medical Center
RP Fujimoto, JG (通讯作者)，MIT, Dept Elect Engn & Comp Sci, Res Lab Elect, Cambridge, MA 02139 USA.
EM jgfuji@mit.edu
RI CHEN, SI/GZL-4800-2022; Maier, Andreas/AAV-6505-2021
OI Maier, Andreas/0000-0002-9550-5284
FU National Eye Institute [R01-EY011289]; Research to Prevent Blindness;
   Champalimaud Vision Award; Beckman-Argyros Award in VisionResearch;
   Retina Research Foundation Awards
FX National Eye Institute (R01-EY011289); Research to Prevent Blindness;
   Champalimaud Vision Award; Beckman-Argyros Award in VisionResearch;
   Retina Research Foundation Awards.
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NR 33
TC 2
Z9 2
U1 0
U2 1
PU Optica Publishing Group
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 2156-7085
J9 BIOMED OPT EXPRESS
JI Biomed. Opt. Express
PD MAY 1
PY 2020
VL 11
IS 5
BP 2830
EP 2848
DI 10.1364/BOE.392759
PG 19
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 LM9KW
UT WOS:000532568000040
PM 32499964
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Biswas, L
   Zeng, ZH
   Graham, A
   Shu, XH
AF Biswas, Lincoln
   Zeng, Zhihong
   Graham, Annette
   Shu, Xinhua
TI Gypenosides mediate cholesterol efflux and suppress oxidized LDL induced
   inflammation in retinal pigment epithelium cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Gypenosides; Cholesterol efflux; Oxidized LDL; Inflammation; Retinal
   pigment epithelium
ID KDA TRANSLOCATOR PROTEIN; FATTY LIVER-DISEASE; OXIDATIVE STRESS; X
   RECEPTOR; LXR-ALPHA; DENSITY; DEGENERATION; MECHANISMS; LIPOPROTEINS;
   ASSOCIATION
AB Age-related macular degeneration (AMD) is a predominant cause of visual deficit in aged population. Abnormal accumulation of cholesterol, including oxidized low-density lipoprotein (oxLDL), underneath the retinal pigment epithelium (RPE) cells contributes to the development of AMD. Gypenosides (Gyp) are glycosides extracted from Gynostemma pentaphyllum and have demonstrated protective effects against inflammation and oxidative stress. To determine the therapeutic potential of Gyp for AMD, we investigated its effect on cholesterol trafficking and metabolism and assessed the protective function of Gyp against oxLDL-induced damage in RPE cells. Cholesterol efflux to high-density lipoprotein (HDL) and human serum was significantly increased in RPE cells treated with Gyp when compared to untreated control cells. Expression of cholesterol metabolism (CYP27A1, CYP46A1) and trafficking (TSPO, ABCA1 and ABCG1) genes was also markedly increased in Gyp-treated RPE cells. OxLDL-treated RPE cells had significantly increased cholesterol accumulation and lipid droplet formation. There were marked increases in reactive oxygen species (ROS) generation and proinflammatory cytokines via NF-kappa B activation in RPE cells treated with oxLDL, while incubation with Gyp rectified these changes. These findings provide pharmacological evidence that Gyp has the potential to treat patients with early onset AMD by promoting cellular cholesterol removal from RPE cells and inhibiting inflammation and oxidative stress.
C1 [Biswas, Lincoln; Graham, Annette; Shu, Xinhua] Glasgow Caledonian Univ, Dept Biol & Biomed Sci, Glasgow G4 0BA, Lanark, Scotland.
   [Zeng, Zhihong] Changsha Univ, Coll Biol & Environm Engn, Changsha 410022, Hunan, Peoples R China.
   [Shu, Xinhua] Glasgow Caledonian Univ, Dept Vis Sci, Glasgow G4 0BA, Lanark, Scotland.
C3 Glasgow Caledonian University; Changsha University; Glasgow Caledonian
   University
RP Shu, XH (通讯作者)，Glasgow Caledonian Univ, Dept Biol & Biomed Sci, Glasgow G4 0BA, Lanark, Scotland.
EM Xinhua.Shu@gcu.ac.uk
RI Zeng, Zhihong/HEV-8703-2022
FU Rosetrees Trust [M160, M160-F1, M160-F2]; National Eye Research Centre
   [SCIAD063, SAC037]
FX This project was supported by the Rosetrees Trust (M160, M160-F1 and
   M160-F2) and National Eye Research Centre (SCIAD063 and SAC037).
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NR 49
TC 4
Z9 5
U1 2
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD FEB
PY 2020
VL 191
AR 107931
DI 10.1016/j.exer.2020.107931
PG 11
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA KM9UV
UT WOS:000514487100013
PM 31931003
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Wilkerson, JL
   Stiles, MA
   Gurley, JM
   Grambergs, RC
   Gu, XW
   Elliott, MH
   Proia, RL
   Mandal, NA
AF Wilkerson, Joseph L.
   Stiles, Megan A.
   Gurley, Jami M.
   Grambergs, Richard C.
   Gu, Xiaowu
   Elliott, Michael H.
   Proia, Richard L.
   Mandal, Nawajes A.
TI Sphingosine Kinase-1 Is Essential for Maintaining External/Outer
   Limiting Membrane and Associated Adherens Junctions in the Aging Retina
SO MOLECULAR NEUROBIOLOGY
LA English
DT Article
DE Retina; Outer limiting membrane; Sphingosine kinase;
   Sphingosine-1-phosphate; Retinal degeneration; N-cadherin
ID GLASS-ONION LOCUS; PIGMENT EPITHELIUM; KINASE TYPE-2; N-CADHERIN; RAT
   RETINA; SPHINGOSINE-1-PHOSPHATE; INTEGRITY; MORPHOGENESIS; 1-PHOSPHATE;
   ROD
AB Sphingosine-1-phosphate (S1P) produced by sphingosine kinases (SPHK1 and SPHK2) is a signaling molecule involved in cell proliferation and formation of cellular junctions. In this study, we characterized the retinas of Sphk1 knockout (KO) mice by electron microscopy and immunocytochemistry. We also tested cultured Muller glia for their response to S1P. We found that S1P plays an important role in retinal and retinal pigment epithelial (RPE) structural integrity in aging mice. Ultrastructural analysis of Sphk1 KO mouse retinas aged to 15 months or raised with moderate light stress revealed a degenerated outer limiting membrane (OLM). This membrane is formed by adherens junctions between neighboring Muller glia and photoreceptor cells. We also show that Sphk1 KO mice have reduced retinal function in mice raised with moderate light stress. In vitro assays revealed that exogenous S1P modulated cytoskeletal rearrangement and increased N-cadherin production in human Muller glia cells. Aged mice also had morphological degeneration of the RPE, as well as increased lipid storage vacuoles and undigested phagosomes reminiscent of RPE in age-related macular degeneration. These findings show that SPHK1 and S1P play a vital role in the structural maintenance of the mammalian retina and retinal pigmented epithelium by supporting the formation of adherens junctions.
C1 [Wilkerson, Joseph L.; Mandal, Nawajes A.] Univ Oklahoma, Dept Cell Biol, Hlth Sci Ctr, Oklahoma City, OK 73104 USA.
   [Wilkerson, Joseph L.; Stiles, Megan A.; Gurley, Jami M.; Gu, Xiaowu; Elliott, Michael H.; Mandal, Nawajes A.] Dean A McGee Eye Inst, Oklahoma City, OK 73104 USA.
   [Stiles, Megan A.; Gurley, Jami M.; Gu, Xiaowu; Elliott, Michael H.; Mandal, Nawajes A.] Univ Oklahoma, Dept Ophthalmol, Hlth Sci Ctr, Oklahoma City, OK 73104 USA.
   [Grambergs, Richard C.; Mandal, Nawajes A.] Univ Tennessee, Dept Ophthalmol & Anat & Neurobiol, Hlth Sci Ctr, Memphis, TN 38163 USA.
   [Proia, Richard L.] Natl Inst Diabet & Digest & Kidney Dis, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
   [Mandal, Nawajes A.] Univ Tennessee, Hamilton Eye Inst, Dept Ophthalmol, Hlth Sci Ctr, 930 Madison Ave,Suite 718, Memphis, TN 38163 USA.
   [Mandal, Nawajes A.] Univ Tennessee, Hamilton Eye Inst, Dept Anat & Neurobiol, Hlth Sci Ctr, 930 Madison Ave,Suite 718, Memphis, TN 38163 USA.
C3 University of Oklahoma System; University of Oklahoma Health Sciences
   Center; University of Oklahoma System; University of Oklahoma Health
   Sciences Center; University of Tennessee System; University of Tennessee
   Health Science Center; National Institutes of Health (NIH) - USA; NIH
   National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK);
   University of Tennessee System; University of Tennessee Health Science
   Center; University of Tennessee System; University of Tennessee Health
   Science Center
RP Mandal, NA (通讯作者)，Univ Oklahoma, Dept Cell Biol, Hlth Sci Ctr, Oklahoma City, OK 73104 USA.; Mandal, NA (通讯作者)，Dean A McGee Eye Inst, Oklahoma City, OK 73104 USA.; Mandal, NA (通讯作者)，Univ Oklahoma, Dept Ophthalmol, Hlth Sci Ctr, Oklahoma City, OK 73104 USA.; Mandal, NA (通讯作者)，Univ Tennessee, Dept Ophthalmol & Anat & Neurobiol, Hlth Sci Ctr, Memphis, TN 38163 USA.; Mandal, NA (通讯作者)，Univ Tennessee, Hamilton Eye Inst, Dept Ophthalmol, Hlth Sci Ctr, 930 Madison Ave,Suite 718, Memphis, TN 38163 USA.; Mandal, NA (通讯作者)，Univ Tennessee, Hamilton Eye Inst, Dept Anat & Neurobiol, Hlth Sci Ctr, 930 Madison Ave,Suite 718, Memphis, TN 38163 USA.
EM nmandal@uthsc.edu
OI Mandal, NAWAJES/0000-0003-4489-7748; Gurley, Jami/0000-0002-7919-9328;
   Proia, Richard/0000-0003-0456-1270; GU, XIAOWU/0000-0003-2266-5516
FU NIH [EY022071, EY025256, EY021725]; VCU Lipidomics/Metabolomics Core:
   NIH [T32EY023202, P30 CA016059, S10 RR031535]; NATIONAL EYE INSTITUTE
   [R21EY025256, R01EY022071] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [ZIADK056016,
   ZIADK056014] Funding Source: NIH RePORTER
FX NAM: NIH grants EY022071, EY025256, and EY021725 (Foundation Fighting
   Blindness and Research to Prevent Blindness, USA). JLW: T32EY023202 (VCU
   Lipidomics/Metabolomics Core: NIH grants P30 CA016059 and S10 RR031535).
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NR 51
TC 9
Z9 10
U1 2
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0893-7648
EI 1559-1182
J9 MOL NEUROBIOL
JI Mol. Neurobiol.
PD OCT
PY 2019
VL 56
IS 10
BP 7188
EP 7207
DI 10.1007/s12035-019-1599-x
PG 20
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA IX9LQ
UT WOS:000486010800038
PM 30997640
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Bittkau, KS
   Dorschmann, P
   Blumel, M
   Tasdemir, D
   Roider, J
   Klettner, A
   Alban, S
AF Bittkau, Kaya Saskia
   Doerschmann, Philipp
   Bluemel, Martina
   Tasdemir, Deniz
   Roider, Johann
   Klettner, Alexa
   Alban, Susanne
TI Comparison of the Effects of Fucoidans on the Cell Viability of Tumor
   and Non-Tumor Cell Lines
SO MARINE DRUGS
LA English
DT Article
DE Fucus vesiculosus; Fucus serratus; Fucus evanescens; Laminaria digitata;
   Saccharina latissima; Dictyosiphon foeniculaceus; heparin; cancer;
   cytotoxic; antiproliferative
ID ENDOTHELIAL GROWTH-FACTOR; IN-VITRO; SULFATED POLYSACCHARIDES;
   FUCUS-VESICULOSUS; ANTITUMOR-ACTIVITY; OXIDATIVE STRESS; CANCER
   SURVIVAL; BROWN SEAWEEDS; MELANOMA-CELLS; APOPTOSIS
AB Fucoidans extracted from brown algae exert manifold biological activities paving the way for the development of numerous applications including treatments outside tumor therapy such as age-related macular degeneration or tissue engineering. In this study, we investigated the antiproliferative effects of fucoidans extracted from six different algae (Fucus vesiculosus, F. serratus, F. distichus subsp. evanescens, Dictyosiphon foeniculaceus, Laminaria digitata, Saccharina latissima) as well as three reference compounds (Sigma fucoidan, heparin, enoxaparin) on tumor (HL-60, Raji, HeLa, OMM-1, A-375, HCT-116, Hep G2) and non-tumor (ARPE-19, HaCaT) cell lines. All fucoidans were extracted according to a standardized procedure and tested in a commercially available MTS assay. Cell viability was measured after 24 h incubation with test compounds (1-100 mu g/mL). Apart from few exceptions, fucoidans and heparins did not impair cell viability. In contrast, fucoidans significantly increased cell viability of suspension cell lines, but not of adherent cells. Fucoidans slightly increased viability of tumor cells and had no impact on the viability of non-tumor cells. The cell viability of HeLa and ARPE-19 cells negatively correlated with protein content and total phenolic content (TPC) of fucoidans, respectively. In summary, none of the tested fucoidans turned out to be anti-proliferative, rendering them interesting for future studies and applications.
C1 [Bittkau, Kaya Saskia; Alban, Susanne] Univ Kiel, Pharmaceut Inst, Gutenbergstr 76, D-24118 Kiel, Germany.
   [Doerschmann, Philipp; Roider, Johann; Klettner, Alexa] Univ Kiel, Univ Med Ctr, Dept Ophthalmol, Arnold Heller Str 3,Haus 25, D-24105 Kiel, Germany.
   [Bluemel, Martina; Tasdemir, Deniz] GEOMAR Helmholtz Ctr Ocean Res Kiel, Res Unit Marine Nat Prod Chem, GEOMAR Ctr Marine Biotechnol GEOMAR Biotech, Kiel Kanal 44, D-24106 Kiel, Germany.
   [Tasdemir, Deniz] Univ Kiel, Fac Math & Nat Sci, Christian Albrechts Pl 4, D-24118 Kiel, Germany.
C3 University of Kiel; University of Kiel; Schleswig Holstein University
   Hospital; Helmholtz Association; GEOMAR Helmholtz Center for Ocean
   Research Kiel; University of Kiel
RP Alban, S (通讯作者)，Univ Kiel, Pharmaceut Inst, Gutenbergstr 76, D-24118 Kiel, Germany.; Klettner, A (通讯作者)，Univ Kiel, Univ Med Ctr, Dept Ophthalmol, Arnold Heller Str 3,Haus 25, D-24105 Kiel, Germany.
EM alexakarina.klettner@uksh.de; salban@pharmazie.uni-kiel.de
OI Alban, Susanne/0000-0003-1993-3751; Klettner, Alexa/0000-0002-2709-1059
FU InterReg-Deutschland-Denmark; Herrmann -Wacker-Foundation
FX This research was funded by InterReg-Deutschland-Denmark. A.K. was
   funded by the Herrmann -Wacker-Foundation.
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NR 71
TC 17
Z9 18
U1 1
U2 6
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1660-3397
J9 MAR DRUGS
JI Mar. Drugs
PD AUG
PY 2019
VL 17
IS 8
AR 441
DI 10.3390/md17080441
PG 19
WC Chemistry, Medicinal; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA IV6UL
UT WOS:000484403200045
PM 31357497
OA Green Submitted, Green Published, gold, Green Accepted
DA 2022-11-30
ER

PT J
AU Liang, XD
   Wang, ZY
   Gao, M
   Wu, S
   Zhang, JX
   Liu, Q
   Yu, YP
   Wang, J
   Liu, W
AF Liang, Xida
   Wang, Zengyi
   Gao, Meng
   Wu, Shen
   Zhang, Jingxue
   Liu, Qian
   Yu, Yanping
   Wang, Jing
   Liu, Wu
TI Cyclic stretch induced oxidative stress by mitochondrial and NADPH
   oxidase in retinal pigment epithelial cells
SO BMC OPHTHALMOLOGY
LA English
DT Article
DE Cyclic stretch; RPE; Oxidative stress; Age-related macular degeneration
ID ENDOTHELIAL GROWTH-FACTOR; VITREOMACULAR ADHESION; MACULAR DEGENERATION;
   ANGIOTENSIN-II; DNA DAMAGE; SUPEROXIDE; INDUCTION; TRACTION
AB Background: Vitreomacular adhesion (VMA) has been reported to associated with age-related macular degeneration (AMD). Understanding the mechanisms underlying cyclic stretch induced in retinal pigment epithelial cells (RPE) may be important for the treatment of VMA-related AMD.
   Method: Cyclic stretch (1HZ, 20% elongation) was applied to cultured ARPE-19 cells for 15min, 2h, 6h, 12h, 24h by flexcell FX-5000 Tension system. Total reactive oxygen species (ROS) were detected using DCFH-DA. Mitochondrial superoxide were detected using MitoSOX Red mitochondrial superoxide indicator. NADPH oxidases (NOX) and signaling pathways, such as p38 and PKC, were detected using western blot. Apocycin (Apo) were used as NOX inhibitors.
   Result: High levels of total ROS were detected from 15min to 24h, whereas mitochondrial superoxide were higher only in early time. NOX2 were significantly increased at 24h. NOX4 were significantly increased at 2h and reach its peak at 24h. P-p38 was significantly increased at 12h and 24h. P-PKC was significantly increased at 15min and kept a persistent high level. The upregulated expression of NOX4 by cyclic stretch can be significantly decreased under p-PKC inhibitor other than p-p38 inhibitor.
   Conclusion: Cyclic stretch induce oxidative stress from both mitochodrial and NADPH oxidase in RPE cells, which may prompt oxidative damage in VMA-related AMD.
C1 [Liang, Xida; Wang, Zengyi; Gao, Meng; Yu, Yanping; Wang, Jing; Liu, Wu] Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing 100730, Peoples R China.
   [Liang, Xida; Wang, Zengyi; Gao, Meng; Wu, Shen; Zhang, Jingxue; Liu, Qian; Yu, Yanping; Wang, Jing; Liu, Wu] Beijing Ophthalmol & Visual Sci Key Lab, Beijing 100730, Peoples R China.
   [Wu, Shen; Zhang, Jingxue; Liu, Qian] Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing Inst Ophthalmol, Beijing 100730, Peoples R China.
C3 Capital Medical University; Capital Medical University
RP Liu, W (通讯作者)，Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing 100730, Peoples R China.; Liu, W (通讯作者)，Beijing Ophthalmol & Visual Sci Key Lab, Beijing 100730, Peoples R China.
EM wuliubj@sina.com
RI Yu, Yan/GYV-4514-2022; liu, qian/HDM-2936-2022
FU National Nature Science Foundation of China [81541106]
FX This research is financed by the National Nature Science Foundation of
   China (No.81541106), which guide the design of the study and provide the
   necessary reagents used in this study.
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NR 31
TC 13
Z9 14
U1 0
U2 12
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-2415
J9 BMC OPHTHALMOL
JI BMC Ophthalmol.
PD MAR 18
PY 2019
VL 19
AR 79
DI 10.1186/s12886-019-1087-0
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HP7XY
UT WOS:000461905100001
PM 30885167
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Li, YJ
   Zhou, YD
AF Li, Yuanjun
   Zhou, Yedi
TI Interleukin-17: The Role for Pathological Angiogenesis in Ocular
   Neovascular Diseases
SO TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Review
DE cytokine; interleukin-17; ocular neovascular disease; T helper 17 cell;
   vascular endothelial growth factor
ID DELTA-T-CELLS; RECEPTOR ROR-GAMMA; DIABETIC-RETINOPATHY; MACROPHAGE
   ACTIVATION; PROMOTES ANGIOGENESIS; NONCODING RNAS; DOUBLE-BLIND; TH17
   CELLS; CYTOKINES; IL-17
AB Ocular neovascular diseases are featured by abnormal angiogenesis in the eye, and they seriously threaten the human visual health. These diseases include proliferative diabetic retinopathy (PDR), age-related macular degeneration (AMD), retinopathy of prematurity (ROP), and retinal vein occlusion (RVO). In fact, ocular neovascular diseases represent the leading causes of vision impairment and blindness worldwide. Ocular neovascularization, the process of pathological vessel formation in eye, underlies ocular neovascular diseases. Cytokines have important regulatory roles in neovascularization through immunological networks. Interleukin (IL)-17, the signature cytokine produced by T helper 17 (Th17) cells, has proven to be involved in ocular neovascularization. However, roles of IL-17 in ocular neovascular diseases still remain controversial. This review provides an overview of the functional roles of IL-17 in ocular neovascular diseases from basic research to clinical evidence by focusing on PDR, AMD, ROP, and RVO. The possible roles of IL-17 in neovascularization are achieved through a regulatory network of cytoskeleton remodeling, vascular endothelial growth factor (VEGF), VEGF-related cytokines, and complement components. Current applications as well as potential therapies targeting IL-17 with genome editing systems are also outlined and discussed. Targeting IL-17 might be a promising therapeutic strategy against ocular neovascular diseases.
C1 [Li, Yuanjun; Zhou, Yedi] Cent S Univ, Xiangya Hosp 2, Dept Ophthalmol, 139 Middle Renmin Rd, Changsha 410011, Hunan, Peoples R China.
   [Li, Yuanjun] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Dept Ophthalmol, Guangzhou, Guangdong, Peoples R China.
   [Zhou, Yedi] Hunan Clin Res Ctr Ophthalm Dis, Changsha, Hunan, Peoples R China.
C3 Central South University; Sun Yat Sen University
RP Zhou, YD (通讯作者)，Cent S Univ, Xiangya Hosp 2, Dept Ophthalmol, 139 Middle Renmin Rd, Changsha 410011, Hunan, Peoples R China.
EM zhouyedi@csu.edu.cn
OI LI, Yuanjun/0000-0003-4433-6297; Zhou, Yedi/0000-0002-8948-1108
FU National Natural Science Foundation of China [81800855]; Natural Science
   Foundation of Hunan Province [2018JJ3765]; Department of Science and
   Technology, Hunan [2015TP2007]
FX This work was supported by National Natural Science Foundation of China
   (No. 81800855), Natural Science Foundation of Hunan Province (No.
   2018JJ3765), and Department of Science and Technology, Hunan (No.
   2015TP2007).
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NR 119
TC 12
Z9 16
U1 2
U2 4
PU TOHOKU UNIV MEDICAL PRESS
PI SENDAI
PA 2-1, SEIRYO-MACHI, AOBA-KU, SENDAI, MIYAGI 980-8575, JAPAN
SN 0040-8727
EI 1349-3329
J9 TOHOKU J EXP MED
JI Tohoku J. Exp. Med.
PD FEB
PY 2019
VL 247
IS 2
BP 87
EP 98
DI 10.1620/tjem.247.87
PG 12
WC Medicine, General & Internal; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine; Research & Experimental Medicine
GA HP2UM
UT WOS:000461530900003
PM 30773517
OA gold
DA 2022-11-30
ER

PT J
AU Arroba, AI
   Campos-Caro, A
   Aguilar-Diosdado, M
   Valverde, AM
AF Arroba, Ana I.
   Campos-Caro, Antonio
   Aguilar-Diosdado, Manuel
   Valverde, Angela M.
TI IGF-1, Inflammation and Retinal Degeneration: A Close Network
SO FRONTIERS IN AGING NEUROSCIENCE
LA English
DT Review
DE retina; inflammation; neurodegeneration; IGF-1; microglia and exosomes
ID GROWTH-FACTOR-I; RD10 MOUSE MODEL; MACULAR DEGENERATION; MICROGLIAL
   ACTIVATION; DIABETIC-RETINOPATHY; PIGMENT EPITHELIUM; GANGLION-CELLS;
   AQUEOUS-HUMOR; EXPRESSION; EXOSOMES
AB Retinal degenerative diseases are a group of heterogeneous diseases that include age-related macular degeneration (AMD), retinitis pigmentosa (RP), and diabetic retinopathy (DR). The progressive degeneration of the retinal neurons results in a severe deterioration of the visual function. Neuroinflammation is an early hallmark of many neurodegenerative disorders of the retina including AMD, RP and DR.Microglial cells, key components of the retinal immune defense system, are activated in retinal degenerative diseases. In the microglia the interplay between the proinflammatory/classically activated or antiinflammatory/alternatively activated phenotypes is a complex dynamic process that occurs during the course of disease due to the different environmental signals related to pathophysiological conditions. In this regard, an adequate transition from the proinflammatory to the anti-inflammatory response is necessary to counteract retinal neurodegeneration and its subsequent damage that leads to the loss of visual function. Insulin like-growth factor-1 (IGF-1) has been considered as a pleiotropic factor in the retina under health or disease conditions and several effects of IGF-1 in retinal immune modulation have been described. In this review, we provide recent insights of inflammation as a common feature of retinal diseases (AMD, RP and RD) highlighting the role of microglia, exosomes and IGF-1 in this process.
C1 [Arroba, Ana I.; Valverde, Angela M.] CSIC UAM, Alberto Sols Biomed Res Inst IIBm, Madrid, Spain.
   [Arroba, Ana I.; Valverde, Angela M.] ISCIII, Spanish Biomed Res Ctr Diabet & Associated Metab, Madrid, Spain.
   [Arroba, Ana I.; Campos-Caro, Antonio; Aguilar-Diosdado, Manuel] Univ Hosp Puerta del Mar, Inst Invest & Innovac Ciencias Biomed Prov Cadiz, Res Unit, Cadiz, Spain.
   [Aguilar-Diosdado, Manuel] Univ Hosp Puerta del Mar, Inst Invest & Innovac Ciencias Biomed Prov Cadiz, Dept Endocrinol & Metab, Cadiz, Spain.
   [Arroba, Ana I.] Univ Hosp Puerta del Mar, Inst Invest & Innovac Biomed Cadiz INIBICA, Res Unit, Cadiz, Spain.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto
   de Investigaciones Biomedicas Alberto Sols (IIBM); Instituto de Salud
   Carlos III; Universidad de Cadiz; Hospital Universitario Puerta del Mar;
   Universidad de Cadiz; Hospital Universitario Puerta del Mar; Universidad
   de Cadiz; Hospital Universitario Puerta del Mar
RP Arroba, AI; Valverde, AM (通讯作者)，CSIC UAM, Alberto Sols Biomed Res Inst IIBm, Madrid, Spain.; Arroba, AI; Valverde, AM (通讯作者)，ISCIII, Spanish Biomed Res Ctr Diabet & Associated Metab, Madrid, Spain.; Arroba, AI (通讯作者)，Univ Hosp Puerta del Mar, Inst Invest & Innovac Ciencias Biomed Prov Cadiz, Res Unit, Cadiz, Spain.; Arroba, AI (通讯作者)，Univ Hosp Puerta del Mar, Inst Invest & Innovac Biomed Cadiz INIBICA, Res Unit, Cadiz, Spain.
EM anaarroba@gmail.com; avalverde@iib.uam.es
RI Campos-Caro, Antonio/T-2807-2019; AGUILAR-DIOSDADO, MANUEL/A-2549-2009;
   Isabel, Arroba Ana/AAX-5396-2021
OI Campos-Caro, Antonio/0000-0001-8532-2153; AGUILAR-DIOSDADO,
   MANUEL/0000-0001-9657-5949; Isabel, Arroba Ana/0000-0002-5136-1725;
   Martinez Valverde, Angela/0000-0003-1192-9045
FU European Union [721236, 278040]; Spanish Ministry of Economy and
   Competitiveness [SAF2015-65267-R]; Spanish ISCIII (CIBERdem); INFLAMES
   [ISCIII PIE14/00045]; ERDF
FX We acknowledge I. Varela-Nieto, R. Simo, C. Hernandez, E. Beltramo, A.
   Mazzeo, M. Porta, E. M. Sanchez-Fernandez, C. Ortiz Mellet, J. M. Garcia
   Fernandez and L. Masgrau for their input and scientific collaboration.
   The work of AIA and AMV has been funded by grants from European Union
   (project H2020-MSCA-ITN TREATMENT Grant Agreement number: 721236 and
   project EUROCONDOR FP7 Grant Agreement number 278040), grant from the
   Spanish Ministry of Economy and Competitiveness: SAF2015-65267-R
   (MINECO/FEDER) and grants from the Spanish ISCIII (CIBERdem) and
   INFLAMES (ISCIII PIE14/00045, co-funded by ERDF, Investing in your
   future).
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NR 139
TC 35
Z9 37
U1 1
U2 11
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
SN 1663-4365
J9 FRONT AGING NEUROSCI
JI Front. Aging Neurosci.
PD JUL 5
PY 2018
VL 10
AR 203
DI 10.3389/fnagi.2018.00203
PG 12
WC Geriatrics & Gerontology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA GL8FD
UT WOS:000437449900001
PM 30026694
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Zhang, XY
   Ng, TK
   Brelen, ME
   Chan, KP
   Wu, D
   Yung, JSY
   Cao, D
   Wang, YM
   Zhang, SD
   Chan, SO
   Pang, CP
AF Zhang, Xiao-Yu
   Ng, Tsz Kin
   Brelen, Marten Erik
   Chan, Kwok Ping
   Wu, Di
   Yung, Jasmine Sum Yee
   Cao, Di
   Wang, Yumeng
   Zhang, Shaodan
   Chan, Sun On
   Pang, Chi Pui
TI Disruption of retinal pigment epithelial cell properties under the
   exposure of cotinine
SO SCIENTIFIC REPORTS
LA English
DT Article
ID POLYPOIDAL CHOROIDAL VASCULOPATHY; SMOOTH-MUSCLE-CELLS; MACULAR
   DEGENERATION; VEGF-SECRETION; NICOTINE; SMOKING; AUTOPHAGY; HTRA1;
   PROLIFERATION; CONSTITUENT
AB Cigarette smoking is a major risk factor for age-related macular degeneration (AMD), in which progressive retinal pigment epithelial (RPE) cell degeneration is a major pathological change. Nicotine is a major biologically active component in cigarette smoke. It is continuously catabolized into cotinine, which has longer half-life and higher concentration in tissue cells and fluids. Here we hypothesized that continuous exposure of cotinine has more potent effects on human RPE cell properties than nicotine. Human RPE cell line (ARPE-19) was treated continuously with 1-2 mu M of nicotine and/or cotinine for 7 days. RPE cells treated with 2 mu M cotinine and nicotine-cotinine mixture has lower MTT signals without significant changes in cell apoptosis or integrity. Moreover, RPE cell migration was retarded under cotinine treatments, but not nicotine. Both nicotine and cotinine treatments attenuated the phagocytotic activity of RPE cells. In addition, cotinine and nicotine-cotinine mixture suppressed VEGF and IL-8 expression and upregulated TIMP-2 expression. Expressions of autophagy genes were upregulated by the cotinine treatment, whereas expressions of epithelial-to-mesenchymal transition markers were downregulated. In conclusion, our study, for the first time, demonstrated that cotinine, rather than nicotine, affects the properties of RPE cells in vitro, which could explain the smoking-induced RPE pathology.
C1 [Zhang, Xiao-Yu; Ng, Tsz Kin; Brelen, Marten Erik; Chan, Kwok Ping; Yung, Jasmine Sum Yee; Cao, Di; Wang, Yumeng; Pang, Chi Pui] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong, Hong Kong, Peoples R China.
   [Zhang, Xiao-Yu; Wu, Di; Zhang, Shaodan] Fourth Peoples Hosp Shenyang, Dept Ophthalmol, Shenyang, Peoples R China.
   [Zhang, Xiao-Yu; Wu, Di; Zhang, Shaodan] Shenyang Key Lab Ophthalmol, Shenyang, Peoples R China.
   [Chan, Sun On] Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China.
C3 Chinese University of Hong Kong; Chinese University of Hong Kong
RP Ng, TK (通讯作者)，Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong, Hong Kong, Peoples R China.
EM micntk@hotmail.com
RI Brelen, Marten E./D-1133-2016; Chan, Sun-On/R-6547-2018; Ng, Tsz
   Kin/I-8061-2014; Chan, Kwok Ping/E-6044-2016
OI Chan, Sun-On/0000-0002-3221-3786; Ng, Tsz Kin/0000-0001-7863-7229; Chan,
   Kwok Ping/0000-0003-2416-1995; Wang, Yumeng/0000-0002-2282-0814
FU Direct Grant from the Medical Panel, the Chinese University of Hong Kong
   [2014.1.055]; Health and Medical Research Fund, Hong Kong [12130791]
FX We are grateful to Ms. Yolanda W.Y. Yip and Ms. Pancy O.S. Tam for the
   routine laboratory management and maintenance. This study was supported
   by the Direct Grant from the Medical Panel, the Chinese University of
   Hong Kong (grant number: 2014.1.055 to T.K.N.) and the Health and
   Medical Research Fund (project number: 12130791 to T.K.N.), Hong Kong.
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NR 37
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Z9 11
U1 0
U2 8
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 JUN 9
PY 2017
VL 7
AR 3139
DI 10.1038/s41598-017-03283-x
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA EX1CM
UT WOS:000402957400020
PM 28600524
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Luckoff, A
   Scholz, R
   Sennlaub, F
   Xu, HP
   Langmann, T
AF Lueckoff, Anika
   Scholz, Rebecca
   Sennlaub, Florian
   Xu, Heping
   Langmann, Thomas
TI Comprehensive analysis of mouse retinal mononuclear phagocytes
SO NATURE PROTOCOLS
LA English
DT Article
ID INDUCED CHOROIDAL NEOVASCULARIZATION; ACTIVATED MICROGLIA/MACROPHAGE;
   PHOTORECEPTOR DEGENERATION; MACULAR DEGENERATION; IN-VIVO; MICROGLIAL
   PHAGOCYTOSIS; SUBRETINAL INFLAMMATION; RETINITIS-PIGMENTOSA; AGE; MODEL
AB The innate immune system is activated in a number of degenerative and inflammatory retinal disorders such as age-related macular degeneration (AMD). Retinal microglia, choroidal macrophages, and recruited monocytes, collectively termed 'retinal mononuclear phagocytes', are critical determinants of ocular disease outcome. Many publications have described the presence of these cells in mouse models for retinal disease; however, only limited aspects of their behavior have been uncovered, and these have only been uncovered using a single detection method. The workflow presented here describes a comprehensive analysis strategy that allows characterization of retinal mononuclear phagocytes in vivo and in situ. We present standardized working steps for scanning laser ophthalmoscopy of microglia from MacGreen reporter mice (mice expressing the macrophage colony-stimulating factor receptor GFP transgene throughout the mononuclear phagocyte system), quantitative analysis of Iba1-stained retinal sections and flat mounts, CD11b-based retinal flow cytometry, and qRTRT-PCRPCRPCR analysis of key microglia markers. The protocol can be completed within 3 d, and we present data from retinas treated with laser-induced choroidal neovascularization (CNCNV), bright white-light exposure, and Fam161a-associated inherited retinal degeneration. The assays can be applied to any of the existing mouse models for retinal disorders and may be valuable for documenting immune responses in studies for immunomodulatory therapies.
C1 [Lueckoff, Anika; Scholz, Rebecca; Langmann, Thomas] Univ Cologne, Dept Ophthalmol, Lab Expt Immunol Eye, Cologne, Germany.
   [Sennlaub, Florian] Univ Paris 06, Sorbonne Univ, Inst Vis, CNRS,INSERM, Paris, France.
   [Xu, Heping] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Ctr Expt Med, Belfast, Antrim, North Ireland.
C3 University of Cologne; 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; Queens University Belfast
RP Langmann, T (通讯作者)，Univ Cologne, Dept Ophthalmol, Lab Expt Immunol Eye, Cologne, Germany.
EM thomas.langmann@uk-koeln.de
RI Xu, Heping/A-4430-2008; Sennlaub, Florian/F-2756-2017
OI Xu, Heping/0000-0003-4000-931X; Sennlaub, Florian/0000-0003-4412-1341
FU German Research Foundation (DFG) [LA1203/6-2, LA1203/9-1, LA1203/10-1,
   FOR2240]; ProRetina Foundation; Hans and Marlies Stock Foundation; Velux
   Foundation; Fight for Sight [1425/1426]; Germany's Federal Ministry of
   Education and Research (BMBF) [03VP00272]; Graduate Program in
   Pharmacology and Experimental Therapeutics at the University of Cologne;
   Bayer; INSERM; Agence Nationale de la Recherche (ANR) MACLEAR
   [ANR-15-CE14-0015-01]; Labex LifeSenses [ANR-10-LABX-65]; ANR
   (Investissements d'Avenir programme) [ANR-11-IDEX-0004-02]; Carnot; ERC
   [ERC-2007 St.G. 210345]; Association de Prevoyance Sante de ALLIANZ;
   Fight for Sight [1361/62] Funding Source: researchfish
FX This work was supported by grants from the German Research Foundation
   (DFG; LA1203/6-2, LA1203/9-1, LA1203/10-1, and FOR2240), the ProRetina
   Foundation, the Hans and Marlies Stock Foundation, the Velux Foundation,
   Fight for Sight (1425/1426), Germany's Federal Ministry of Education and
   Research (BMBF; 03VP00272), the Graduate Program in Pharmacology and
   Experimental Therapeutics at the University of Cologne (in collaboration
   with Bayer), INSERM, Agence Nationale de la Recherche (ANR) MACLEAR
   (ANR-15-CE14-0015-01), Labex LifeSenses (ANR-10-LABX-65), the ANR
   (Investissements d'Avenir programme (ANR-11-IDEX-0004-02)), Carnot, the
   ERC (starting grant ERC-2007 St.G. 210345), and the Association de
   Prevoyance Sante de ALLIANZ.
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NR 55
TC 35
Z9 36
U1 1
U2 22
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1754-2189
EI 1750-2799
J9 NAT PROTOC
JI Nat. Protoc.
PD JUN
PY 2017
VL 12
IS 6
BP 1136
EP 1150
DI 10.1038/nprot.2017.032
PG 15
WC Biochemical Research Methods
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA EU5YA
UT WOS:000401109200003
PM 28471458
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Adamson, P
   Wilde, T
   Dobrzynski, E
   Sychterz, C
   Polskyc, R
   Kurali, E
   Haworth, R
   Tang, CM
   Korczynska, J
   Cook, F
   Papanicolaou, I
   Tsikna, L
   Roberts, C
   Hughes-Thomas, Z
   Walford, J
   Gibson, D
   Warrack, J
   Smal, J
   Verrijk, R
   Miller, PE
   Nork, TM
   Prusakiewicz, J
   Streit, T
   Sorden, S
   Struble, C
   Christian, B
   Catchpole, IR
AF Adamson, Peter
   Wilde, Thomas
   Dobrzynski, Eric
   Sychterz, Caroline
   Polskyc, Rodd
   Kurali, Edit
   Haworth, Richard
   Tang, Chi-Man
   Korczynska, Justyna
   Cook, Fiona
   Papanicolaou, Irene
   Tsikna, Lemy
   Roberts, Chris
   Hughes-Thomas, Zoe
   Walford, James
   Gibson, Daniel
   Warrack, John
   Smal, Jos
   Verrijk, Ruud
   Miller, Paul E.
   Nork, T. Michael
   Prusakiewicz, Jeffery
   Streit, Timothy
   Sorden, Steven
   Struble, Craig
   Christian, Brian
   Catchpole, Ian R.
TI Single ocular injection of a sustained-release anti-VEGF delivers 6
   months pharmacokinetics and efficacy in a primate laser CNV model
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article
DE VEGF; Choroidal neovascularisation; Sustained-release delivery;
   Intraocular injection; Microspheres; Non-human primate eyes
ID ENDOTHELIAL GROWTH-FACTOR; EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION;
   IN-VIVO EVALUATION; MACULAR DEGENERATION; MONKEY EYES; BIOCOMPATIBILITY;
   MICROSPHERES; ACCOMMODATION; BEVACIZUMAB; DEGRADATION
AB A potent anti-vascular endothelial growth factor (VEGF) biologic and a compatible delivery system were co-evaluated for protection against wet age-related macular degeneration (AMD) over a 6 month period following a single intravitreal (IVT) injection. The anti-VEGF molecule is dimeric, containing two different anti-VEGF domain antibodies (dAb) attached to a human IgG1 Fc region: a dual dAb. The delivery system is based on microparticles of PolyActive (TM) hydrogel co-polymer. The molecule was evaluated both in vitro for potency against VEGF and in ocular VEGF-driven efficacy models in vivo. The dual dAb is highly potent, showing a lower IC50 than aflibercept in VEGF receptor binding assays (RBAs) and retaining activity upon release from microparticles over 12 months in vitro. Microparticles released functional dual dAb in rabbit and primate eyes over 6 months at sufficient levels to protect Cynomolgus against laser-induced grade IV choroidal neovascularisation (CNV). This demonstrates proof of concept for delivery of an anti-VEGF molecule within a sustained-release system, showing protection in a preclinical primate model of wet AMD over 6 months. Polymer breakdown and movement of microparticles in the eye may limit development of particle-based approaches for sustained release after IVT injection. (C) 2016 The Authors. Published by Elsevier B.V.
C1 [Adamson, Peter; Catchpole, Ian R.] GSK Ophthalmol, Stevenage, Herts, England.
   [Wilde, Thomas; Dobrzynski, Eric; Sychterz, Caroline] Drug Metab & Pharmacokinet, London, England.
   [Polskyc, Rodd; Haworth, Richard] Safety Assessment, King Of Prussia, PA USA.
   [Kurali, Edit] Target Sci Stat, Leiden, Netherlands.
   [Tang, Chi-Man; Papanicolaou, Irene; Catchpole, Ian R.] BioPharm Innovat, Madison, WI USA.
   [Korczynska, Justyna; Cook, Fiona; Tsikna, Lemy; Roberts, Chris; Hughes-Thomas, Zoe] BioPharm Discovery, Madison, WI USA.
   [Walford, James; Gibson, Daniel] BioPharm Proc Res, Zernikedreef 9, NL-2333 CR Leiden, Netherlands.
   [Warrack, John] AnalyticalSciences, Granta Pk, Cambridge, England.
   [Adamson, Peter; Wilde, Thomas; Dobrzynski, Eric; Sychterz, Caroline; Polskyc, Rodd; Kurali, Edit] GSK, King Of Prussia, PA USA.
   [Haworth, Richard] GSK Ware, Ware, Herts, England.
   [Tang, Chi-Man; Korczynska, Justyna; Cook, Fiona; Papanicolaou, Irene; Tsikna, Lemy; Roberts, Chris; Hughes-Thomas, Zoe; Walford, James; Gibson, Daniel; Warrack, John; Catchpole, Ian R.] GSK Med Res Ctr, Gunnels Wood Rd, Stevenage SG1 2NY, Herts, England.
   [Smal, Jos; Verrijk, Ruud] OctoPlus NV, Leiden, Netherlands.
   [Miller, Paul E.; Nork, T. Michael] OSOD, Madison, WI USA.
   [Nork, T. Michael] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
   [Prusakiewicz, Jeffery; Streit, Timothy; Sorden, Steven; Struble, Craig; Christian, Brian] Covance, Madison, WI USA.
   [Adamson, Peter] ProQR Therapeut NV, Zernikedreef 9, NL-2333 CR Leiden, Netherlands.
   [Tang, Chi-Man] MedImmune, Granta Pk, Cambridge, England.
   [Tsikna, Lemy] Avacta Life Sci, Cambridge, England.
   [Wilde, Thomas] Janssen Res & Dev, Spring House, PA 19002 USA.
C3 GlaxoSmithKline; GlaxoSmithKline; GlaxoSmithKline; GlaxoSmithKline;
   GlaxoSmithKline; University of Wisconsin System; University of Wisconsin
   Madison; Covance; AstraZeneca; Medimmune; Johnson & Johnson; Janssen
   Pharmaceuticals
RP Catchpole, IR (通讯作者)，GSK Med Res Ctr, Gunnels Wood Rd, Stevenage SG1 2NY, Herts, England.
EM ian.r.catchpole@gsk.com
OI Adamson, Peter/0000-0001-8234-1818
FU GSK; NATIONAL EYE INSTITUTE [P30EY016665] Funding Source: NIH RePORTER
FX GSK funded the work.
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NR 37
TC 36
Z9 36
U1 1
U2 33
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-3659
EI 1873-4995
J9 J CONTROL RELEASE
JI J. Control. Release
PD DEC 28
PY 2016
VL 244
BP 1
EP 13
DI 10.1016/j.jconrel.2016.10.026
PN A
PG 13
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry; Pharmacology & Pharmacy
GA EE4QO
UT WOS:000389590000001
PM 27810558
OA Green Accepted, hybrid
DA 2022-11-30
ER

PT J
AU Geneva, II
AF Geneva, Ivayla I.
TI Photobiomodulation for the treatment of retinal diseases: a review
SO INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
LA English
DT Review
DE photobiomodulation; low level laser therapy; age-related macular
   degeneration; retinopathy of prematurity; far-red to near-infrared;
   retinal degeneration; amblyopia; retinitis pigmentosa; methanol toxicity
ID LEVEL LASER THERAPY; CENTRAL-NERVOUS-SYSTEM; CYTOCHROME-C-OXIDASE;
   LIGHT-INDUCED DAMAGE; 670 NM LIGHT; RETINITIS-PIGMENTOSA; RED-LIGHT;
   GLUTAMINE-SYNTHETASE; INFRARED RADIATION; PERIPHERAL-NERVE
AB Photobiomodulation (PBM), also known as low level laser therapy, has recently risen to the attention of the ophthalmology community as a promising new approach to treat a variety of retinal conditions including age related macular degeneration, retinopathy of prematurity, diabetic retinopathy, Leber's hereditary optic neuropathy, amblyopia, methanol -induced retinal damage, and possibly others. This review evaluates the existing research pertaining to PBM applications in the retina, with a focus on the mechanisms of action and clinical outcomes. All available literature until April 2015 was reviewed using PubMed and the following keywords: "photobiomodulation AND retina", "low level light therapy AND retina", "low level laser therapy AND retina", and "FR/NIR therapy AND retina". In addition, the relevant references listed within the papers identified through PubMed were incorporated. The literature supports the conclusion that the low -cost and non invasive nature of PBM, coupled with the first promising clinical reports and the numerous preclinical -studies in animal models, make PBM well -poised to become an important player in the treatment of a wide range of retinal disorders. Nevertheless, large-scale clinical trials will be necessary to establish the PBM therapeutic ranges for the various retinal diseases, as well as to gain a deeper understanding of its mechanisms of action.
C1 [Geneva, Ivayla I.] SUNY Upstate Med Univ, Dept Ophthalmol, Ctr Vis Res, Syracuse, NY 13202 USA.
C3 State University of New York (SUNY) System; State University of New York
   (SUNY) Upstate Medical Center
RP Geneva, II (通讯作者)，SUNY Upstate Med Univ, Dept Ophthalmol, Ctr Vis Res, 505 Irving Ave, Syracuse, NY 13202 USA.
EM geneva.ivayla@gmail.com
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NR 56
TC 40
Z9 46
U1 0
U2 33
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 2016
VL 9
IS 1
BP 145
EP 152
DI 10.18240/ijo.2016.01.24
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DA4HB
UT WOS:000367759700024
PM 26949625
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Khazaei, M
   Siddiqui, AM
   Fehlings, MG
AF Khazaei, Mohamad
   Siddiqui, Ahad M.
   Fehlings, Michael G.
TI The Potential for iPS-Derived Stem Cells as a Therapeutic Strategy for
   Spinal Cord Injury: Opportunities and Challenges
SO JOURNAL OF CLINICAL MEDICINE
LA English
DT Review
DE spinal cord injury; clinical translation; neuroprotection; cell therapy;
   neuroregeneration
ID ADULT HUMAN FIBROBLASTS; NEURAL STEM/PROGENITOR CELLS; PROMOTE LOCOMOTOR
   RECOVERY; FUNCTIONAL RECOVERY; DIRECT CONVERSION; PROGENITOR CELLS;
   BONE-MARROW; DIRECTED DIFFERENTIATION; EFFICIENT GENERATION; MOUSE
   FIBROBLASTS
AB Spinal cord injury (SCI) is a devastating trauma causing long-lasting disability. Although advances have occurred in the last decade in the medical, surgical and rehabilitative treatments of SCI, the therapeutic approaches are still not ideal. The use of cell transplantation as a therapeutic strategy for the treatment of SCI is promising, particularly since it can target cell replacement, neuroprotection and regeneration. Cell therapies for treating SCI are limited due to several translational roadblocks, including ethical and practical concerns regarding cell sources. The use of iPSCs has been particularly attractive, since they avoid the ethical and moral concerns that surround other stem cells. Furthermore, various cell types with potential for application in the treatment of SCI can be created from autologous sources using iPSCs. For applications in SCI, the iPSCs can be differentiated into neural precursor cells, neurons, oligodendrocytes, astrocytes, neural crest cells and mesenchymal stromal cells that can act by replacing lost cells or providing environmental support. Some methods, such as direct reprogramming, are being investigated to reduce tumorigenicity and improve reprogramming efficiencies, which have been some of the issues surrounding the use of iPSCs clinically to date. Recently, iPSCs have entered clinical trials for use in age-related macular degeneration, further supporting their promise for translation in other conditions, including SCI.
C1 [Khazaei, Mohamad; Siddiqui, Ahad M.; Fehlings, Michael G.] Univ Hlth Network, Toronto Western Res Inst, Dept Genet & Dev, Toronto, ON M5T 2S8, Canada.
   [Fehlings, Michael G.] Univ Toronto, Dept Surg, Toronto, ON M5T 1P5, Canada.
   [Fehlings, Michael G.] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada.
C3 University of Toronto; University Toronto Affiliates; University Health
   Network Toronto; University of Toronto; University of Toronto
RP Fehlings, MG (通讯作者)，Univ Hlth Network, Toronto Western Res Inst, Dept Genet & Dev, Toronto, ON M5T 2S8, Canada.
EM mohamad.r.khazaei@gmail.com; ahadmsiddiqui@gmail.com;
   Michael.Fehlings@uhn.on.ca
RI Siddiqui, Ahad M./AET-0979-2022
OI Siddiqui, Ahad M./0000-0003-3334-1728; Fehlings,
   Michael/0000-0002-5722-6364
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NR 149
TC 14
Z9 14
U1 0
U2 14
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 JAN
PY 2015
VL 4
IS 1
BP 37
EP 65
DI 10.3390/jcm4010037
PG 29
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA CT9II
UT WOS:000363130100004
PM 26237017
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Yagasaki, R
   Nakahara, T
   Ushikubo, H
   Mori, A
   Sakamoto, K
   Ishii, K
AF Yagasaki, Rina
   Nakahara, Tsutomu
   Ushikubo, Hiroko
   Mori, Asami
   Sakamoto, Kenji
   Ishii, Kunio
TI Anti-angiogenic Effects of Mammalian Target of Rapamycin Inhibitors in a
   Mouse Model of Oxygen-Induced Retinopathy
SO BIOLOGICAL & PHARMACEUTICAL BULLETIN
LA English
DT Article
DE mammalian target of rapamycin; pathologic angiogenesis; retina; vascular
   endothelial growth factor
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL VASCULAR DEVELOPMENT; INTRAVITREAL
   BEVACIZUMAB; MACULAR DEGENERATION; SURVIVAL FACTOR; EXPRESSION;
   NEOVASCULARIZATION; MICE; PREMATURITY; APELIN
AB Ocular pathologic angiogenesis is a causative factor for retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. In the present study, we examined the effects of rapamycin and everolimus, inhibitors of mammalian target of rapamycin (mTOR), on retinal pathologic angiogenesis in mice with oxygen-induced retinopathy (OIR), an animal model of proliferative ischemic retinopathy. Mice were exposed to 80% oxygen from postnatal day (P) 7 to P10, and were then brought into room air and subcutaneously injected with rapamycin and everolimus. The neovascular tufts, the size of the central avascular zone, and the immunoreactivity for phosphorylated ribosomal protein S6 (pS6), a downstream indicator of mTOR activity, were evaluated in fiat-mounted retinas. Retinal neovascular tufts and vascular growth in the avascular zone were observed in P15 mice with OIR. In addition, intense immunoreactivity for pS6 was detected in the neovascular tufts and in endothelial cells located at the vascular-avascular border. Both rapamycin and everolimus reduced the extent of retinal neovascular tufts and pS6 immunoreactivity, but they also increased the size of the avascular zone. Thus, activation of the mTOR pathway in endothelial cells contributes to retinal pathologic angiogenesis, and mTOR inhibitors that target proliferating endothelial cells are promising candidates as anti-angiogenic agents for the treatment of vasoproliferative retinal diseases.
C1 [Yagasaki, Rina; Nakahara, Tsutomu; Ushikubo, Hiroko; Mori, Asami; Sakamoto, Kenji; Ishii, Kunio] Kitasato Univ, Sch Pharmaceut Sci, Dept Mol Pharmacol, Minato Ku, Tokyo 1088641, Japan.
C3 Kitasato University
RP Nakahara, T (通讯作者)，Kitasato Univ, Sch Pharmaceut Sci, Dept Mol Pharmacol, Minato Ku, 5-9-1 Shirokane, Tokyo 1088641, Japan.
EM nakaharat@pharm.kitasato-u.ac.jp
OI Sakamoto, Kenji/0000-0003-1326-6580
FU Ministry of Education, Culture, Sports, Science and Technology of Japan
   [23122517, 25122712, 23590112]
FX This study was supported by Grants-in-Aid for Scientific Research on
   Innovative Areas (Nos. 23122517, 25122712, T.N.) and a Grant-in-Aid for
   Scientific Research (C) (No. 23590112, T.N.) from the Ministry of
   Education, Culture, Sports, Science and Technology of Japan.
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NR 22
TC 35
Z9 36
U1 0
U2 1
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 NOV
PY 2014
VL 37
IS 11
BP 1838
EP 1842
DI 10.1248/bpb.b14-00487
PG 5
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA AS0JW
UT WOS:000343964500020
PM 25366488
OA gold
DA 2022-11-30
ER

PT J
AU Geck, U
   Pustolla, N
   Baraki, H
   Atili, A
   Feltgen, N
   Hoerauf, H
AF Geck, Ulrich
   Pustolla, Nicole
   Baraki, Husnia
   Atili, Abed
   Feltgen, Nicolas
   Hoerauf, Hans
TI Posterior vitreous detachment following intravitreal drug injection
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Vitreous; Intravitreal; Injection; Retina
ID DIABETIC MACULAR EDEMA; OPTICAL COHERENCE TOMOGRAPHY; VITREOMACULAR
   TRACTION; DEGENERATION; VITRECTOMY; ADHESION; EYES
AB To evaluate the incidence of posterior vitreous detachment (PVD) induced by intravitreal injection of different intravitreal drugs.
   This prospective observational study included 61 patients (61 eyes) with different underlying retinal diseases: exudative age-related macular degeneration (n = 47), cystoid macular edema (CME) after retinal vein occlusion (n = 8), and CME of other origin (n = 6). Bevazicumab (1.25 mg) was injected into 25 eyes, ranibizumab (0.5 mg) into 27 eyes, triamcinolone (4 mg) into six eyes, and a combination of bevacizumab and triamcinolone into three eyes. Patients with initial PVD were excluded. Patients were followed for at least 4-6 weeks after their last injection by Fourier-domain OCT, fundus biomicroscopy and ultrasound B-examination.
   Overall, 15 of 61 eyes developed a PVD after intravitreal injection (n = 6 after ranibizumab, n = 7 after bevacizumab and n = 2 after triamcinolon) within a mean follow-up period of 11.1 weeks. PVD occurred in three eyes after the first injection, in three eyes after the second, and in seven eyes after the third injection. Incidence of PVD correlated with increasing age.
   Intravitreal injection of commonly-used drugs seems to induce posterior vitreous detachment, which may thus influence the outcome of the underlying disease.
C1 [Geck, Ulrich; Pustolla, Nicole; Baraki, Husnia; Atili, Abed; Feltgen, Nicolas; Hoerauf, Hans] Univ Med Gottingen, Augenklin, D-37075 Gottingen, Germany.
C3 University of Gottingen; University of Hamburg; University Medical
   Center Hamburg-Eppendorf
RP Geck, U (通讯作者)，Univ Med Gottingen, Augenklin, Robert Koch Str 40, D-37075 Gottingen, Germany.
EM ugeck@web.de
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   Stalmans P, 2010, RETINA-J RET VIT DIS, V30, P1122, DOI 10.1097/IAE.0b013e3181e0970a
   Weber-Krause Brigitte, 1996, Ophthalmologe, V93, P660, DOI 10.1007/s003470050054
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NR 18
TC 49
Z9 49
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD JUL
PY 2013
VL 251
IS 7
BP 1691
EP 1695
DI 10.1007/s00417-013-2266-y
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 164CP
UT WOS:000320386700006
PM 23381655
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Duncan, KG
   Hosseini, K
   Bailey, KR
   Yang, H
   Lowe, RJ
   Matthes, MT
   Kane, JP
   LaVail, MM
   Schwartz, DM
   Duncan, JL
AF Duncan, K. G.
   Hosseini, K.
   Bailey, K. R.
   Yang, H.
   Lowe, R. J.
   Matthes, M. T.
   Kane, J. P.
   LaVail, M. M.
   Schwartz, D. M.
   Duncan, J. L.
TI Expression of reverse cholesterol transport proteins ATP-binding
   cassette A1 (ABCA1) and scavenger receptor BI (SR-BI) in the retina and
   retinal pigment epithelium
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID APOLIPOPROTEIN-E; LIPID TRANSPORT; CELLS; DEPOSITS; DISEASE
AB Aims: Excessive lipid accumulation in Bruch's membrane (BrM) is a hallmark of ageing, the major risk factor for age-related macular degeneration (AMD). Retinal pigment epithelial (RPE) cells may utilise reverse cholesterol transport (RCT) activity to move lipid into BrM, mediated through ATP-binding cassette A1 (ABCA1) and scavenger receptor BI (SR-BI).
   Methods: ABCA1 expression was assessed by reverse transcription polymerase chain reaction (RT-PCR) and western blotting of human RPE cell extracts. Lipid transport assays were performed using radiolabelled photoreceptor outer segments (POS). ABCA1 and SR-BI expression was examined in normal mouse eyes by immunofluorescence staining. BrMs of ABCA1 and SR-BI heterozygous mice were examined microscopically.
   Results: Human RPE cells expressed ABCA1 mRNA and protein. The ABCA1 and SR-BI inhibitor glyburide (also known as glibenclamide) abolished basal transport of POS-derived lipids in RPE cells in the presence of highdensity lipoprotein. Mouse retina and RPE expressed ABCA1 and SR-BI. SR-BI was highly expressed in RPE. BrMs were significantly thickened in SR-BI heterozygous mice, but not in ABCA1 heterozygous mice.
   Conclusion: RPE cells express ABCA1 and SR-BI. This implies a significant role for SR-BI and ABCA1 in lipid transport and RCT in the retina and RPE.
C1 [Duncan, K. G.; Hosseini, K.; Bailey, K. R.; Yang, H.; Lowe, R. J.; Matthes, M. T.; LaVail, M. M.; Schwartz, D. M.; Duncan, J. L.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA.
   [Bailey, K. R.; Schwartz, D. M.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA.
   [Kane, J. P.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA.
C3 University of California System; University of California San Francisco;
   US Department of Veterans Affairs; Veterans Health Administration (VHA);
   University of California System; University of California San Francisco
RP Schwartz, DM (通讯作者)，Univ Calif San Francisco, Dept Ophthalmol, Box 0730, San Francisco, CA 94143 USA.
EM schwartz7@mindspring.com
FU Career Development Award; Center Grant from the Foundation Fighting
   Blindness; Dennis Jahnigen Career Development Scholars Award; NIH-NEI
   [EY00415, EY01919, EY002162]; NATIONAL EYE INSTITUTE [Z01EY000415,
   K08EY000415, R37EY001919, P30EY002162, R01EY001919] Funding Source: NIH
   RePORTER
FX Supported by a Physician Scientist Award (JLD); Unrestricted Grant from
   Research to Prevent Blindness - a Career Development Award (JLD); Center
   Grant from the Foundation Fighting Blindness (MML, JLD); the Dennis
   Jahnigen Career Development Scholars Award (JLD); NIH-NEI grants EY00415
   (JLD), EY01919 and EY002162 (MML); That Man May See, Inc. (MML, JLD);
   The Bernard A. Newcomb Macular Degeneration Fund (JLD); Hope for Vision
   (JLD); and the Karl Kirchgessner Foundation (JLD).
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NR 24
TC 71
Z9 70
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 AUG
PY 2009
VL 93
IS 8
BP 1116
EP 1120
DI 10.1136/bjo.2008.144006
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 474RP
UT WOS:000268302000027
PM 19304587
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Berendschot, TTJM
   Plat, J
   de Jong, A
   Mensink, RP
AF Berendschot, Tos T. J. M.
   Plat, Jogchum
   de Jong, Arienne
   Mensink, Ronald P.
TI Long-term plant stanol and sterol ester-enriched functional food
   consumption, serum lutein/zeaxanthin concentration and macular pigment
   optical density
SO BRITISH JOURNAL OF NUTRITION
LA English
DT Article
DE Macular pigment optical density; Plant stanols; Plant sterols;
   Carotenoids
ID AGE-RELATED MACULOPATHY; CAROTENOID CONCENTRATIONS; TISSUE
   CONCENTRATIONS; LUTEIN; ZEAXANTHIN; DEGENERATION; PLASMA; RISK;
   POPULATION; SAMPLE
AB Observational epidemiological studies have shown that low carotenoid intake and/or low carotenoid blood levels increase the risk of degenerative diseases like age-related macular degeneration. Functional foods enriched with plant sterol or stanol esters may lower serum concentrations of fat-soluble carotenoids. Theoretically, as a result the macular pigment optical density (MPOD), a marker for eye health, may change. We carried out a double-blind placebo-controlled human intervention trial with a duration of 18 months to evaluate the possible effects of plant stanol and sterol esters on serum lutein/zeaxanthine concentration in relation to the MPOD. Forty-seven subjects were randomly assigned to one of the three treatment groups: margarine without added plant sterols or stanols, plant sterol-enriched margarine, or plant stanol-enriched margarine. Serum cholesterol and lutein/zeaxanthine concentrations and the MPOD were evaluated at baseline and at study end. Changes in lipid-adjusted serum lutein/zeaxanthine concentrations between baseline and study end differed significantly between the three groups (P=0.001). We found no differences in the MPOD between the three treatment groups, despite the differences in both absolute and cholesterol-standardized serum lutein/zeaxanthine concentrations. This shows that the observed reduction in serum carotenoid concentrations during 18 months consumption of these functional foods does not affect MPOD.
C1 [Berendschot, Tos T. J. M.] Univ Eve Clin maastricht, NL-6202 AZ Maastricht, Netherlands.
   [Plat, Jogchum; de Jong, Arienne; Mensink, Ronald P.] Univ Maastricht, Dept Human Biol, NL-6200 MD Maastricht, Netherlands.
C3 Maastricht University; Maastricht University Medical Centre (MUMC);
   Maastricht University
RP Berendschot, TTJM (通讯作者)，Univ Eve Clin maastricht, POB 5800, NL-6202 AZ Maastricht, Netherlands.
EM t.berendschot@ohk.unimaas.nl
RI Berendschot, Tos TJM/M-8509-2016
OI Berendschot, Tos TJM/0000-0002-8101-939X
CR Beatty S, 2001, INVEST OPHTH VIS SCI, V42, P439
   Berendschot TTJM, 2000, INVEST OPHTH VIS SCI, V41, P3322
   Berendschot TTJM, 2004, ARCH BIOCHEM BIOPHYS, V430, P149, DOI 10.1016/j.abb.2004.04.029
   Berendschot TTJM, 2002, INVEST OPHTH VIS SCI, V43, P1928
   Bone RA, 2003, J NUTR, V133, P992, DOI 10.1093/jn/133.4.992
   Bone RA, 2001, INVEST OPHTH VIS SCI, V42, P235
   Broekmans WMR, 2003, J NUTR, V133, P720, DOI 10.1093/jn/133.3.720
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   Johnson EJ, 2000, AM J CLIN NUTR, V71, P1555
   Kanis MJ, 2007, GRAEF ARCH CLIN EXP, V245, P767, DOI 10.1007/s00417-006-0478-0
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   Trumbo PR, 2006, AM J CLIN NUTR, V84, P971, DOI 10.1093/ajcn/84.5.971
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   Zagers NPA, 2002, APPL OPTICS, V41, P4686, DOI 10.1364/AO.41.004686
NR 29
TC 10
Z9 12
U1 0
U2 2
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 0007-1145
J9 BRIT J NUTR
JI Br. J. Nutr.
PD JUN 14
PY 2009
VL 101
IS 11
BP 1607
EP 1610
DI 10.1017/S0007114508111448
PG 4
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA 463XW
UT WOS:000267468400004
PM 18986598
OA Bronze
DA 2022-11-30
ER

PT J
AU D'souza, YB
   Jones, CJP
   Short, CD
   Roberts, ISD
   Bonshek, RE
AF D'souza, Yvonne B.
   Jones, Carolyn J. P.
   Short, Colin D.
   Roberts, Ian S. D.
   Bonshek, Richard E.
TI Oligosaccharide composition is similar in drusen and dense deposits in
   membranoproliferative glomerulonephritis type II
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE dense deposit disease; drusen; membranoproliferative glomerulonephritis;
   oligosaccharides
ID MACULAR DEGENERATION; FUNDUS CHANGES; COMPLEMENT; DISEASE;
   GLYCOPROTEINS; BINDING
AB Drusen are a feature of age-related macular degeneration (AMD). Lesions similar in appearance to drusen are also found in the fundi of patients with membranoproliferative glomerulonephritis type II (dense deposit disease, DDD). The lamina densa of the glomerular basement membrane, in DDD, is transformed into an electron-dense structure by deposition of microscopically homogeneous material. Our study sought to compare the saccharide composition of drusen and dense deposits in the formalin-fixed, paraffin-embedded tissue from the eye and kidney. Six eye specimens were obtained from patients diagnosed with AMD but another eye was obtained from a patient with partial lipodystrophy, who died after renal failure presumably because of DDD. The kidney specimens were from three biopsy-proven cases of DDD. Glycosylation patterns were measured by the binding of 19 biotinylated lectins before and after neuraminidase pre-treatment. High mannose, bi/tri-antennary non-bisected and bisected complex N-glycan, N-acetyl glucosamine, galactose, and sialic acid residues were found in both drusen and dense deposits. Treatment with neuraminidase exposed subterminal galactose in both sites and sparse N-acetyl galactosamine residues in drusen alone. Our study found similar pathologic oligosaccharide structures in the eye and kidney, suggesting that drusen may be a common end result of retinal and glomerular disease.
C1 [D'souza, Yvonne B.; Bonshek, Richard E.] Manchester Royal Eye Hosp, Acad Unit, Manchester M13 9WH, Lancs, England.
   [Jones, Carolyn J. P.] Univ Manchester, Maternal & Fetal Hlth Res Ctr, Manchester, Lancs, England.
   [Short, Colin D.] Manchester Royal Infirm, Dept Nephrol, Manchester M13 9WL, Lancs, England.
   [Roberts, Ian S. D.] John Radcliffe Hosp, Dept Cellular Pathol, Oxford OX3 9DU, England.
   [Bonshek, Richard E.] Manchester Royal Infirm, NSOPS, Manchester, Lancs, England.
C3 Manchester Royal Eye Hospital; University of Manchester; University of
   Manchester; University of Oxford; University of Manchester
RP D'souza, YB (通讯作者)，Manchester Royal Eye Hosp, Acad Unit, Oxford Rd, Manchester M13 9WH, Lancs, England.
EM yvonnedsouza@fsmail.net
OI Jones, Carolyn/0000-0002-0026-9494
CR Abrera-Abeleda MA, 2006, J MED GENET, V43, P582, DOI 10.1136/jmg.2005.038315
   ALPERS CE, 2005, ROBBINS COTRAN PATHO, P984
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NR 18
TC 17
Z9 17
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0085-2538
EI 1523-1755
J9 KIDNEY INT
JI Kidney Int.
PD APR
PY 2009
VL 75
IS 8
BP 824
EP 827
DI 10.1038/ki.2008.658
PG 4
WC Urology & Nephrology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Urology & Nephrology
GA 426ZQ
UT WOS:000264747900011
PM 19177159
OA Bronze
DA 2022-11-30
ER

PT J
AU Tarita-Nistor, L
   Gonzalez, EG
   Markowitz, SN
   Steinbach, MJ
AF Tarita-Nistor, Luminita
   Gonzalez, Esther G.
   Markowitz, Samuel N.
   Steinbach, Martin J.
TI Fixation characteristics of patients with macular degeneration recorded
   with the MP-1 microperimeter
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
ID PREFERRED RETINAL LOCI; SCANNING LASER OPHTHALMOSCOPE; CENTRAL SCOTOMAS;
   DISEASE; AGE; LOCATION; FOVEA; STABILITY
AB Purpose: The authors examined the fixation stability patterns of people with age-related macular degeneration (AMD) using the MP-1 microperimeter and describe a method to bypass some calibration artifacts that can influence the fixation results.
   Method: The preferred retinal locus (PRL) and fixation patterns of 37 eyes with AMD and the fovea's location relative to the middle of the optic disc of 10 experienced controls were measured. For the patients, fixation characteristics such as the former fovea's location, PRL distance, and fixation stability were analyzed.
   Results: For the controls, the mean foveal distance temporal to the middle of the optic disc was 15.5 deg +/- 0.86 deg horizontally and -1.33 deg +/- 0.71 deg vertically. Thirty-one out of 37 PRLs occurred in the upper and right quadrants of the retina. There were significant positive correlations between fixation stability and PRL distance from the former fovea. Time since diagnosis and acuity also showed positive correlations with fixation stability and PRL distance from the fovea.
   Conclusions: The authors recommend that fixation stability recorded with the MP-1 be analyzed based on the raw data. Most of the fixation parameters obtained agree with those reported in the literature, if proper calibration is used.
C1 [Tarita-Nistor, Luminita; Gonzalez, Esther G.; Steinbach, Martin J.] Toronto Western Hosp, Toronto Western Res Inst, Vis Sci Res Program, Toronto, ON M5T 2S8, Canada.
   [Tarita-Nistor, Luminita; Gonzalez, Esther G.; Steinbach, Martin J.] York Univ, Ctr Vis Res, Toronto, ON M3J 2R7, Canada.
   [Gonzalez, Esther G.; Markowitz, Samuel N.; Steinbach, Martin J.] Univ Toronto, Dept Ophthalmol, Toronto, ON, Canada.
C3 University of Toronto; University Toronto Affiliates; University Health
   Network Toronto; York University - Canada; University of Toronto
RP Steinbach, MJ (通讯作者)，Toronto Western Hosp, Toronto Western Res Inst, Vis Sci Res Program, 399 Bathurst St,MP 6-302, Toronto, ON M5T 2S8, Canada.
EM mjs@yorku.ca
CR Crossland MD, 2002, OPTOMETRY VISION SCI, V79, P735, DOI 10.1097/00006324-200211000-00011
   Crossland MD, 2005, OPHTHALMOLOGY, V112, P1579, DOI 10.1016/j.ophtha.2005.03.027
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   Fine EM, 1999, VISION RES, V39, P1039, DOI 10.1016/S0042-6989(98)00208-9
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NR 17
TC 92
Z9 105
U1 1
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 JAN
PY 2008
VL 28
IS 1
BP 125
EP 133
DI 10.1097/IAE.0b013e3180ed4571
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 251JT
UT WOS:000252370000016
PM 18185148
DA 2022-11-30
ER

PT J
AU Misiuk-Hojlo, M
   Krzyzanowska-Berkowska, P
   Hill-Bator, A
AF Misiuk-Hojlo, Marta
   Krzyzanowska-Berkowska, Patrycja
   Hill-Bator, Aneta
TI Therapeutic application of lasers in ophthalmology
SO ADVANCES IN CLINICAL AND EXPERIMENTAL MEDICINE
LA English
DT Review
DE laser; eye; treatment
ID TERM-FOLLOW-UP; PERIPHERAL IRIDOPLASTY; MANAGEMENT
AB Lasers have found application in diverse branches of medicine. In ophthalmology, laser technology has various therapeutic and diagnostic applications. The purpose of this article is to review the major therapeutic applications of lasers in different eye disorders. The effects of lasers on biological tissues and different laser techniques as well as the indications for laser therapy in various parts of the eye are discussed. Lasers are used to treat glaucoma and many vascular disorders of the retina. Laser treatment may be useful in preventing the development of neovascularization in diabetic retinopathy, BRVO, or CRVO. Laser techniques are also available for the treatment of the exudative form of age-related macular degeneration (AMD) and some malignant and benign intraocular tumors and in retina abnormalities which predispose to rhegmatogenous retinal detachment. Corneal laser surgery is the most frequently applied laser procedure in ophthalmology. PRK, LASIK, and LASEK are used to correct errors in vision such as myopia, hyperopia, and astigmatism. Laser photocoagulation is also helpful in cataract surgery. Nowadays, lasers have become so universal that it is difficult to imagine ophthalmology without them. We are still witnessing rapid advances in the development of laser techniques, especially in plastic surgery, cataract extraction, and ocular imaging (Adv Clin Exp Med 2007, 16, 6, 801-805).
C1 [Misiuk-Hojlo, Marta; Krzyzanowska-Berkowska, Patrycja; Hill-Bator, Aneta] Silesian Piasts Univ Med, Dept Ophthalmol, PL-50368 Wroclaw, Poland.
C3 Wroclaw Medical University
RP Misiuk-Hojlo, M (通讯作者)，Silesian Piasts Univ Med, Dept Ophthalmol, Chalubinskiego 2A, PL-50368 Wroclaw, Poland.
EM misiuk55@wp.pl
OI Misiuk - Hojlo, Marta/0000-0002-4020-3203
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NR 20
TC 2
Z9 2
U1 0
U2 5
PU WROCLAW MEDICAL UNIV
PI WROCLAW
PA UL K MARCINKOWSKIEGO 2-6, WROCLAW, 50-368, POLAND
SN 1899-5276
EI 2451-2680
J9 ADV CLIN EXP MED
JI Adv. Clin. Exp. Med.
PY 2007
VL 16
IS 6
BP 801
EP 805
PG 5
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA 309LF
UT WOS:000256461200012
DA 2022-11-30
ER

PT J
AU Ruamviboonsuk, V
   Grzybowski, A
AF Ruamviboonsuk, Varis
   Grzybowski, Andrzej
TI The Roles of Vitamins in Diabetic Retinopathy: A Narrative Review
SO JOURNAL OF CLINICAL MEDICINE
LA English
DT Review
DE vitamins; nutrients; dietary supplements; diabetic retinopathy
ID D DEFICIENCY; OXIDATIVE STRESS; D INSUFFICIENCY; SERUM-LEVELS;
   HOMOCYSTEINE; SUPPLEMENTS; PREVALENCE; PREVENTION; MORTALITY; MECHANISM
AB There have been attempts to evaluate the roles of vitamins for the prevention or treatment of eye conditions, such as glaucoma, age-related macular degeneration, and diabetic retinopathy (DR). Regarding DR, two main groups of studies can be identified. The first group focuses on the association between serum levels of an individual vitamin and DR. Many studies have found that lower serum levels of vitamins, particularly vitamin D, are significantly associated with the development, or severity, of DR, while some studies have not supported this trend. The second group evaluates dietary vitamin intakes and DR. A small, randomized placebo-controlled trial did not show any benefit of vitamin E intake on improving the area of retinal hemorrhage or diabetic macular edema at 12 months. A pilot study of patients with mild-to-moderate non-proliferative DR received tablets of combined vitamins B6, B9, and B12 for 6 months and significant improvement in retinal sensitivity and retinal thickness resulted. Two large prospective cohorts showed that high dietary intake of vitamin B6, and fruit rich in vitamin C and E, could significantly lower the risk of DR by 50% after an eight-year follow-up. Properly designed, randomized controlled trials are needed to support the results.
C1 [Ruamviboonsuk, Varis] Chulalongkorn Univ, Fac Med, Dept Biochem, Bangkok 10330, Thailand.
   [Grzybowski, Andrzej] Univ Warmia & Mazury, Dept Ophthalmol, PL-10719 Olsztyn, Poland.
   [Grzybowski, Andrzej] Fdn Ophthalmol Dev, Inst Res Ophthalmol, PL-61166 Poznan, Poland.
C3 Chulalongkorn University; University of Warmia & Mazury
RP Grzybowski, A (通讯作者)，Univ Warmia & Mazury, Dept Ophthalmol, PL-10719 Olsztyn, Poland.; Grzybowski, A (通讯作者)，Fdn Ophthalmol Dev, Inst Res Ophthalmol, PL-61166 Poznan, Poland.
EM ae.grzybowski@gmail.com
OI Grzybowski, Andrzej/0000-0002-3724-2391
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NR 86
TC 0
Z9 0
U1 0
U2 0
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2077-0383
J9 J CLIN MED
JI J. Clin. Med.
PD NOV
PY 2022
VL 11
IS 21
AR 6490
DI 10.3390/jcm11216490
PG 18
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 6E1IM
UT WOS:000883138100001
PM 36362717
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Yang, YS
   Dunbar, H
AF Yang, Yesa
   Dunbar, Hannah
TI Clinical Perspectives and Trends: Microperimetry as a Trial Endpoint in
   Retinal Disease
SO OPHTHALMOLOGICA
LA English
DT Review
DE Microperimetry; Fundus-related perimetry; Fundus-automated perimetry;
   Endpoints; Outcome measures
ID DIABETIC MACULAR EDEMA; TEST-RETEST VARIABILITY; CENTRAL SEROUS
   CHORIORETINOPATHY; OPTICAL COHERENCE TOMOGRAPHY; LEBER CONGENITAL
   AMAUROSIS; VEGF TRAP-EYE; TOPICAL ISOPROPYL UNOPROSTONE;
   FUNDUS-CONTROLLED PERIMETRY; LUMINANCE VISUAL-ACUITY; GENE-THERAPY
AB Endpoint development trials are underway across the spectrum of retinal disease. New validated endpoints are urgently required for the assessment of emerging gene therapies and in preparation for the arrival of novel therapeutics targeting the early stages of common sight-threatening conditions such as age-related macular degeneration and diabetic macular oedema. Visual function measures are likely to be key candidates in this search. Over the last 2 decades, microperimetry has been used extensively to characterise functional vision in a wide range of retinal conditions, often detecting subtle defects in retinal sensitivity that precede visual acuity loss and tracking disease progression over relatively short periods of time. Given these appealing features, microperimetry has already been adopted as an endpoint in interventional studies, including multicentre trials, on a modest scale. A review of its use to date shows a concurrent lack of consensus in test strategy and a wealth of innovative disease and treatment-specific metrics which may show promise as clinical trial endpoints. There are practical considerations to consider for its use, but these have not held back its popularity and it remains a widely used psychophysical test in research. Endpoint development trials will undoubtedly be key in understanding the validity of microperimetry as a clinical trial endpoint, but existing signs are promising.
C1 [Yang, Yesa; Dunbar, Hannah] UCL, UCL Inst Ophthalmol, London, England.
   [Yang, Yesa; Dunbar, Hannah] Moorfields Eye Hosp NHS Fdn Trust, London, England.
C3 University of London; University College London; University of London;
   University College London; Moorfields Eye Hospital NHS Foundation Trust
RP Yang, YS; Dunbar, H (通讯作者)，UCL, UCL Inst Ophthalmol, London, England.; Yang, YS; Dunbar, H (通讯作者)，Moorfields Eye Hosp NHS Fdn Trust, London, England.
EM h.dunbar@ucl.ac.uk
FU Innovative Medicines Initiative 2 Joint Undertaking [116076]; European
   Union's Horizon 2020 research and innovation programme; EFPIA
FX Y.Y.: None. H.D.: time funded from the Innovative Medicines Initiative 2
   Joint Undertaking 439 under grant agreement No. 116076. This Joint
   Undertaking receives support from the 440 European Union's Horizon 2020
   research and innovation programme and EFPIA.
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NR 215
TC 3
Z9 2
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3755
EI 1423-0267
J9 OPHTHALMOLOGICA
JI Ophthalmologica
PD NOV
PY 2021
VL 244
IS 5
BP 418
EP 450
DI 10.1159/000515148
PG 33
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA XK8CK
UT WOS:000727686300009
PM 33567434
OA Green Published, hybrid, Green Submitted
DA 2022-11-30
ER

PT J
AU Ju, L
   Wang, X
   Zhao, X
   Lu, HM
   Mahapatra, D
   Bonnington, P
   Ge, ZY
AF Ju, Lie
   Wang, Xin
   Zhao, Xin
   Lu, Huimin
   Mahapatra, Dwarikanath
   Bonnington, Paul
   Ge, Zongyuan
TI Synergic Adversarial Label Learning for Grading Retinal Diseases via
   Knowledge Distillation and Multi-Task Learning
SO IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS
LA English
DT Article
DE Retina; Task analysis; Computational modeling; Training; Knowledge
   engineering; Diabetes; Retinopathy; Deep convolutional neural networks;
   knowledge distillation; medical imaging classification; multi-task
   learning
ID DIABETIC-RETINOPATHY; AUTOMATED DETECTION; MULTIPLE TASKS
AB The need for comprehensive and automated screening methods for retinal image classification has long been recognized. Well-qualified doctors annotated images are very expensive and only a limited amount of data is available for various retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Some studies show that some retinal diseases such as DR and AMD share some common features like haemorrhages and exudation but most classification algorithms only train those disease models independently when the only single label for one image is available. Inspired by multi-task learning where additional monitoring signals from various sources is beneficial to train a robust model. We propose a method called synergic adversarial label learning (SALL) which leverages relevant retinal disease labels in both semantic and feature space as additional signals and train the model in a collaborative manner using knowledge distillation. Our experiments on DR and AMD fundus image classification task demonstrate that the proposed method can significantly improve the accuracy of the model for grading diseases by 5.91% and 3.69% respectively. In addition, we conduct additional experiments to show the effectiveness of SALL from the aspects of reliability and interpretability in the context of medical imaging application.
C1 [Ju, Lie; Bonnington, Paul; Ge, Zongyuan] Monash Univ, Clayton, Vic 3800, Australia.
   [Ju, Lie; Wang, Xin; Zhao, Xin; Ge, Zongyuan] Airdoc, Beijing 100000, Peoples R China.
   [Lu, Huimin] Kyushu Inst Technol, Dept Mech & Control Engn, Kitakyushu, Fukuoka 8048550, Japan.
   [Mahapatra, Dwarikanath] Incept Inst Artificial Intelligence, Abu Dhabi, U Arab Emirates.
C3 Monash University; Kyushu Institute of Technology
RP Ge, ZY (通讯作者)，Monash Univ, Clayton, Vic 3800, Australia.
EM julie334600@gmail.com; wangxin@airdoc.com; zhaoxin@airdoc.com;
   dr.huimin.lu@ieee.org; dwarikanath.mahapatra@inceptioniai.org;
   Paul.Bonnington@monash.edu; z.ge@outlook.com
OI Wang, Xin/0000-0002-6500-0445; Ge, Zongyuan/0000-0002-5880-8673; Lu,
   Huimin/0000-0001-9794-3221; Bonnington, Paul/0000-0002-9171-6949
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   Zoph B, 2018, PROC CVPR IEEE, P8697, DOI 10.1109/CVPR.2018.00907
NR 57
TC 6
Z9 6
U1 3
U2 11
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 OCT
PY 2021
VL 25
IS 10
BP 3709
EP 3720
DI 10.1109/JBHI.2021.3052916
PG 12
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 WC2SH
UT WOS:000704111100008
PM 33465032
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Gemayel, MC
   Bhatwadekar, AD
   Ciulla, T
AF Gemayel, Michael C.
   Bhatwadekar, Ashay D.
   Ciulla, Thomas
TI RNA therapeutics for retinal diseases
SO EXPERT OPINION ON BIOLOGICAL THERAPY
LA English
DT Review
DE Antisense oligonucleotides; inherited retinal disease; microRNA;
   noncoding RNA; RNA therapeutics; short hairpin RNA; small-interfering
   RNA; translational read-through inducing drugs
ID TRANSLATIONAL READ-THROUGH; CHOROIDAL NEOVASCULARIZATION; ANTISENSE
   OLIGONUCLEOTIDES; CYTOMEGALOVIRUS RETINITIS; DIABETIC-RETINOPATHY;
   MACULAR DEGENERATION; DOWN-REGULATION; MICRORNAS; DELIVERY; MECHANISMS
AB Introduction
   In the retina, noncoding RNA (ncRNA) plays an integral role in regulating apoptosis, inflammatory responses, visual perception, and photo-transduction, with altered levels reported in diseased states.
   Areas covered
   MicroRNA (miRNA), a class of ncRNA, regulates post-transcription gene expression through the binding of complementary sites of target messenger RNA (mRNA) with resulting translational repression. Small-interfering RNA (siRNA) is a double-stranded RNA (dsRNA) that regulates gene expression, leading to selective silencing of genes through a process called RNA interference (RNAi). Another form of RNAi involves short hairpin RNA (shRNA). In age-related macular degeneration (AMD) and diabetic retinopathy (DR), miRNA has been implicated in the regulation of angiogenesis, oxidative stress, immune response, and inflammation.
   Expert opinion
   Many RNA-based therapies in development are conveniently administered intravitreally, with the potential for pan-retinal effect. The majority of these RNA therapeutics are synthetic ncRNA's and hold promise for the treatment of AMD, DR, and inherited retinal diseases (IRDs). These RNA-based therapies include siRNA therapy with its high specificity, shRNA to 'knock down' autosomal dominant toxic gain of function-mutated genes, antisense oligonucleotides (ASOs), which can restore splicing defects, and translational read-through inducing drugs (TRIDs) to increase expression of full-length protein from genes with premature stop codons.
C1 [Gemayel, Michael C.; Bhatwadekar, Ashay D.; Ciulla, Thomas] Indiana Univ, Dept Ophthalmol, Eugene & Marilyn Glick Eye Inst, Indianapolis, IN 46202 USA.
   [Ciulla, Thomas] Clearside Biomed Inc, Preclin & Clin Dev, Alpharetta, GA USA.
   [Ciulla, Thomas] Midwest Eye Inst, Indianapolis, IN USA.
C3 Indiana University System; Indiana University-Purdue University
   Indianapolis
RP Ciulla, T (通讯作者)，Indiana Univ, Dept Ophthalmol, Eugene & Marilyn Glick Eye Inst, Indianapolis, IN 46202 USA.
EM thomasciulla@gmail.com
OI Ciulla, Thomas/0000-0001-5557-6777
FU US. Department of Health and Human Services, National Institutes of
   Health, National Eye Institute [R01 EY027779]
FX US. Department of Health and Human Services, National Institutes of
   Health, National Eye Institute (R01 EY027779) to AB.
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NR 73
TC 5
Z9 6
U1 0
U2 16
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1471-2598
EI 1744-7682
J9 EXPERT OPIN BIOL TH
JI Expert Opin. Biol. Ther.
PD MAY 4
PY 2021
VL 21
IS 5
BP 603
EP 613
DI 10.1080/14712598.2021.1856365
EA DEC 2020
PG 11
WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Research & Experimental Medicine
GA RV4XT
UT WOS:000598937500001
PM 33307874
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Porta, M
   Striglia, E
AF Porta, Massimo
   Striglia, Elio
TI Intravitreal anti-VEGF agents and cardiovascular risk
SO INTERNAL AND EMERGENCY MEDICINE
LA English
DT Review
DE Vascular endothelial growth factor; Diabetes mellitus; Diabetic
   retinopathy; Anti-VEGF agents; Cardiovascular risk
ID ENDOTHELIAL GROWTH-FACTOR; DIABETIC MACULAR EDEMA; VASCULAR-PERMEABILITY
   FACTOR; CORONARY-HEART-DISEASE; NITRIC-OXIDE SYNTHASE; CELLS SECRETE;
   RETINOPATHY; RANIBIZUMAB; BEVACIZUMAB; SAFETY
AB Antagonists of Vascular Endothelial Growth Factor (Anti-VEGF) are widely administered by intravitreal injection for the treatment of ocular pathologies such as Age-related Macular Degeneration, Diabetic Macular Edema, Proliferative Diabetic Retinopathy and occlusion of retinal vessels. Anti-VEGF agents, in particular bevacizumab, were introduced in oncology to inhibit tumor-induced angiogenesis feeding neoplastic tissues. Subsequently, other specific agents were developed for intraocular administration. Whereas systemic administration of anti-VEGF agents in oncology is burdened by increased risk of arterial hypertension and embolism, agents administered for ophthalmic indications are delivered locally into the eye globe in much smaller quantities. Nevertheless, clinical observations have raised the possibility that, even in these conditions, anti-VEGF agents may increase cardiovascular risk in patients who, being elderly and/or diabetic, are intrinsically prone to such events. This paper aims at reviewing the current knowledge on VEGF and its pharmacologic antagonists from mechanistic and side effect points of view, with specific reference to patients with sight-threatening conditions. Internists should be aware of the need to collaborate with ophthalmologists and pharmacovigilance operators to define as best as possible the risk/benefit balance of intravitreal agents in patients who might lose their sight if left untreated, or increase their risk of suffering a cardiovascular event if treated.
C1 [Porta, Massimo; Striglia, Elio] Univ Turin, Dept Med Sci, Corso AM Dogliotti 14, I-10126 Turin, Italy.
C3 University of Turin
RP Porta, M (通讯作者)，Univ Turin, Dept Med Sci, Corso AM Dogliotti 14, I-10126 Turin, Italy.
EM massimo.porta@unito.it
OI Porta, Massimo/0000-0002-3407-6017
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NR 83
TC 19
Z9 22
U1 0
U2 3
PU SPRINGER-VERLAG ITALIA SRL
PI MILAN
PA VIA DECEMBRIO, 28, MILAN, 20137, ITALY
SN 1828-0447
EI 1970-9366
J9 INTERN EMERG MED
JI Intern. Emerg. Med.
PD MAR
PY 2020
VL 15
IS 2
BP 199
EP 210
DI 10.1007/s11739-019-02253-7
PG 12
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA KT1UB
UT WOS:000518796800008
PM 31848994
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Peddada, KV
   Brown, A
   Verma, V
   Nebbioso, M
AF Peddada, Krishi V.
   Brown, A'sha
   Verma, Vivek
   Nebbioso, Marcella
TI Therapeutic potential of curcumin in major retinal pathologies
SO INTERNATIONAL OPHTHALMOLOGY
LA English
DT Review
DE Anti-inflammatory drug; Antioxidant drug; Anti-tumor drug; Curcuma
   longa; Curcumin; Retinal diseases
ID PIGMENT EPITHELIAL-CELLS; IN-SITU GEL; MACULAR DEGENERATION; OXIDATIVE
   STRESS; PROTEASE-INHIBITORS; EXPRESSION; DNA; ACTIVATION; APOPTOSIS;
   DELIVERY
AB PurposeThe retina is continually exposed to free radicals from its rich blood supply, numerous mitochondria, and photons of light which strike its surface. Most pathological processes that take place in the retina, such as inflammation, cell apoptosis, or angiogenesis, can hence involve free radicals directly or indirectly. Since inflammatory and oxidative stress pathways underlie retinal pathology, compounds that address these factors are therefore natural choices for treatment.This review articlesummarizes and provides commentary on curcumin's therapeutic potential use in ophthalmology with principal focus on retinal dosorders.MethodsCurcumin (diferuloylmethane) is a compound of the Indian spiceturmeric (Curcuma longa) that has been found to be efficacious in preventing and treating a number of inflammatory diseases and neoplastic processes. Curcumin exerts anti-inflammatory, anti-tumor, antioxidant, and VEGF inhibition properties through modulation of numerous biochemical mediators. This makes curcumin particularly effective in retinal disorders.ResultsCurcumin has found a role in slowing, and in some cases even reversing, age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa, proliferative vitreoretinopathy, and retinal cancers.ConclusionsHowever, studies on curcumin's efficacy have been limited mostly to animal studies. Moreover, the biomedical potential of curcumin is not easy to use, given its low solubility and oral bioavailabilitymore attention therefore has been given to nanoparticles and liposomes.
C1 [Peddada, Krishi V.] Drexel Univ, Dept Ophthalmol, Philadelphia, PA 19104 USA.
   [Brown, A'sha] Emory Univ, Emory Eye Ctr, Atlanta, GA 30322 USA.
   [Verma, Vivek] Univ Nebraska Med Ctr, Dept Radiat Oncol, Omaha, NE USA.
   [Nebbioso, Marcella] Sapienza Univ Rome, Dept Sense Organs, Ocular Electrophysiol Ctr, Viale Policlin 155, I-00161 Rome, Italy.
C3 Drexel University; Emory University; University of Nebraska System;
   University of Nebraska Medical Center; Sapienza University Rome
RP Nebbioso, M (通讯作者)，Sapienza Univ Rome, Dept Sense Organs, Ocular Electrophysiol Ctr, Viale Policlin 155, I-00161 Rome, Italy.
EM marcella.nebbioso@uniroma1.it
RI Nebbioso, Marcella/K-6878-2018
OI Nebbioso, Marcella/0000-0002-5512-0849
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NR 61
TC 30
Z9 30
U1 1
U2 22
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 MAR
PY 2019
VL 39
IS 3
BP 725
EP 734
DI 10.1007/s10792-018-0845-y
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HP3HS
UT WOS:000461568100030
PM 29404861
DA 2022-11-30
ER

PT J
AU Ding, Q
   Shang, JL
   Sun, YX
   Wang, X
   Liu, JX
AF Ding, Qian
   Shang, Junliang
   Sun, Yingxia
   Wang, Xuan
   Liu, Jin-Xing
TI HC-HDSD: A method of hypergraph construction and high-density subgraph
   detection for inferring high-order epistatic interactions
SO COMPUTATIONAL BIOLOGY AND CHEMISTRY
LA English
DT Article
DE Epistatic interactions; Single nucleotide polymorphisms (SNPs);
   Co-information; Hypergraph; High-density subgraph
ID GENOME-WIDE ASSOCIATION; VISUALIZATION; INFERENCE; PATTERNS; GENE
AB Detecting epistatic interactions, or nonlinear interactive effects of Single Nucleotide Polymorphisms (SNPs), has gained increasing attention in explaining the "missing heritability" of complex diseases. Though much work has been done in mapping SNPs underlying diseases, most of them constrain to 2-order epistatic interactions. In this paper, a method of hypergraph construction and high-density subgraph detection, named HC-HDSD, is proposed for detecting high-order epistatic interactions. The hypergraph is constructed by low-order epistatic interactions that identified using the normalized co-information measure and the exhaustive search. The hypergraph consists of two types of vertices: real ones representing main effects of SNPs and virtual ones denoting interactive effects of epistatic interactions. Then, both maximal clique centrality algorithm and near-clique mining algorithm are employed to detect high-density subgraphs from the constructed hypergraph. These high-density subgraphs are inferred as high-order epistatic interactions in the HC-HDSD. Experiments are performed on several simulation data sets, results of which show that HC-HDSD is promising in inferring high-order epistatic interactions while substantially reducing the computation cost. In addition, the application of HC-HDSD on a real Age-related Macular Degeneration (AMD) data set provides several new clues for the exploration of causative factors of AMD.
C1 [Ding, Qian; Shang, Junliang; Sun, Yingxia; Wang, Xuan; Liu, Jin-Xing] Qufu Normal Univ, Sch Informat Sci & Engn, Rizhao, Peoples R China.
   [Shang, Junliang] Qufu Normal Univ, Sch Stat, Qufu 273165, Peoples R China.
C3 Qufu Normal University; Qufu Normal University
RP Shang, JL (通讯作者)，Qufu Normal Univ, Sch Informat Sci & Engn, Rizhao, Peoples R China.
EM shangjunliang110@163.com
RI Liu, Jin-Xing/AAU-7257-2020
OI Liu, Jin-Xing/0000-0001-6104-2149
FU National Science Foundation of China [61502272, 61572284, 61701279,
   61702299]; China Postdoctoral Science Foundation [2018M642635]; Shandong
   Provincial Natural Science Foundation [ZR2017PF006, ZR2018MA019];
   Project of Shandong Province Higher Educational Science and Technology
   Program [J18KA373, J17KA063]
FX This work was supported by the National Science Foundation of China
   (61502272, 61572284, 61701279, 61702299), the China Postdoctoral Science
   Foundation (2018M642635), the Shandong Provincial Natural Science
   Foundation (ZR2017PF006, ZR2018MA019), the Project of Shandong Province
   Higher Educational Science and Technology Program (J18KA373, J17KA063).
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NR 45
TC 4
Z9 4
U1 0
U2 19
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1476-9271
EI 1476-928X
J9 COMPUT BIOL CHEM
JI Comput. Biol. Chem.
PD FEB
PY 2019
VL 78
BP 440
EP 447
DI 10.1016/j.compbiolchem.2018.11.031
PG 8
WC Biology; Computer Science, Interdisciplinary Applications
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Life Sciences & Biomedicine - Other Topics; Computer Science
GA HM5OL
UT WOS:000459524900045
PM 30595466
DA 2022-11-30
ER

PT J
AU Wylegala, A
   Wylegala, F
   Wylegala, E
AF Wylegala, Adam
   Wylegala, Filip
   Wylegala, Edward
TI Aflibercept Treatment Leads to Vascular Abnormalization of the Choroidal
   Neovascularization
SO JOURNAL OF HEALTHCARE ENGINEERING
LA English
DT Article
ID COHERENCE TOMOGRAPHY-ANGIOGRAPHY; EARLY RESPONSE; PLATFORM
AB Recent studies do not support the hypothesis of vascular normalization in the eyes receiving various types of intravitreous antivascular endothelial growth factor (VEGF). This retrospective study considered 57 eyes of 32 patients with vascular age-related macular degeneration (AMD) undergoing aflibercept treatment. In this study, we measured the vessel density, Horton-Strahler (HS) ramification ratio (complexity), and the length ratio in 14 eyes with choroidal neovascularization treated with 3-5 Eylea injections, 17 eyes receiving 1-2 injections, and 14 treatment-naive eyes to the use of swept source optical coherence tomography angiography (OCTA). Macular 6 x 6 mm scans were acquired using the DRI OCT Triton by a single trained technician. OCTA images were standardized, binarized, and skeletonized using ImageJ. Then, the HS analysis of the CNV was performed. Our data suggest that the vascular density significantly decreases after an anti-VEGF injection 36 and 93 versus 41 and 87 in treatment-naive patients. Moreover, CNV before the treatment and in a group with 3-5 injections was more complex than after receiving 1-2 injections. The branch length was not changed. Repeated anti-VEGF can lead to vascular abnormalization and further research is needed to confirm the results of this study.
C1 [Wylegala, Adam; Wylegala, Filip; Wylegala, Edward] Dist Railway Hosp, Dept Ophthalmol, Panewnicka 65, PL-40765 Katowice, Poland.
   [Wylegala, Adam; Wylegala, Filip; Wylegala, Edward] Med Univ Silesia, Sch Med, Div Dent Zabrze, Katowice, Poland.
C3 Medical University Silesia
RP Wylegala, A (通讯作者)，Dist Railway Hosp, Dept Ophthalmol, Panewnicka 65, PL-40765 Katowice, Poland.; Wylegala, A (通讯作者)，Med Univ Silesia, Sch Med, Div Dent Zabrze, Katowice, Poland.
EM adam.wylegala@gmail.com
RI Wylęgała, Edward Aleksander/AGL-6056-2022; Wylęgała, Adam/AAK-5951-2020;
   Wylegala, Edward/AAD-3961-2019
OI Wylęgała, Edward Aleksander/0000-0002-6707-5790; Wylegala,
   Adam/0000-0001-7295-4936
FU National Center for Research and Development
   [STRATEGMED1/234261/2/NCBR/2014]
FX This work was supported by the National Center for Research and
   Development Grant no. STRATEGMED1/234261/2/NCBR/2014. The authors
   express their sincere gratitude to Professor Robert Koprowski, MSc, PhD,
   Medical University of Silesia, who provided insight and expertise that
   significantly helped in the research.
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NR 16
TC 11
Z9 11
U1 0
U2 0
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 2040-2295
EI 2040-2309
J9 J HEALTHC ENG
JI J. Healthc. Eng.
PY 2018
VL 2018
AR 8595278
DI 10.1155/2018/8595278
PG 5
WC Health Care Sciences & Services
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Health Care Sciences & Services
GA GD7DR
UT WOS:000430670500001
PM 29850003
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Stanton, CM
   Borooah, S
   Drake, C
   Marsh, JA
   Campbell, S
   Lennon, A
   Soares, DC
   Vallabh, NA
   Sahni, J
   Cideciyan, AV
   Dhillon, B
   Vitart, V
   Jacobson, SG
   Wright, AF
   Hayward, C
AF Stanton, Chloe M.
   Borooah, Shyamanga
   Drake, Camilla
   Marsh, Joseph A.
   Campbell, Susan
   Lennon, Alan
   Soares, Dinesh C.
   Vallabh, Neeru A.
   Sahni, Jayashree
   Cideciyan, Artur V.
   Dhillon, Baljean
   Vitart, Veronique
   Jacobson, Samuel G.
   Wright, Alan F.
   Hayward, Caroline
TI Novel pathogenic mutations in C1QTNF5 support a dominant negative
   disease mechanism in late-onset retinal degeneration
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MFRP GENE MUTATION; MACULAR DEGENERATION; RETINITIS-PIGMENTOSA; MISSENSE
   MUTATIONS; PROTEIN COMPLEXES; THERAPY; AGE; FOVEOSCHISIS; EXPRESSION;
   EPITHELIUM
AB Late-onset retinal degeneration (L-ORD) is a rare autosomal dominant retinal dystrophy, characterised by extensive sub-retinal pigment epithelium (RPE) deposits, RPE atrophy, choroidal neovascularisation and photoreceptor cell death associated with severe visual loss. L-ORD shows striking phenotypic similarities to age-related macular degeneration (AMD), a common and genetically complex disorder, which can lead to misdiagnosis in the early stages. To date, a single missense mutation (S163R) in the C1QTNF5 gene, encoding C1q And Tumor Necrosis Factor Related Protein 5 (C1QTNF5) has been shown to cause L-ORD in a subset of affected families. Here, we describe the identification and characterisation of three novel pathogenic mutations in C1QTNF5 in order to elucidate disease mechanisms. In silico and in vitro characterisation show that these mutations perturb protein folding, assembly or polarity of secretion of C1QTNF5 and, importantly, all appear to destabilise the wildtype protein in co-transfection experiments in a human RPE cell line. This suggests that the heterozygous mutations in L-ORD show a dominant negative, rather than a haploinsufficient, disease mechanism. The function of C1QTNF5 remains unclear but this new insight into the pathogenetic basis of L-ORD has implications for future therapeutic strategies such as gene augmentation therapy.
C1 [Stanton, Chloe M.; Drake, Camilla; Marsh, Joseph A.; Campbell, Susan; Lennon, Alan; Soares, Dinesh C.; Vitart, Veronique; Wright, Alan F.; Hayward, Caroline] Univ Edinburgh, MRC, Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
   [Borooah, Shyamanga] Univ Edinburgh, MRC, Ctr Regenerat Med, Edinburgh, Midlothian, Scotland.
   [Borooah, Shyamanga; Dhillon, Baljean] Princess Alexandra Eye Pavil, Edinburgh, Midlothian, Scotland.
   [Vallabh, Neeru A.] Royal Liverpool Hosp, St Pauls Eye Unit, Liverpool, Merseyside, England.
   [Vallabh, Neeru A.; Sahni, Jayashree] Univ Liverpool, Dept Eye & Vis Sci, Liverpool, Merseyside, England.
   [Sahni, Jayashree] F Hoffmann La Roche Ltd, Roche Innovat Ctr Basel, Roche Pharma Res & Early Dev, Basel, Switzerland.
   [Cideciyan, Artur V.; Jacobson, Samuel G.] Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA.
   [Dhillon, Baljean] Univ Edinburgh, Sch Clin Sci, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland.
C3 University of Edinburgh; University of Edinburgh; Royal Liverpool &
   Broadgreen University Hospitals NHS Trust; Royal Liverpool University
   Hospital; University of Liverpool; Roche Holding; University of
   Pennsylvania; Pennsylvania Medicine; University of Edinburgh
RP Stanton, CM (通讯作者)，Univ Edinburgh, MRC, Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
EM chloe.stanton@igmm.ed.ac.uk
RI Borooah, Shyamanga/AAM-6581-2021; Cideciyan, Artur V/A-1075-2007;
   Vallabh, Neeru/AAU-5130-2020; Soares, Dinesh/A-4425-2012
OI Cideciyan, Artur V/0000-0002-2018-0905; Vallabh,
   Neeru/0000-0002-0109-4112; Soares, Dinesh/0000-0001-7557-0495; Marsh,
   Joseph/0000-0003-4132-0628; Vitart, Veronique/0000-0002-4991-3797
FU Medical Research Council at the MRC Human Genetics Unit, Edinburgh;
   Lothian Health Foundation; Macula Vision Research Foundation; Wellcome
   Trust STMTI Clinical Research Training Fellowship [R42141]; Medical
   Research Council Career Development Award [MR/M02122X/1]; MRC
   [MC_PC_U127561128, MC_U127584475, MR/M02122X/1] Funding Source: UKRI;
   Medical Research Council [MC_PC_U127584475, MC_U127584475, MR/M02122X/1,
   MC_PC_U127561128] Funding Source: researchfish
FX The authors thank the patients and their families for participating in
   this study. We also thank the medical photography department at
   Liverpool, Neil Parry from the dark adaptometry team in Manchester who
   worked with S.B. to obtain clinical images, and Jonathan Marten who
   helped with figure preparation. This work was supported by the Medical
   Research Council at the MRC Human Genetics Unit, Edinburgh and Lothian
   Health Foundation support for studies into L-ORD and AMD, and the Macula
   Vision Research Foundation. SB was supported by a Wellcome Trust STMTI
   Clinical Research Training Fellowship (Grant number R42141). J.A.M is
   supported by a Medical Research Council Career Development Award
   (MR/M02122X/1). The funders had no role in designing or performing the
   study, or in preparation for publication.
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NR 34
TC 18
Z9 18
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD SEP 22
PY 2017
VL 7
AR 12147
DI 10.1038/s41598-017-11898-3
PG 15
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA FH8HO
UT WOS:000411434900013
PM 28939808
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Liu, HJ
   Liu, WW
   Zhou, X
   Long, CD
   Kuang, XL
   Hu, J
   Tang, Y
   Liu, LY
   He, J
   Huang, ZX
   Fan, YT
   Jin, GR
   Zhang, QJ
   Shen, HX
AF Liu, Huijun
   Liu, Weiwei
   Zhou, Xin
   Long, Chongde
   Kuang, Xielan
   Hu, Jie
   Tang, Yan
   Liu, Lanying
   He, Jia
   Huang, Zixin
   Fan, Yuting
   Jin, Guorong
   Zhang, Qingjiong
   Shen, Huangxuan
TI Protective effect of lutein on ARPE-19 cells upon H2O2-induced G(2)/M
   arrest
SO MOLECULAR MEDICINE REPORTS
LA English
DT Article
DE age-related macular degeneration; oxidative stress; lutein; retinal
   pigment epithelium; G(2)/M arrest
ID PIGMENT EPITHELIAL-CELLS; MACULAR DEGENERATION; OXIDATIVE STRESS; CYCLE
   ARREST; DNA-DAMAGE; VITAMIN-E; ZEAXANTHIN; EYE; CAROTENOIDS; EXPRESSION
AB Oxidative damage is a key factor for the pathogenesis of age-related macular degeneration (AMD), therefore, anti-oxidative stress is a valuable method for the prevention or treatment of AMD. The aim of the present study was to reveal the protective mechanism of lutein on retinal pigment epithelium (RPE) cells subjected to oxidative stress. Acute retinal pigment epithelial 19 (ARPE-19) cells were exposed to oxidative stress induced by H2O2 following lutein pretreatment. The activities of caspases, level of intracellular reactive oxygen species (ROS) and cell cycle were analyzed using flow cytometry. The expression levels of cell cycle regulatory proteins and inflammation-associated genes were detected using western blot and reverse transcription-polymerase chain reaction analyses, respectively. The data showed that oxidative stress reduced cell viability, and increased total apoptosis and ROS generation, however, lutein prevented cells from oxidative stress-induced damage. In addition, oxidative damage triggered G(2)/M phase arrest of the ARPE-19 cells, which was reversed by lutein in a concentration-dependent manner, through the activation of cyclin-dependent kinase 1 and cell division cycle 25C, and degradation of cyclin B1. These results demonstrated that lutein may be an effective antioxidant, which can be applied in the prevention of AMD, or other age-related diseases associated with oxidative damage.
C1 [Liu, Huijun; Liu, Weiwei; Zhou, Xin; Long, Chongde; Kuang, Xielan; Hu, Jie; Tang, Yan; Liu, Lanying; He, Jia; Huang, Zixin; Fan, Yuting; Jin, Guorong; Zhang, Qingjiong; Shen, Huangxuan] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Guangdong, Peoples R China.
   [Kuang, Xielan; Shen, Huangxuan] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Biobank Eye, 54 South Xianlie Rd, Guangzhou 510060, Guangdong, Peoples R China.
C3 Sun Yat Sen University; Sun Yat Sen University
RP Shen, HX (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Biobank Eye, 54 South Xianlie Rd, Guangzhou 510060, Guangdong, Peoples R China.
EM shenhx@mail.sysu.edu.cn
RI Zhang, Qingjiong/AAR-6331-2021
OI Zhang, Qingjiong/0000-0001-7508-848X; Zhou, Xin/0000-0002-0480-3068
FU National Natural Science Foundation of China [81270914, 81670874]
FX The present study was supported by the National Natural Science
   Foundation of China (grant nos. 81270914 and 81670874) to H.X.S.
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NR 25
TC 36
Z9 37
U1 1
U2 19
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1791-2997
EI 1791-3004
J9 MOL MED REP
JI Mol. Med. Rep.
PD AUG
PY 2017
VL 16
IS 2
BP 2069
EP 2074
DI 10.3892/mmr.2017.6838
PG 6
WC Oncology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Oncology; Research & Experimental Medicine
GA EZ9VX
UT WOS:000405079300139
PM 28656238
OA Bronze
DA 2022-11-30
ER

PT J
AU Ravera, V
   Bottoni, F
   Giani, A
   Cigada, M
   Staurenghi, G
AF Ravera, Vittoria
   Bottoni, Ferdinando
   Giani, Andrea
   Cigada, Mario
   Staurenghi, Giovanni
TI RETINAL ANGIOMATOUS PROLIFERATION DIAGNOSIS A Multiimaging Approach
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE AMD; multiimaging; RAP
ID OPTICAL COHERENCE TOMOGRAPHY; RETICULAR PSEUDODRUSEN; TYPE-3
   NEOVASCULARIZATION; MACULAR DEGENERATION; GEOGRAPHIC-ATROPHY;
   NATURAL-HISTORY; PREVALENCE; RISK; ASSOCIATION; ANGIOGRAPHY
AB Purpose: To identify signs occurring more frequently in retinal angiomatous proliferation (RAP) lesions compared with other types of choroidal neovascularization (CNV) in age-related macular degeneration.
   Methods: In this cross-sectional retrospective study, 30 patients were evaluated. These signs were correlated with the type of CNV: shunting of blood flow to the lesion by fluorescein angiography, late leakage by indocyanine green angiography, intraretinal cysts and retinal pigmented epithelium interruption along the retinal pigmented epithelium detachment with a hyperreflective oval area by spectral domain optical coherence tomography, and presence of reticular pseudodrusen by infrared light.
   Results: Shunting of blood flow was found in 56% of RAP, whereas it was absent in 100% of other CNVs. Late leakage in indocyanine green angiography occurred in all RAP cases, while it was found in 7% of other CNVs. Intraretinal cysts were detected in 100% of RAP cases and in 14% of other CNVs. Retinal pigmented epithelium interruption along the retinal pigmented epithelium detachment was evident in 93% of RAP cases and in 15% of other CNVs. Reticular pseudodrusen were present in 87% of RAP cases and in 21% of other CNVs.
   Conclusion: All the signs investigated were strongly associated to RAP lesions. A multimodal imaging approach may help differentiating subtypes of neovascularization.
C1 [Ravera, Vittoria; Bottoni, Ferdinando; Giani, Andrea; Cigada, Mario; Staurenghi, Giovanni] Univ Milan, Luigi Sacco Hosp, Dept Clin Sci Luigi Sacco, Eye Clin, Via GB Grassi 74, I-20157 Milan, Italy.
C3 University of Milan; Luigi Sacco Hospital
RP Staurenghi, G (通讯作者)，Univ Milan, Luigi Sacco Hosp, Dept Clin Sci Luigi Sacco, Eye Clin, Via GB Grassi 74, I-20157 Milan, Italy.
EM giovanni.staurenghi@unimi.it
RI Staurenghi, Giovanni/K-4388-2017; Giani, Andrea/L-5926-2017
OI Staurenghi, Giovanni/0000-0002-2299-5251; Giani,
   Andrea/0000-0003-0682-1945
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NR 28
TC 21
Z9 23
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 DEC
PY 2016
VL 36
IS 12
BP 2274
EP 2281
DI 10.1097/IAE.0000000000001152
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA ED6DB
UT WOS:000388944100004
PM 27870798
DA 2022-11-30
ER

PT J
AU Subhani, S
   Vavilala, DT
   Mukherji, M
AF Subhani, Saima
   Vavilala, Divya Teja
   Mukherji, Mridul
TI HIF inhibitors for ischemic retinopathies and cancers: options beyond
   anti-VEGF therapies
SO ANGIOGENESIS
LA English
DT Review
DE Ocular neovascularization; Metastatic cancer; Hypoxia inducible factor;
   VEGF; Honokiol; HIF inhibitors
ID ENDOTHELIAL GROWTH-FACTOR; INDUCIBLE FACTOR-I; EXPERIMENTAL CHOROIDAL
   NEOVASCULARIZATION; 1-METHYLPROPYL 2-IMIDAZOLYL DISULFIDE;
   VASCULAR-PERMEABILITY FACTOR; FIH-MEDIATED REPRESSION;
   CARDIAC-GLYCOSIDES; INTRAVITREAL INJECTION; RETINAL NEOVASCULARIZATION;
   OCULAR NEOVASCULARIZATION
AB Aberrant activation of the hypoxia inducible factor (HIF) pathway causing overexpression of angiogenic genes, like vascular endothelial growth factor (VEGF), is one of the underlying causes of ocular neovascularization (NV) and metastatic cancer. Consistently, along with surgical interventions, a number of anti-VEGF agents have been approved by FDA for the treatment of ocular neovascular diseases. These anti-VEGF agents, like ranibizumab/lucentis, have revolutionized the treatment in the past decade. However, substantial vision improvement is observed only in a subset of age-related macular degeneration patients receiving ranibizumab. Further, all current therapies are associated with limitations and side effects. For example, surgeries cause tissue destruction and inflammation while anti-VEGF therapies are expensive, require repeated administration, and offer temporary relief from vascular leakage. These factors impose significant cost and treatment burdens to both the patient and society. With an aging population in most western countries with a continually increasing number of patients on lifelong treatment for these retinal diseases, the focus of ocular drug development for neovascular diseases will be to improve efficacy while reducing treatment costs. Blocking the HIF pathway, a major regulator of ocular NV and cancer, offers an appealing therapeutic strategy. Therefore, this review summarizes HIF inhibitors that have been recently evaluated for the treatment of different cancers and ischemic retinopathies.
C1 [Subhani, Saima; Vavilala, Divya Teja; Mukherji, Mridul] Univ Missouri, Sch Pharm, Div Pharmaceut Sci, Kansas City, MO 64110 USA.
C3 University of Missouri System; University of Missouri Kansas City
RP Mukherji, M (通讯作者)，Univ Missouri, Sch Pharm, Div Pharmaceut Sci, Kansas City, MO 64110 USA.
EM mukherjim@umkc.edu
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NR 191
TC 17
Z9 21
U1 3
U2 21
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0969-6970
EI 1573-7209
J9 ANGIOGENESIS
JI Angiogenesis
PD JUL
PY 2016
VL 19
IS 3
BP 257
EP 273
DI 10.1007/s10456-016-9510-0
PG 17
WC Peripheral Vascular Disease
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cardiovascular System & Cardiology
GA DQ5BO
UT WOS:000379219600001
PM 27146677
DA 2022-11-30
ER

PT J
AU Khanani, AM
   Cohen, GL
   Zawadzki, R
AF Khanani, Arshad M.
   Cohen, Gregory L.
   Zawadzki, Rezi
TI A Prospective Masked Clinical Assessment of Inflammation After
   Intravitreal Injection of Ranibizumab or Aflibercept
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID STANDARDIZATION; VERTEPORFIN
AB Purpose: To compare anterior chamber and vitreous inflammation after intravitreal injection of ranibizumab or aflibercept.
   Methods: This was a prospective, open label, nonrandomized phase 4 clinical study. One hundred patients with choroidal neovascularization due to age-related macular degeneration received intravitreal aflibercept (N = 53) or ranibizumab (N = 47). Medication use was balanced by gender, injected eye, and lens status (phakic vs. pseudophakic). An examiner masked to medication graded anterior chamber and vitreous inflammation 1-2 and 5-7 days after injection according to the Standardization of Uveitis Nomenclature grading scheme.
   Results: Mean patient age was 78.6 years. Maximum anterior chamber reaction of 0.5+ was seen at the first postinjection examination in 2% of eyes receiving ranibizumab and in 19% of eyes receiving aflibercept (Fisher's exact test 2 sided, P = 0.0091); vitreous reaction was minimal and infrequent in both groups and the difference was not statistically significant. At 5-7 days after injection, 1 patient treated with aflibercept had residual anterior chamber inflammation of 0.5+ and no patient treated with ranibizumab had residual inflammation.
   Conclusion: Aflibercept may be associated with more anterior chamber inflammation than ranibizumab, although mild and transient. This should not be mistaken for endophthalmitis.
C1 [Khanani, Arshad M.; Cohen, Gregory L.] Sierra Eye Associates, 950 Ryland St, Reno, NV 89502 USA.
   [Zawadzki, Rezi] GISS Enterprises, San Francisco, CA USA.
RP Khanani, AM (通讯作者)，Sierra Eye Associates, 950 Ryland St, Reno, NV 89502 USA.
EM arshad.khanani@gmail.com
FU Genentech, Inc.
FX Sandra M. Brown, MD, assisted with the writing and submission of this
   article. Dr. Brown was compensated for her work by Sierra Eye
   Associates. This work was partially funded by a grant from Genentech,
   Inc. Genentech participated in study design only.
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NR 9
TC 14
Z9 15
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 MAY
PY 2016
VL 32
IS 4
BP 216
EP 218
DI 10.1089/jop.2015.0152
PG 3
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA DN9KB
UT WOS:000377397300007
PM 26938579
DA 2022-11-30
ER

PT J
AU Krishnamoorthy, V
   Cherukuri, P
   Poria, D
   Goel, M
   Dagar, S
   Dhingra, NK
AF Krishnamoorthy, Vidhyasankar
   Cherukuri, Pitchaiah
   Poria, Deepak
   Goel, Manvi
   Dagar, Sushma
   Dhingra, Narender K.
TI Retinal Remodeling: Concerns, Emerging Remedies and Future Prospects
SO FRONTIERS IN CELLULAR NEUROSCIENCE
LA English
DT Article
DE retinal degeneration; oscillatory activity; retinal prostheses; stem
   cells; optogenetics
ID LEBER CONGENITAL AMAUROSIS; RESTORES VISUAL RESPONSES; AII AMACRINE
   CELLS; GENE-THERAPY; MOUSE MODEL; GANGLION-CELLS; MULLER GLIA; BIPOLAR
   CELLS; ROYAL-COLLEGE; IMMUNOCYTOCHEMICAL LOCALIZATION
AB Deafferentation results not only in sensory loss, but also in a variety of alterations in the postsynaptic circuitry. These alterations may have detrimental impact on potential treatment strategies. Progressive loss of photoreceptors in retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration, leads to several changes in the remnant retinal circuitry. Muller glial cells undergo hypertrophy and form a glial seal. The second- and third-order retinal neurons undergo morphological, biochemical and physiological alterations. A result of these alterations is that retinal ganglion cells (RGCs), the output neurons of the retina, become hyperactive and exhibit spontaneous, oscillatory bursts of spikes. This aberrant electrical activity degrades the signal-to-noise ratio in RGC responses, and thus the quality of information they transmit to the brain. These changes in the remnant retina, collectively termed "retinal remodeling", pose challenges for genetic, cellular and bionic approaches to restore vision. It is therefore crucial to understand the nature of retinal remodeling, how it affects the ability of remnant retina to respond to novel therapeutic strategies, and how to ameliorate its effects. In this article, we discuss these topics, and suggest that the pathological state of the retinal output following photoreceptor loss is reversible, and therefore, amenable to restorative strategies.
C1 [Krishnamoorthy, Vidhyasankar] Univ Med Ctr Gottingen, Dept Ophthalmol, Gottingen, Germany.
   [Cherukuri, Pitchaiah] European Neurosci Inst Gottingen, Dev Neurobiol Lab, Gottingen, Germany.
   [Poria, Deepak; Goel, Manvi; Dhingra, Narender K.] Natl Brain Res Ctr, Manesar, Haryana, India.
   [Dagar, Sushma] Univ Dusseldorf, Inst Neuro & Sensory Physiol, Dusseldorf, Germany.
C3 University of Gottingen; Department of Biotechnology (DBT) India;
   National Brain Research Centre (NBRC); Heinrich Heine University
   Dusseldorf
RP Dhingra, NK (通讯作者)，Natl Brain Res Ctr, Manesar, Haryana, India.
EM narender.dhingra@gmail.com
RI Goel, Manvi/T-3148-2019
OI Goel, Manvi/0000-0003-2049-5605
FU National Brain Research Centre, India
FX This study was funded by National Brain Research Centre, India.
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NR 150
TC 13
Z9 15
U1 0
U2 24
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 1662-5102
J9 FRONT CELL NEUROSCI
JI Front. Cell. Neurosci.
PD FEB 17
PY 2016
VL 10
AR 38
DI 10.3389/fncel.2016.00038
PG 9
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA DD9HB
UT WOS:000370235200001
PM 26924962
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Schmidl, D
   Schmetterer, L
   Garhofer, G
   Popa-Cherecheanu, A
AF Schmidl, Doreen
   Schmetterer, Leopold
   Garhoefer, Gerhard
   Popa-Cherecheanu, Alina
TI Gender Differences in Ocular Blood Flow
SO CURRENT EYE RESEARCH
LA English
DT Review
DE Age-related macular degeneration; diabetic retinopathy; gender;
   glaucoma; ocular blood flow
ID RETINAL VEIN OCCLUSION; OPEN-ANGLE GLAUCOMA; OPTICAL COHERENCE
   TOMOGRAPHY; BLUE-MOUNTAINS-EYE; HORMONE REPLACEMENT THERAPY; AGE-RELATED
   MACULOPATHY; SYSTEMIC-LUPUS-ERYTHEMATOSUS; LASER-DOPPLER FLOWMETRY;
   NORMAL-TENSION GLAUCOMA; MACULAR DEGENERATION
AB Gender medicine has been a major focus of research in recent years. The present review focuses on gender differences in the epidemiology of the most frequent ocular diseases that have been found to be associated with impaired ocular blood flow, such as age-related macular degeneration, glaucoma and diabetic retinopathy. Data have accumulated indicating that hormones have an important role in these diseases, since there are major differences in the prevalence and incidence between men and pre-and post-menopausal women. Whether this is related to vascular factors is, however, not entirely clear. Interestingly, the current knowledge about differences in ocular vascular parameters between men and women is sparse. Although little data is available, estrogen, progesterone and testosterone are most likely important regulators of blood flow in the retina and choroid, because they are key regulators of vascular tone in other organs. Estrogen seems to play a protective role since it decreases vascular resistance in large ocular vessels. Some studies indicate that hormone therapy is beneficial for ocular vascular disease in post-menopausal women. This evidence is, however, not sufficient to give any recommendation. Generally, remarkably few data are available on the role of sex hormones on ocular blood flow regulation, a topic that requires more attention in the future.
C1 [Schmidl, Doreen; Schmetterer, Leopold; Garhoefer, Gerhard] Med Univ Vienna, Dept Clin Pharmacol, Vienna, Austria.
   [Schmetterer, Leopold] Med Univ Vienna, Ctr Med Phys & Biomed Engn, Vienna, Austria.
   [Popa-Cherecheanu, Alina] Emergency Univ Hosp, Dept Ophthalmol, Bucharest, Romania.
C3 Medical University of Vienna; Medical University of Vienna
RP Schmetterer, L (通讯作者)，Med Univ Vienna, Dept Clin Pharmacol, Wahringer Gurtel 18-20, Vienna, Austria.
EM leopold.schmetterer@meduniwien.ac.at
OI Schmidl, Doreen/0000-0001-5664-7768; Schmetterer,
   Leopold/0000-0002-7189-1707; Popa-Cherecheanu, Alina/0000-0003-4189-6571
FU Fonds zur Forderung der Wissenschaftlichen Forschung (FWF) [APP21570FW,
   APP21406FW]; Die Osterreichische Forschungsforderungsgesellschaft (FFG)
   [FA 607A0502]; Christian Doppler Laboratory for Laser Development and
   their Application in Medicine; Austrian Science Fund (FWF) [P 21570, P
   21406] Funding Source: researchfish
FX The authors report no conflicts of interest. Part of the experimental
   work mentioned in this article was supported by the following grants:
   Fonds zur Forderung der Wissenschaftlichen Forschung (FWF), Projects No.
   APP21570FW and APP21406FW, Die Osterreichische
   Forschungsforderungsgesellschaft (FFG) project FA 607A0502, Christian
   Doppler Laboratory for Laser Development and their Application in
   Medicine.
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NR 184
TC 45
Z9 46
U1 0
U2 16
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0271-3683
EI 1460-2202
J9 CURR EYE RES
JI Curr. Eye Res.
PD FEB
PY 2015
VL 40
IS 2
BP 201
EP 212
DI 10.3109/02713683.2014.906625
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AZ4TB
UT WOS:000348214800010
PM 24892919
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Zhao, L
   Ma, WX
   Fariss, RN
   Wong, WT
AF Zhao, Lian
   Ma, Wenxin
   Fariss, Robert N.
   Wong, Wai T.
TI Minocycline Attenuates Photoreceptor Degeneration in a Mouse Model of
   Subretinal Hemorrhage Microglial Inhibition as a Potential Therapeutic
   Strategy
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID TISSUE-PLASMINOGEN ACTIVATOR; CHOROIDAL NEOVASCULAR LESIONS; NF-KAPPA-B;
   INTRACEREBRAL HEMORRHAGE; MACULAR DEGENERATION; SUBMACULAR HEMORRHAGE;
   RETINAL MICROGLIA; BRAIN-INJURY; WHOLE-BLOOD; COMPLEMENT
AB Hemorrhage under the neural retina (subretinal hemorrhage) can occur in the context of age-related macular degeneration and induce subsequent photoreceptor cell death and permanent vision loss. Current treatments with the objective of removing or displacing the hemorrhage are invasive and of mixed efficacy. We created a mouse model of subretinal hemorrhage to characterize the inflammatory responses and photoreceptor degeneration that occur in the acute aftermath of hemorrhage. It was observed that microglial infiltration into the outer retina commences as early as 6 hours after hemorrhage. Inflammatory cells progressively accumulate in the outer nuclear layer concurrently with photoreceptor degeneration and apoptosis. Administration of minocycline, an inhibitor of microglial activation, decreased microglial expression of chemotactic cytokines in vitro and reduced microglial infiltration and photoreceptor cell loss after subretinal hemorrhage in vivo. Inflammatory responses and photoreceptor atrophy occurred after subretinal hemorrhage, however, the degree of response and atrophy were similar between C3-deficient and C3-sufficient mice, indicating a limited role for complement-mediated processes. Our data indicate a role for inflammatory responses in driving photoreceptor cell loss in subretinal hemorrhage, and it is proposed that microglial inhibition may be beneficial in the treatment of subretinal hemorrhage. (Am J Pathol 2011, 179:1265-1277; DOI: 10.1016/j.ajpath.2011.05.042)
C1 [Zhao, Lian; Ma, Wenxin; Wong, Wai T.] NEI, Unit Neuron Glia Interact Retinal Dis, Off Sci Director, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI)
RP Wong, WT (通讯作者)，NEI, Unit Neuron Glia Interact Retinal Dis, Off Sci Director, NIH, 6 Ctr Dr,Rm 217, Bethesda, MD 20892 USA.
EM wongw@nei.nih.gov
RI Fariss, Robert/ABI-1771-2020; Wong, Wai/B-6118-2017
OI Wong, Wai/0000-0003-0681-4016; Fariss, Robert/0000-0003-3227-7170
FU Prevention of Blindness Metropolitan Washington; National Eye Institute;
   NATIONAL EYE INSTITUTE [ZICEY000459, ZIAEY000505] Funding Source: NIH
   RePORTER
FX Supported by a grant from Prevention of Blindness Metropolitan
   Washington and by the National Eye Institute Intramural Research
   Program.
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Z9 37
U1 0
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PA STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
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VL 179
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BP 1265
EP 1277
DI 10.1016/j.ajpath.2011.05.042
PG 13
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA 865JN
UT WOS:000298307300021
PM 21763674
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Choi, DY
   Ortube, MC
   Mccannel, CA
   Sarraf, D
   Hubschman, JP
   Mccannel, TA
   Gorin, MB
AF Choi, Daniel Y.
   Ortube, Maria Carolina
   Mccannel, Colin A.
   Sarraf, David
   Hubschman, Jean-Pierre
   Mccannel, Tara A.
   Gorin, Michael B.
TI SUSTAINED ELEVATED INTRAOCULAR PRESSURES AFTER INTRAVITREAL INJECTION OF
   BEVACIZUMAB, RANIBIZUMAB, AND PEGAPTANIB
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE intravitreal injections; elevated intraocular pressure; sustained
   elevated intraocular pressure
ID MACULAR DEGENERATION; AVASTIN; SAFETY
AB Purpose: To investigate elevated intraocular pressures (IOP) (defined by a measurement >25 mmHg at a follow-up visit) after an intravitreal injection of anti-vascular endothelial growth factor agents for age-related macular degeneration.
   Methods: Retrospective review of medical records.
   Results: A total of 127 patients (155 eyes) received an intravitreal injection of antivascular endothelial growth factor agents (bevacizumab, ranibizumab, or pegaptanib) ranging from 1 to 39 injections for more than a period of 30 to 1759 days. Among this population, 12 patients (14 eyes; 9.4%) developed elevated IOP >25 mmHg. Of these, 7 patients (5.5%) developed sustained elevated IOP (IOP >25 mmHg on 2 separate visits requiring glaucoma medication or surgery), of which 8 eyes required topical medications and 1 eye underwent glaucoma surgery. Mean IOP of injected eyes receiving intravitreal injection was 15.2 +/- 2.4 mmHg, and the mean IOP was 14.9 +/- 2.6 mmHg for noninjected eyes. Among eyes that had elevated IOPs, there was no association with injection frequency, number of injections, or anti-vascular endothelial growth factor agent used.
   Conclusion: Elevated IOP, sustained or unsustained, after intravitreal injection is not uncommon. No association with patient demographics or injection history was identified in the authors' study population. RETINA 31:1028-1035, 2011
C1 [Choi, Daniel Y.; Ortube, Maria Carolina; Mccannel, Colin A.; Sarraf, David; Hubschman, Jean-Pierre; Mccannel, Tara A.; Gorin, Michael B.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles;
   University of California Los Angeles Medical Center; David Geffen School
   of Medicine at UCLA
RP Gorin, MB (通讯作者)，100 Stein Plaza,DSERC 3-310B, Los Angeles, CA 90095 USA.
EM gorin@jsei.ucla.edu
OI Hubschman, Jean-Pierre/0000-0002-8631-3467; McCannel, Colin
   Archibald/0000-0003-0774-6414
CR Adelman RA, 2010, J OCUL PHARMACOL TH, V26, P105, DOI 10.1089/jop.2009.0076
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NR 19
TC 81
Z9 85
U1 0
U2 11
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 2011
VL 31
IS 6
BP 1028
EP 1035
DI 10.1097/IAE.0b013e318217ffde
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 769JT
UT WOS:000291009400003
PM 21836409
DA 2022-11-30
ER

PT J
AU Wilkinson, JT
   Fraunfelder, FW
AF Wilkinson, Justin T.
   Fraunfelder, Frederick W.
TI Use of Herbal Medicines and Nutritional Supplements in Ocular Disorders
   An Evidence-Based Review
SO DRUGS
LA English
DT Review
ID GINKGO-BILOBA EXTRACT; AGE-RELATED CATARACT; COHERENCE TOMOGRAPHY
   FINDINGS; ANTIOXIDANT NUTRIENT INTAKE; VITAMIN-E SUPPLEMENTATION;
   LONG-TERM INCIDENCE; MACULAR DEGENERATION; DIABETIC-RETINOPATHY;
   ALTERNATIVE MEDICINE; RANDOMIZED-TRIAL
AB We sought to examine the evidence regarding the use of herbal medicines and nutritional supplements in age-related macular degeneration (AMD), cataracts, diabetic retinopathy and glaucoma, and to review the ocular adverse effects of herbal and nutritional agents of clinical importance to ophthalmologists. We performed a literature search of Ovid MEDLINE and selected websites including the American Academy of Ophthalmology (AAO), the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH) and the World Health Organization (WHO).
   There is strong evidence supporting the use of antioxidants and zinc in patients with certain forms of intermediate and advanced AMD. However, there has been growing evidence regarding potential significant adverse effects associated with the AREDS (Age-Related Eye Disease Study) formula vitamins. Current data does not support the use of antioxidants or herbal medications in the prevention or treatment of cataracts, glaucoma or diabetic retinopathy.
   It is important for providers to be aware of the benefits and the significant potential adverse effects that have been associated with nutritional supplements and herbal medications, and to properly inform their patients when making decisions about supplementation. Further rigorous evaluation of nutritional supplements and herbal medicines in the treatment of eye disease is needed to determine their safety and efficacy.
C1 [Wilkinson, Justin T.; Fraunfelder, Frederick W.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97239 USA.
   [Fraunfelder, Frederick W.] Casey Eye Inst, Natl Registry Drug Induced Ocular Side Effects, Portland, OR USA.
C3 Oregon Health & Science University
RP Fraunfelder, FW (通讯作者)，Oregon Hlth & Sci Univ, Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA.
EM eyedrug@ohsu.edu
FU Research to Prevent Blindness, New York, NY, USA
FX This study was supported in part by an unrestricted grant from Research
   to Prevent Blindness, New York, NY, USA. The authors have no proprietary
   interest in these materials, or other conflicts of interest that are
   directly relevant to the content of this review.
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NR 100
TC 19
Z9 20
U1 0
U2 28
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 2011
VL 71
IS 18
BP 2421
EP 2434
DI 10.2165/11596840-000000000-00000
PG 14
WC Pharmacology & Pharmacy; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy; Toxicology
GA 872UM
UT WOS:000298835200005
PM 22141385
DA 2022-11-30
ER

PT J
AU Khar, RK
   Jain, GK
   Warsi, MH
   Mallick, N
   Akhter, S
   Pathan, SA
   Ahmad, FJ
AF Khar, R. K.
   Jain, G. K.
   Warsi, M. H.
   Mallick, N.
   Akhter, S.
   Pathan, S. A.
   Ahmad, F. J.
TI Nano-vectors for the Ocular Delivery of Nucleic Acid-based Therapeutics
SO INDIAN JOURNAL OF PHARMACEUTICAL SCIENCES
LA English
DT Review
DE Dendrimers; liposomes; nucleic acid; nano-vectors; nanoparticles; ocular
   delivery
ID NONVIRAL GENE-TRANSFER; PIGMENT EPITHELIAL-CELLS; COMPACTED DNA
   NANOPARTICLES; ANTI-VEGF APTAMER; ANTISENSE OLIGONUCLEOTIDES;
   DRUG-DELIVERY; CHOROIDAL NEOVASCULARIZATION; CATIONIC LIPOSOMES;
   MEDIATED DELIVERY; EYE DROPS
AB Nucleic acid-based therapeutics have gained a lot of interest for the treatment of diverse ophthalmic pathologies. The first to enter in clinic has been an oligonucleotide, Vitravene(R) for the treatment of cytomegalovirus infection. More recently, research on aptamers for the treatment of age related macular degeneration has led to the development of Macugen(R). Despite intense potential, effective ocular delivery of nucleic acids is a major challenge since therapeutic targets for nucleic acid-based drugs are mainly located in the posterior eye segment, requiring repeated invasive administration. Of late, nanotechnology-based nano-vectors have been developed in order to overcome the drawbacks of viral and other non-viral vectors. The diversity of nano-vectors allows for ease of use, flexibility in application, low-cost of production, higher transfection efficiency and enhanced genomic safety. Using nano-vector strategies, nucleic acids can be delivered either encapsulated or complexed with cationic lipids, polymers or peptides forming sustained release systems, which can be tailored according to the ocular tissue being targeted. The present review focuses on developments and advances in various nano-vectors for the ocular delivery of nucleic acid-based therapeutics, the barriers that such delivery systems face and methods to overcome them.
C1 [Khar, R. K.; Jain, G. K.; Warsi, M. H.; Mallick, N.; Akhter, S.; Pathan, S. A.; Ahmad, F. J.] Jamia Hamdard, Fac Pharm, Dept Pharmaceut, New Delhi 110062, India.
C3 Jamia Hamdard University
RP Khar, RK (通讯作者)，Jamia Hamdard, Fac Pharm, Dept Pharmaceut, New Delhi 110062, India.
EM roopkhar@hotmail.com
RI Warsi, Musarrat/AAN-6095-2021; du, zhao jiang/F-6229-2011
OI Warsi, Musarrat/0000-0002-9071-8889; Jain, Gaurav
   kumar/0000-0003-1719-238X; Ahmad, Farhan/0000-0002-0740-8573; Akhtar,
   Sohail/0000-0002-7591-7089
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NR 80
TC 18
Z9 22
U1 2
U2 47
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 0250-474X
EI 1998-3743
J9 INDIAN J PHARM SCI
JI Indian J. Pharm. Sci.
PD NOV-DEC
PY 2010
VL 72
IS 6
BP 675
EP 688
DI 10.4103/0250-474X.84575
PG 14
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 819VP
UT WOS:000294860000001
PM 21969738
OA Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Sivaprasad, S
   Bailey, TA
   Chong, VNH
AF Sivaprasad, S
   Bailey, TA
   Chong, VNH
TI Bruch's membrane and the vascular intima: is there a common basis for
   age-related changes and disease?
SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Bruch's membrane; vascular intima; age-related macular degeneration;
   atherosclerosis
ID CHOROIDAL NEOVASCULAR MEMBRANES; RETINAL-PIGMENT EPITHELIUM;
   ELASTIN-DERIVED PEPTIDES; MACULAR DEGENERATION; EXTRACELLULAR-MATRIX;
   TISSUE INHIBITOR; DRUSEN FORMATION; ATHEROSCLEROTIC LESIONS;
   MORPHOMETRIC-ANALYSIS; AGING CHANGES
AB Several clinical and epidemiological studies have concurrently illuminated established cardiovascular risk factors in age-related macular degeneration (AMD), raising the possibility that cardiovascular disease and AMD may share a similar pathogenic process. The vascular intima and the Bruch's membrane share several age-related changes and are the seat of many common molecules. Diseases of these structures may represent parallel responses to the tissue injury induced by multiple intercalated factors such as genetic variations, oxidative stress, inappropriately directed immune response or inflammatory disease complex. However, there are marked differences in the age-related changes in these two structures. The strategic location of the Bruch's membrane between the retinal pigment epithelium and the choriocapillaris can at least partially explain the differential susceptibility of AMD to cardiovascular risk factors. Unlike the vascular wall that is exposed to changes from the endothelium, the Bruch's membrane is subject to changes from both the endothelium (choriocapillaris) and epithelium (retinal pigment epithelium). Moreover, although both the vascular wall and Bruch's membrane become lipid laden with age, the lipid composition is characteristically different. This review examines the morphological and biochemical alterations in the senescent Bruch's membrane and its analogy to the vascular wall to evaluate the concurrence of atherosclerosis and AMD.
C1 Kings Coll Hosp London, London SE5 9RS, England.
   Cranfield Univ, Biomed Ctr, Inst Biosci & Technol, Silsoe, Beds, England.
C3 King's College Hospital NHS Foundation Trust; King's College Hospital;
   Cranfield University
RP Sivaprasad, S (通讯作者)，Kings Coll Hosp London, Denmark Hill, London SE5 9RS, England.
EM senswathi@aol.com
RI Sivaprasad, S./D-6876-2015; Chong, Ngaihang V/A-5141-2009; Chong,
   Victor/Q-6565-2018
OI Sivaprasad, S./0000-0001-8952-0659; Chong, Victor/0000-0002-7693-522X
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NR 80
TC 40
Z9 41
U1 0
U2 3
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 OCT
PY 2005
VL 33
IS 5
BP 518
EP 523
DI 10.1111/j.1442-9071.2005.01074.x
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 964TC
UT WOS:000231902400017
PM 16181282
DA 2022-11-30
ER

PT J
AU Smith, RT
   Chan, JK
   Nagasaki, T
   Sparrow, JR
   Barbazetto, I
AF Smith, RT
   Chan, JK
   Nagasaki, T
   Sparrow, JR
   Barbazetto, I
TI A method of drusen measurement based on reconstruction of fundus
   background reflectance
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID AGE-RELATED MACULOPATHY; BILATERAL MACULAR DRUSEN; LASER
   PHOTOCOAGULATION; IMAGE-ANALYSIS; SOFT DRUSEN; GRADING SYSTEM;
   CLINICAL-TRIAL; DEGENERATION; PIGMENT; PHOTOGRAPHS
AB Background: The hallmarks of age related macular degeneration (AMD) are the subretinal deposits known as drusen. Current manual methods of drusen segmentation and quantification are laborious and subjective. The authors introduced a digital method and tested it for accuracy and reliability.
   Methods: Fourteen eyes with drusen were selected. The authors digitally reconstructed the macular background using normal background areas ("dots'') fitted to quadratic polynomials in two zones. The model was used to level the reflectance for the purpose of segmenting drusen by a global threshold. Measurements of drusen areas were compared with those of a semi-automated background levelling technique and manual drawings from stereo pairs.
   Results: Intraobserver reproducibility had standard deviations from 0.1% to 4.1%. Interobserver reproducibility yielded 95% limits of agreement of -2.7% to 6.3%. The dots method compared with manual drawings and with the semi-automated method had 95% limits of agreement of -8.3% to 2.8% and -7.1% to 4.8%, respectively.
   Conclusions: The dots method was reproducible and accurate with respect to validated methods. It provided less total operating time and greater precision than that of standard fundus photo grading. With implementation of commercial software, this technique for macular image analysis has potential for use in clinical research.
C1 Columbia Univ Coll Phys & Surg, Harkness Eye Inst, Dept Ophthalmol, New York, NY 10032 USA.
C3 Columbia University
RP Smith, RT (通讯作者)，Columbia Univ Coll Phys & Surg, Harkness Eye Inst, Dept Ophthalmol, 630 W 168th St, New York, NY 10032 USA.
EM rts1@columbia.edu
OI smith, theodore/0000-0002-1693-943X
FU NATIONAL EYE INSTITUTE [R01EY012951, R37EY000431, R01EY000431] Funding
   Source: NIH RePORTER; NEI NIH HHS [EY12951, EY00431] Funding Source:
   Medline
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NR 30
TC 32
Z9 32
U1 0
U2 0
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD JAN
PY 2005
VL 89
IS 1
BP 87
EP 91
DI 10.1136/bjo.2004.042937
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 889CB
UT WOS:000226420000021
PM 15615753
OA Green Published, Bronze, Green Submitted
DA 2022-11-30
ER

PT J
AU Sloan, FA
   Brown, DS
   Carlisle, ES
   Ostermann, J
   Lee, PP
AF Sloan, FA
   Brown, DS
   Carlisle, ES
   Ostermann, J
   Lee, PP
TI Estimates of incidence rates with longitudinal claims data
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID OPEN-ANGLE GLAUCOMA; AGE-RELATED MACULOPATHY; DIABETIC-RETINOPATHY;
   5-YEAR INCIDENCE; EPIDEMIOLOGICAL COHORT; HMO ENROLLEES; BARBADOS EYE;
   PROGRESSION; PREVALENCE; DIAGNOSIS
AB Objective: To estimate incidence rates of the 3 major chronic eye diseases-diabetic retinopathy (DR), glaucoma, and age-related macular degeneration (ARMD)-by using longitudinal claims data from Medicare.
   Methods: Longitudinal cases were ascertained by using a national probability sample of Medicare beneficiaries aged 65 years and older in 1991 who initially had none of the eye diseases documented. After adjusting for death and enrollment in a health maintenance organization, claims filed by optometrists or ophthalmologists with an International Classification of Diseases, Ninth Revision, Clinical Modification code for all forms of DR, glaucoma, and ARMD were used to indicate diagnosis.
   Results: Annual incidence rates for the 3 conditions after the first year of observation ranged from 14.3% to 17.7% (higher earlier) across an 8-year longitudinal follow-up. Incidence rates among those with diabetes mellitus for any form of DR varied between 3.8% and 6.5%, while those for glaucoma varied between 4.6% and 7.8% and those for ARMD varied between 7.5% and 9.3%.
   Conclusions: Longitudinal claims data after the first year provide relatively stable estimates of incidence rates on an annual basis. These estimates are comparable with those of the few population-based studies available.
C1 Duke Univ, Ctr Hlth Policy Law & Management, Durham, NC 27708 USA.
   Duke Univ, Dept Econ, Durham, NC 27708 USA.
   Duke Univ, Dept Ophthalmol, Sch Med, Durham, NC 27708 USA.
C3 Duke University; Duke University; Duke University
RP Sloan, FA (通讯作者)，Duke Univ, Ctr Hlth Policy Law & Management, Box 90253, Durham, NC 27708 USA.
RI Brown, Derek S/J-3035-2013; Ostermann, Jan/GQB-4743-2022
OI Brown, Derek S/0000-0001-9908-9882; Lee, Paul/0000-0002-3338-136X;
   Ostermann, Jan/0000-0002-8236-9500
FU NIA NIH HHS [R01-AG-14743] Funding Source: Medline
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NR 28
TC 29
Z9 29
U1 0
U2 10
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 OCT
PY 2003
VL 121
IS 10
BP 1462
EP 1468
DI 10.1001/archopht.121.10.1462
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 732FL
UT WOS:000185930100015
PM 14557184
OA Bronze
DA 2022-11-30
ER

PT J
AU Mirra, S
   Sanchez-Bellver, L
   Casale, C
   Pescatore, A
   Marfany, G
AF Mirra, Serena
   Sanchez-Bellver, Laura
   Casale, Carmela
   Pescatore, Alessandra
   Marfany, Gemma
TI Ubiquitin Specific Protease USP48 Destabilizes NF-kappa B/p65 in Retinal
   Pigment Epithelium Cells
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE USP48; retina; NF-kappa B pathway
ID NF-KAPPA-B; TNF-ALPHA; TRANSCRIPTION; ACTIVATION; TERMINATION;
   EXPRESSION; PRECURSOR; NUCLEUS; PATHWAY; GENES
AB Activation of NF-kappa B transcription factor is strictly regulated to accurately direct cellular processes including inflammation, immunity, and cell survival. In the retina, the modulation of the NF-kappa B pathway is essential to prevent excessive inflammatory responses, which plays a pivotal role in many retinal neurodegenerative diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), and inherited retinal dystrophies (IRDs). A critical cytokine mediating inflammatory responses in retinal cells is tumor necrosis factor-alpha (TNF alpha), leading to the activation of several transductional pathways, including NF-kappa B. However, the multiple factors orchestrating the appropriate regulation of NF-kappa B in retinal cells still remain unclear. The present study explores how the ubiquitin-specific protease 48 (USP48) downregulation impacts the stability and transcriptional activity of NF-kappa B/p65 in retinal pigment epithelium (RPE), at both basal conditions and following TNF alpha stimulation. We described that USP48 downregulation stabilizes p65. Notably, the accumulation of p65 is mainly detectable in the nuclear compartment and it is accompanied by an increased NF-kappa B transcriptional activity. These results delineate a novel role of USP48 in negatively regulating NF-kappa B in retinal cells, providing new opportunities for therapeutic intervention in retinal pathologies.
C1 [Mirra, Serena; Sanchez-Bellver, Laura; Marfany, Gemma] Univ Barcelona, Dept Genet Microbiol & Stat, Avda Diagonal 643, Barcelona 08028, Spain.
   [Mirra, Serena; Sanchez-Bellver, Laura; Marfany, Gemma] Inst Salud Carlos III, CIBERER, Madrid 28029, Spain.
   [Mirra, Serena; Marfany, Gemma] Univ Barcelona, Inst Biomed Inst Recerca St Joan de Deu IBUB IRSJ, Barcelona 08028, Spain.
   [Casale, Carmela; Pescatore, Alessandra] Adriano Buzzati Traverso CNR, Inst Genet & Biophys, Via Pietro Castellino 111, I-80131 Naples, Italy.
C3 University of Barcelona; CIBER - Centro de Investigacion Biomedica en
   Red; CIBERER; Instituto de Salud Carlos III; University of Barcelona;
   Consiglio Nazionale delle Ricerche (CNR); Istituto di Genetica e
   Biofisica "Adriano Buzzati-Traverso" (IGB-CNR)
RP Mirra, S; Marfany, G (通讯作者)，Univ Barcelona, Dept Genet Microbiol & Stat, Avda Diagonal 643, Barcelona 08028, Spain.; Mirra, S; Marfany, G (通讯作者)，Inst Salud Carlos III, CIBERER, Madrid 28029, Spain.; Mirra, S; Marfany, G (通讯作者)，Univ Barcelona, Inst Biomed Inst Recerca St Joan de Deu IBUB IRSJ, Barcelona 08028, Spain.
EM serena.mirra@ub.edu; gmarfany@ub.edu
FU FI-DGR grant (Generalitat de Catalunya); SHORT MOBILITY GRANT
   (CIBERER/ISCIII); Ministerio de Ciencia e Innovacion/FEDER
   [PID2019-108578RB-I00]
FX S.M. has a postdoctoral contract with CIBERER/ISCIII, L.S.-B. is
   recipient of the FI-DGR grant (Generalitat de Catalunya). This research
   was supported by grants SHORT MOBILITY GRANT (CIBERER/ISCIII) to S.M.
   and PID2019-108578RB-I00 (Ministerio de Ciencia e Innovacion/FEDER) to
   G.M. and S.M.
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NR 53
TC 1
Z9 1
U1 1
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 SEP
PY 2022
VL 23
IS 17
AR 9682
DI 10.3390/ijms23179682
PG 15
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA 4J2WF
UT WOS:000851128200001
PM 36077078
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Zhang, XZ
   Li, ML
   Li, BH
   Liao, NY
   Wei, ZY
   Gao, JM
   Sun, YX
   Chen, JH
   Rao, JH
   Wen, F
AF Zhang, Xiongze
   Li, Miaoling
   Li, Bihai
   Liao, Nanying
   Wei, Zhiyuan
   Gao, Jiangmei
   Sun, Yunxiao
   Chen, Jianhuan
   Rao, Junhua
   Wen, Feng
TI Ageing fundus degenerations of Macaca fascicularis on multi-modal
   imaging and histopathology: Similarities and differences compared to
   human
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; ONSET MACULAR DEGENERATION; INDOCYANINE
   GREEN; RHESUS-MONKEY; SOFT DRUSEN; AGE; MACULOPATHY; PREVALENCE;
   EVOLUTION; DISEASE
AB To characterize the ageing fundus degenerations in Macaca fascicularis, we used multimodal imaging including color fundus photograph, spectral domain optical coherence tomography, fundus autofluorescence, fundus fluorescence angiography, and indocyanine green angiography (ICGA) to survey and track fundus changes of 84 Macaca fascicularis, ranging from 5 to 24 years old over 2 years, and followed by hematoxylin-eosin (HE) and immunofluorescence (IF) staining. The Macaca fascicularis in our cohort showed ageing characteristics different from human, including the more common yellow dot maculopathy, the unique appearance of patchy hyperautoflurescence, and the absence of subretinal drusenoid deposit, basal laminar deposit, geographic atrophy or choroidal neovascularization. Same with human, hard drusen, soft drusen, atherosclerosis, tessellated retina, staining of vessels in peripheral choroid on late-phase ICGA, and peripheral hard drusen were detected. HE and IF staining suggested the patchy hyperautoflurescence to be drusenoid deposits. BMI were significantly higher in the Macaca fascicularis with yellow dot maculopathy and hard drusen, compared to the ones without (p < 0.05). Our study reveals fundus degenerations that develop with ageing in the nonhuman primate of Macaca fascicularis. Their differences and similarities compared to human worth notice by future translational research in degenerative fundus diseases, especially age-related macular degeneration.
C1 [Zhang, Xiongze; Li, Miaoling; Liao, Nanying; Wen, Feng] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangdong Prov Key Lab Ophthalmol & Visual Sci, Guangzhou, Peoples R China.
   [Li, Bihai; Gao, Jiangmei; Sun, Yunxiao; Chen, Jianhuan; Rao, Junhua] Guangdong Acad Sci, Inst Zool, Guangdong Key Lab Anim Conservat & Resource Utiliz, Guangdong Publ Lab Wild Anim Conservat & Utilizat, Guangzhou, Peoples R China.
   [Wei, Zhiyuan; Chen, Jianhuan] Jiangnan Univ, Wuxi Sch Med, Lab Genom & Precis Med, Wuxi, Peoples R China.
   [Wen, Feng] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangdong Prov Key Lab Ophthalmol & Visual Sci, 54 South Xianlie Rd, Guangzhou 510060, Peoples R China.
   [Rao, Junhua] Guangdong Acad Sci, Inst Zool, 105 Xinggang Rd West, Guangzhou 510260, Peoples R China.
   [Chen, Jianhuan] Jiangnan Univ, Wuxi Sch Med, 1800 lihu Ave, Wuxi 214122, Peoples R China.
C3 Sun Yat Sen University; Guangdong Academy of Sciences; Institute of
   Zoology, Guangdong Academy of Sciences; Jiangnan University; Sun Yat Sen
   University; Guangdong Academy of Sciences; Institute of Zoology,
   Guangdong Academy of Sciences; Jiangnan University
RP Chen, JH; Rao, JH (通讯作者)，Guangdong Acad Sci, Inst Zool, Guangdong Key Lab Anim Conservat & Resource Utiliz, Guangdong Publ Lab Wild Anim Conservat & Utilizat, Guangzhou, Peoples R China.; Wen, F (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangdong Prov Key Lab Ophthalmol & Visual Sci, 54 South Xianlie Rd, Guangzhou 510060, Peoples R China.; Rao, JH (通讯作者)，Guangdong Acad Sci, Inst Zool, 105 Xinggang Rd West, Guangzhou 510260, Peoples R China.; Chen, JH (通讯作者)，Jiangnan Univ, Wuxi Sch Med, 1800 lihu Ave, Wuxi 214122, Peoples R China.
EM cjh_bio@hotmail.com; junhuar919@163.com; wenfeng208@foxmail.com
FU National Natural Science Foundation of China [81870674, 82070970,
   31671311]; Science & Technology~Planing Project of Guangdong
   [2017A070702014, 2014B070706020]; Guangdong Provincial Natural Science
   Foundation [2019A1515012062]
FX This work was supported by the National Natural Science Foundation of
   China (81870674, 82070970, 31671311), Science & Technology Planing
   Project of Guangdong (2017A070702014, 2014B070706020) and Guangdong
   Provincial Natural Science Foundation (2019A1515012062).
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NR 42
TC 0
Z9 0
U1 2
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD JUL
PY 2022
VL 220
AR 109126
DI 10.1016/j.exer.2022.109126
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 2N4YI
UT WOS:000818386000004
PM 35618041
DA 2022-11-30
ER

PT J
AU Garland, DL
   Pierce, EA
   Fernandez-Godino, R
AF Garland, Donita L.
   Pierce, Eric A.
   Fernandez-Godino, Rosario
TI Complement C5 is not critical for the formation of sub-RPE deposits in
   Efemp1 mutant mice
SO SCIENTIFIC REPORTS
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; ALTERNATIVE PATHWAY;
   GEOGRAPHIC ATROPHY; TISSUE INHIBITOR; DRUSEN FORMATION; MATRIX;
   MUTATION; MODEL; GENETICS
AB The complement system plays a role in the formation of sub-retinal pigment epithelial (RPE) deposits in early stages of age-related macular degeneration (AMD). But the specific mechanisms that connect complement activation and deposit formation in AMD patients are unknown, which limits the development of efficient therapies to reduce or stop disease progression. We have previously demonstrated that C3 blockage prevents the formation of sub-RPE deposits in a mouse model of EFEMP1-associated macular degeneration. In this study, we have used double mutant Efemp1(R345W/R345W):C5(-/-) mice to investigate the role of C5 in the formation of sub-RPE deposits in vivo and in vitro. The data revealed that the genetic ablation of C5 does not eliminate the formation of sub-RPE deposits. Contrarily, the absence of C5 in RPE cultures promotes complement dysregulation that results in increased activation of C3, which likely contributes to deposit formation even in the absence of EFEMP1-R345W mutant protein. The results also suggest that genetic ablation of C5 alters the extracellular matrix turnover through an effect on matrix metalloproteinases in RPE cell cultures. These results confirm that C3 rather than C5 could be an effective therapeutic target to treat early AMD.
C1 [Garland, Donita L.; Pierce, Eric A.; Fernandez-Godino, Rosario] Harvard Med Sch, Ocular Genom Inst Massachusetts Eye & Ear, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School
RP Fernandez-Godino, R (通讯作者)，Harvard Med Sch, Ocular Genom Inst Massachusetts Eye & Ear, Boston, MA 02115 USA.
EM godino@meei.harvard.edu
FU Ocular Genomics Institute; National Eye Institute Core grant
   [P30EY003790]
FX This work was supported by the Ocular Genomics Institute. The TEM work
   was supported in part by a National Eye Institute Core grant
   (P30EY003790). The authors would like to thank Schepens Eye Research
   Institute morphology core facility, especially Philip Seifert for
   performing the TEM, and Ann Tisdale for helpful technical assistance
   with SM.
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NR 59
TC 3
Z9 3
U1 0
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 MAY 17
PY 2021
VL 11
IS 1
AR 10416
DI 10.1038/s41598-021-89978-8
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA SN6YB
UT WOS:000658432900001
PM 34001980
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Taher, F
   Kandil, H
   Mahmoud, H
   Mahmoud, A
   Shalaby, A
   Ghazal, M
   Alhalabi, MT
   Sandhu, HS
   El-Baz, A
AF Taher, Fatma
   Kandil, Heba
   Mahmoud, Hatem
   Mahmoud, Ali
   Shalaby, Ahmed
   Ghazal, Mohammed
   Alhalabi, Marah Talal
   Sandhu, Harpal Singh
   El-Baz, Ayman
TI A Comprehensive Review of Retinal Vascular and Optical Nerve Diseases
   Based on Optical Coherence Tomography Angiography
SO APPLIED SCIENCES-BASEL
LA English
DT Article
DE optical nerve diseases; OCTA; retinal; vascular diseases
ID FOVEAL AVASCULAR ZONE; DIABETIC MACULAR EDEMA; GROWTH-FACTOR THERAPY;
   OPEN-ANGLE GLAUCOMA; CHOROIDAL NEOVASCULARIZATION; VEIN OCCLUSION;
   VESSEL DENSITY; VISUAL-ACUITY; FLUORESCEIN ANGIOGRAPHY; CAPILLARY
   NONPERFUSION
AB The optical coherence tomography angiography (OCTA) is a noninvasive imaging technology which aims at imaging blood vessels in retina by studying decorrelation signals between multiple sequential OCT B-scans captured in the same cross section. Obtaining various vascular plexuses including deep and superficial choriocapillaris, is possible, which helps in understanding the ischemic processes that affect different retina layers. OCTA is a safe imaging modality that does not use dye. OCTA is also fast as it can capture high-resolution images in just seconds. Additionally, it is used in the assessment of structure and blood flow. OCTA provides anatomic details in addition to the vascular flow data. These details are important in understanding the tissue perfusion, specifically, in the absence of apparent morphological change. Using these anatomical details along with perfusion data, OCTA could be used in predicting several ophthalmic diseases. In this paper, we review the OCTA techniques and their ability to detect and diagnose several retinal vascular and optical nerve diseases, such as diabetic retinopathy (DR), anterior ischemic optic neuropathy (AION), age-related macular degeneration (AMD), glaucoma, retinal artery occlusion and retinal vein occlusion. Then, we discuss the main features and disadvantages of using OCTA as a retinal imaging method.
C1 [Taher, Fatma] Zayed Univ, Coll Technol Innovat, Dubai 19282, U Arab Emirates.
   [Kandil, Heba; Mahmoud, Ali; Shalaby, Ahmed; El-Baz, Ayman] Univ Louisville, Bioengn Dept, Louisville, KY 40292 USA.
   [Mahmoud, Hatem] Al Azhar Univ, Fac Med, Ophthalmol Dept, Cairo 11651, Egypt.
   [Ghazal, Mohammed; Alhalabi, Marah Talal] Abu Dhabi Univ, Elect & Comp Engn Dept, Abu Dhabi 59911, U Arab Emirates.
   [Sandhu, Harpal Singh] Univ Louisville, Sch Med, Ophthalmol Dept, Louisville, KY 40292 USA.
C3 Zayed University; University of Louisville; Egyptian Knowledge Bank
   (EKB); Al Azhar University; Abu Dhabi University; University of
   Louisville
RP El-Baz, A (通讯作者)，Univ Louisville, Bioengn Dept, Louisville, KY 40292 USA.
EM fatma.taher@zu.ac.ae; hekand01@louisville.edu; hatem.samy@hotmail.com;
   ahmahm01@louisville.edu; ahmed.shalaby@louisville.edu;
   mohammed.ghazal@adu.ac.ae; marah.alhalabi@adu.ac.ae;
   harpal.sandhu@gmail.com; aselba01@louisville.edu
RI Taher, Fatma/AAA-2912-2021; Kandil, Heba/N-6641-2019; El-Baz,
   Ayman/AAC-6689-2019
OI Taher, Fatma/0000-0001-8358-9081; El-Baz, Ayman/0000-0001-7264-1323;
   Ghazal, Mohammed/0000-0002-9045-6698; kandil, heba/0000-0002-5531-5574;
   Alhalabi, Marah/0000-0001-8190-5263; Shalaby, Ahmed/0000-0001-6291-7998
FU Abu Dhabi Award for Research Excellence (AARE) 2019
FX This work is supported, in part, by the Abu Dhabi Award for Research
   Excellence (AARE) 2019.
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NR 186
TC 1
Z9 1
U1 1
U2 3
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2076-3417
J9 APPL SCI-BASEL
JI Appl. Sci.-Basel
PD MAY
PY 2021
VL 11
IS 9
AR 4158
DI 10.3390/app11094158
PG 28
WC Chemistry, Multidisciplinary; Engineering, Multidisciplinary; Materials
   Science, Multidisciplinary; Physics, Applied
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry; Engineering; Materials Science; Physics
GA SB3ZN
UT WOS:000649936800001
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Desideri, LF
   Traverso, CE
   Nicolo, M
AF Ferro Desideri, Lorenzo
   Traverso, Carlo Enrico
   Nicolo, Massimo
TI Brolucizumab: a novel anti-VEGF humanized single-chain antibody fragment
   for treating w-AMD
SO EXPERT OPINION ON BIOLOGICAL THERAPY
LA English
DT Article
DE Brolucizumab; macular degeneration; anti-VEGF; novel anti-VEGF agent;
   HAWK; HARRIER
ID MACULAR DEGENERATION; PATIENT PREFERENCES; MANAGEMENT; OUTCOMES; DOMAIN;
   AGENTS; FV
AB Introduction
   Wet age-related macular degeneration (w-AMD) represents the leading cause of visual impairment in the elderly in the developed countries. Intravitreal antivascular endothelial growth factor (VEGF) drugs are currently considered as the first-line treatment option for treating w-AMD; however, the frequent injection intervals have lit the way to investigate novel anti-VEGF agents allowing a more extended treatment regimen. Brolucizumab is a single-chain antibody fragment targeting all the isoforms of VEGF-A. Phase III HAWK and HARRIER trials have shown a longer durability and superior anatomical outcomes as compared with the standard of care by adopting a quarterly regimen for treating w-AMD. Brolucizumab has been approved in Europe, USA, and Japan for the management of w-AMD.
   Areas covered
   This article presents an overview of w-AMD and investigates the progress of brolucizumab through clinical trials. It offers insights into where brolucizumab may be placed in the current market of anti-VEGF agents and its potential advantages over the previous molecules adopted for treating w-AMD.
   Expert Opinion
   The possibility of administering brolucizumab with more dilated treatment intervals represents an important advantage to decrease the treatment burden and improve patient compliance. Brolucizumab represents a possible drug switching option in non-responding patients to other anti-VEGF drugs.
C1 [Ferro Desideri, Lorenzo; Traverso, Carlo Enrico; Nicolo, Massimo] Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, Genoa, Italy.
   [Traverso, Carlo Enrico; Nicolo, Massimo] Osped Policlin San Martino IRCCS, Genoa, Italy.
   [Nicolo, Massimo] Fdn Macula Onlus, Genoa, Italy.
C3 University of Genoa
RP Nicolo, M (通讯作者)，DiNOGMI Osped Policlin San Martino IRCCS, Clin Oculist, Viale Benedetto XV, I-16132 Genoa, Italy.
EM massimo.nicolo@gmail.com
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NR 73
TC 11
Z9 11
U1 0
U2 0
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1471-2598
EI 1744-7682
J9 EXPERT OPIN BIOL TH
JI Expert Opin. Biol. Ther.
PD MAY 4
PY 2021
VL 21
IS 5
BP 553
EP 561
DI 10.1080/14712598.2021.1915278
EA APR 2021
PG 9
WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Research & Experimental Medicine
GA RV4XT
UT WOS:000643836700001
PM 33899632
DA 2022-11-30
ER

PT J
AU Song, I
   Kim, J
   Baek, K
   Choi, Y
   Shin, B
   Jin, E
AF Song, Inhwa
   Kim, Jongrae
   Baek, Kwangryul
   Choi, Young
   Shin, ByongCheol
   Jin, EonSeon
TI The generation of metabolic changes for the production of high-purity
   zeaxanthin mediated by CRISPR-Cas9 in Chlamydomonas reinhardtii
SO MICROBIAL CELL FACTORIES
LA English
DT Article
DE Zeaxanthin production; Retinal pigment; CRISPR-Cas9; Lycopene epsilon
   cyclase; Chlamydomonas reinhardtii
ID MACULAR PIGMENT; PHOTOSYSTEM-I; LUTEIN; CAROTENOIDS; BIOSYNTHESIS;
   ACCUMULATION; VIOLAXANTHIN; ENHANCEMENT; EXTRACTION; SYNTHASE
AB Background Zeaxanthin, a major xanthophyll pigment, has a significant role as a retinal pigment and antioxidant. Because zeaxanthin helps to prevent age-related macular degeneration, its commercial use in personalized nutritional and pharmaceutical applications has expanded. To meet the quantitative requirements for personalized treatment and pharmaceutical applications, it is necessary to produce highly purified zeaxanthin. Results In this study, to meet the quantitative requirements for industrial applications, we generated a double knockout mutant which is gene-edited by the CRISPR-Cas9 ribonucleoprotein-mediated knock-in system. The lycopene epsilon cyclase (LCYE) was edited to the elimination of alpha-branch of xanthophyll biosynthesis in a knockout mutant of the zeaxanthin epoxidase gene (ZEP). The double knockout mutant (dzl) had a 60% higher zeaxanthin yield (5.24 mg L- 1) and content (7.28 mg g(- 1)) than that of the parental line after 3 days of cultivation. Furthermore, medium optimization improved the 3-day yield of zeaxanthin from the dzl mutant to 6.84 mg L- 1. Conclusions A Chlamydomonas strain with the elimination of lutein production by gene editing using CRISPR-Cas9 has been successfully developed. This research presents a solution to overcome the difficulties of the downstream-process for the production of high-purity zeaxanthin.
C1 [Song, Inhwa; Kim, Jongrae; Baek, Kwangryul; Jin, EonSeon] Hanyang Univ, Res Inst Nat Sci, Dept Life Sci, 222 Wangsimni Ro, Seoul 04763, South Korea.
   [Choi, Young; Shin, ByongCheol] Arca Eir, Daedeok Biz Ctr, C-323,17 Techno4-ro, Daejeon 34013, South Korea.
C3 Hanyang University
RP Jin, E (通讯作者)，Hanyang Univ, Res Inst Nat Sci, Dept Life Sci, 222 Wangsimni Ro, Seoul 04763, South Korea.
EM esjin@hanyang.ac.kr
OI Jin, EonSeon/0000-0001-5691-0124
FU Ministry of Oceans and Fisheries, Korea [20190066]; Korea government
   (MSIT) [KCRC-2014M1A8A1 049273, NRF-2020R1A2C2011998]
FX This research was funded by the Ministry of Oceans and Fisheries, Korea
   (20190066), and also funded by the Korea government (MSIT)
   (KCRC-2014M1A8A1 049273, NRF-2020R1A2C2011998).
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NR 33
TC 10
Z9 10
U1 5
U2 25
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 1475-2859
J9 MICROB CELL FACT
JI Microb. Cell. Fact.
PD DEC 30
PY 2020
VL 19
IS 1
AR 220
DI 10.1186/s12934-020-01480-4
PG 9
WC Biotechnology & Applied Microbiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology
GA PB4MQ
UT WOS:000596297200002
PM 33256757
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Bussing, D
   Shah, DK
AF Bussing, David
   K. Shah, Dhaval
TI Development of a physiologically-based pharmacokinetic model for ocular
   disposition of monoclonal antibodies in rabbits
SO JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS
LA English
DT Article
DE Eye; Ocular pharmacokinetics; Antibody; Rabbit; Physiologically-based
   pharmacokinetic model
ID PBPK MODEL; INTRAVITREAL PHARMACOKINETICS; TISSUE DISTRIBUTION; VASCULAR
   DENSITY; DRUG-DELIVERY; VENOM; FLOW; COMPARTMENTS; BEVACIZUMAB;
   PARAMETERS
AB Development of protein therapeutics for ocular disorders, particularly age-related macular degeneration (AMD), is a highly competitive and expanding therapeutic area. However, the application of a predictive and translatable ocular PK model to better understand ocular disposition of protein therapeutics, such as a physiologically-based pharmacokinetic (PBPK) model, is missing from the literature. Here, we present an expansion of an antibody platform PBPK model towards rabbit and incorporate a novel anatomical and physiologically relevant ocular component. Parameters describing all tissues, flows, and binding events were obtained from existing literature and fixed a priori. First, translation of the platform PBPK model to rabbit was confirmed by evaluating the model's ability to predict plasma PK of a systemically administered exogenous antibody. Then, the PBPK model with the new ocular component was validated by estimation of serum and ocular (i.e. aqueous humor, retina, and vitreous humor) PK of two intravitreally administered monoclonal antibodies. We show that the proposed PBPK model is capable of accurately (i.e. within twofold) predicting ocular exposure of antibody-based drugs. The proposed PBPK model can be used for preclinical-to-clinical translation of antibodies developed for ocular disorders, and assessment of ocular toxicity for systemically administered antibody-based therapeutics.
C1 [Bussing, David; K. Shah, Dhaval] SUNY Buffalo, Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, 455 Pharm Bldg, Buffalo, NY 14214 USA.
C3 State University of New York (SUNY) System; State University of New York
   (SUNY) Buffalo
RP Shah, DK (通讯作者)，SUNY Buffalo, Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, 455 Pharm Bldg, Buffalo, NY 14214 USA.
EM dshah4@buffalo.edu
OI Shah, Dhaval/0000-0002-0723-6206
FU NIH [GM114179, AI138195, R01CA246785]
FX D.K.S is supported by NIH grants GM114179, AI138195, and R01CA246785.
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NR 58
TC 5
Z9 5
U1 0
U2 6
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1567-567X
EI 1573-8744
J9 J PHARMACOKINET PHAR
JI J. Pharmacokinet. Pharmacodyn.
PD DEC
PY 2020
VL 47
IS 6
BP 597
EP 612
DI 10.1007/s10928-020-09713-0
EA SEP 2020
PG 16
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA OP9BC
UT WOS:000565502400001
PM 32876799
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Song, JY
   Fan, B
   Che, L
   Pan, YR
   Zhang, SM
   Wang, Y
   Bunik, V
   Li, GY
AF Song, Jing-Yao
   Fan, Bin
   Che, Lin
   Pan, Yi-Ran
   Zhang, Si-Ming
   Wang, Ying
   Bunik, Victoria
   Li, Guang-Yu
TI Suppressing endoplasmic reticulum stress-related autophagy attenuates
   retinal light injury
SO AGING-US
LA English
DT Article
DE oxidative stress; ER stress; autophagy; AMD; PERK
ID UNFOLDED PROTEIN RESPONSE; OXIDATIVE STRESS; ER STRESS; PHOTOCHEMICAL
   DAMAGE; INDUCED EXPRESSION; SUNLIGHT EXPOSURE; RISK-FACTOR; DNA-DAMAGE;
   DEGENERATION; PATHWAY
AB Excessive light exposure is a principal environmental factor, which can cause damage to photoreceptors and retinal pigment epithelium (RPE) cells and may accelerate the progression of age-related macular degeneration (AMD). In this study, oxidative stress, endoplasmic reticulum (ER) stress and autophagy caused by light exposure were evaluated in vitro and in vivo. Light exposure caused severe photo-oxidative stress and ER stress in photoreceptors (661W cells) and RPE cells (ARPE-19 cells). Suppressing either oxidative stress or ER stress was protective against light damage in 661W and ARPE-19 cells and N-acetyl-L-cysteine treatment markedly inhibited the activation of ER stress caused by light exposure. Moreover, suppressing autophagy with 3-methyladenine significantly attenuated light-induced cell death. Additionally, inhibiting ER stress either by knocking down PERK signals or with GSK2606414 treatment remarkably suppressed prolonged autophagy and protected the cells against light injury. In vivo experiments verified neuroprotection via inhibiting ER stress-related autophagy in light-damaged retinas of mice. In conclusion, the above results suggest that light-induced photo-oxidative stress may trigger subsequent activation of ER stress and prolonged autophagy in photoreceptors and RPE cells. Suppressing ER stress may abrogate over-activated autophagy and protect the retina against light injury.
C1 [Song, Jing-Yao; Fan, Bin; Che, Lin; Pan, Yi-Ran; Zhang, Si-Ming; Li, Guang-Yu] Second Hosp Jilin Univ, Dept Ophthalmol, Changchun, Peoples R China.
   [Wang, Ying] Second Hosp Jilin Univ, Dept Hemooncolog, Changchun, Peoples R China.
   [Bunik, Victoria] Lomonosov Moscow State Univ, AN Belozersky Inst Physicochem Biol, Moscow, Russia.
C3 Jilin University; Jilin University; Lomonosov Moscow State University
RP Li, GY (通讯作者)，Second Hosp Jilin Univ, Dept Ophthalmol, Changchun, Peoples R China.
EM l_gy@jlu.edu.cn
FU National Natural Science Foundation of China [81570864]; Natural Science
   Foundation of Jilin Province [20200801043GH, 20200201379JC, 201902
   01083JC]; Science and Technology Project of Jilin Provincial Education
   Department [JJKH20190046KJ, JJKH20190049KJ]
FX This work was supported by grants from the National Natural Science
   Foundation of China (No. 81570864), the Natural Science Foundation of
   Jilin Province (No. 20200801043GH, No.20200201379JC, No.201902 01083JC)
   and the Science and Technology Project of Jilin Provincial Education
   Department (No. JJKH20190046KJ, No. JJKH20190049KJ). 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 54
TC 8
Z9 10
U1 11
U2 36
PU IMPACT JOURNALS LLC
PI ORCHARD PARK
PA 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD AUG 31
PY 2020
VL 12
IS 16
BP 16579
EP 16596
DI 10.18632/aging.103846
PG 18
WC Cell Biology; Geriatrics & Gerontology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Geriatrics & Gerontology
GA NM2AQ
UT WOS:000567905300008
PM 32858529
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Dvoriashyna, M
   Foss, AJE
   Gaffney, EA
   Jensen, OE
   Repetto, R
AF Dvoriashyna, Mariia
   Foss, Alexander J. E.
   Gaffney, Eamonn A.
   Jensen, Oliver E.
   Repetto, Rodolfo
TI Osmotic and electroosmotic fluid transport across the retinal pigment
   epithelium: A mathematical model
SO JOURNAL OF THEORETICAL BIOLOGY
LA English
DT Article
DE Epithelial transport; Fluid accumulation in the sub-retinal space;
   Electroosmosis; Local osmosis
ID CORNEAL ENDOTHELIUM; ION-TRANSPORT; CL-TRANSPORT; TIGHT JUNCTIONS; WATER
   TRANSPORT; ELCTROOSMOSIS; MECHANISMS; CHANNELS; FLOW; PERMEABILITY
AB The retinal pigment epithelium (RPE) is the outermost cell layer of the retina. It has several important physiological functions, among which is removal of excess fluid from the sub-retinal space by pumping it isotonically towards the choroid. Failure of this pumping leads to fluid accumulation, which is closely associated with several pathological conditions, such as age-related macular degeneration, macular oedema and retinal detachment. In the present work we study mechanisms responsible for fluid transport across the RPE with the aim of understanding how fluid accumulation can be prevented. We focus on two possible mechanisms, osmosis and electroosmosis, and develop a spatially resolved mathematical model that couples fluid and ion transport across the epithelium, accounting for the presence of Na+, K+ and Cl- ions. Our model predicts spatial variability of ion concentrations and the electrical potential along the cleft gap between two adjacent cells, which osmotically drives the flow across the lateral membranes. This flow is directed from the sub-retinal space to the choroid and has a magnitude close to measured values. Electroosmosis is subdominant by three orders of magnitude to osmosis and has an opposite direction, suggesting that local osmosis is the main driving mechanism for water transport across the RPE. (C) 2018 Elsevier Ltd. All rights reserved.
C1 [Dvoriashyna, Mariia; Repetto, Rodolfo] Univ Genoa, Dept Civil Chem & Environm Engn, Via Montallegro 1, I-16145 Genoa, Italy.
   [Foss, Alexander J. E.] Nottingham Univ Hosp NHS Trust, Dept Ophthalmol, Nottingham NG5 1PB, England.
   [Gaffney, Eamonn A.] Univ Oxford, Wolfson Ctr Math Biol, Math Inst, Oxford OX2 6GG, England.
   [Jensen, Oliver E.] Univ Manchester, Sch Math, Manchester M13 9PL, Lancs, England.
C3 University of Genoa; Nottingham University Hospital NHS Trust;
   University of Oxford; University of Manchester
RP Dvoriashyna, M (通讯作者)，Univ Genoa, Dept Civil Chem & Environm Engn, Via Montallegro 1, I-16145 Genoa, Italy.
EM mariia.dvoriashyna@edu.unige.it
RI Jensen, Oliver/B-5880-2008; DVORIASHYNA, MARIIA/ABF-8848-2021; Repetto,
   Rodolfo/AAQ-4616-2020
OI Jensen, Oliver/0000-0003-0172-6578; DVORIASHYNA,
   MARIIA/0000-0002-6057-1919; Gaffney, Eamonn/0000-0002-6888-4362
FU Macular Society; UK Fluids Network; EPSRC [EP/N032861/1]
FX The work has been supported by the Macular Society and the UK Fluids
   Network, funded by EPSRC grant EP/N032861/1.
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NR 60
TC 7
Z9 7
U1 1
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-5193
EI 1095-8541
J9 J THEOR BIOL
JI J. Theor. Biol.
PD NOV 7
PY 2018
VL 456
BP 233
EP 248
DI 10.1016/j.jtbi.2018.08.009
PG 16
WC Biology; Mathematical & Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
   Biology
GA GU5JI
UT WOS:000445321400020
PM 30096403
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Kayat, KV
   Roisman, L
   Zett, C
   Novais, EA
   Farah, ME
AF Kayat, Kim Vieira
   Roisman, Luiz
   Zett, Claudio
   Novais, Eduardo A.
   Farah, Michel Eid
TI Choriocapillaris Hypoperfusion Artifact in OCT Angiography
SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA
LA English
DT Article
ID AMPLITUDE-DECORRELATION ANGIOGRAPHY; COHERENCE TOMOGRAPHIC ANGIOGRAPHY;
   MOTION CORRECTION; IMAGE ARTIFACTS
AB BACKGROUND AND OBJECTIVE: To illustrate how optical coherence tomography (OCT) angiography (OCTA) can be misinterpreted if not evaluated along with structural en face. OCT to analyze the signal intensity.
   PATIENTS AND METHODS: Patients with different macular diseases associated with suspicious flow impairment in the choriocapillaris were recruited to be imaged on the RTVue XR Avanti device (Optovue, Fremont, CA) with the Angio Retina mode. En face OCT angiograms, structural en face OCT, and corresponding OCT B-scans with flow signal overlaid were compared to evaluate the correspondence of signal strength to areas of flow reduction in the choriocapillaris.
   RESULTS: Six eyes from six patients were enrolled. Macular lesions evaluated in this study included acute central serous chorioretinopathy, paracentral acute middle maculopathy, age-related macular degeneration, adult-onset foveomacular vitelliform dystrophy, and branch retinal vein occlusion. In all cases, areas of suspicious flow decrement in the choriocapillaris corresponded to hyporeflective areas in the intensity en face OCT. Thus, a precise confirmation of choriocapillaris flow impairment was not possible.
   CONCLUSION: It is essential to be aware of the importance of analyzing the structural image alongside with the flow image to interpret flow impairment. This is more important in subretinal pigment epithelial structures such as choriocapillaris and choroid.
C1 [Kayat, Kim Vieira; Zett, Claudio; Novais, Eduardo A.; Farah, Michel Eid] Univ Fed Sao Paulo, Paulista Sch Med, Dept Ophthalmol & Visual Sci, Sao Paulo, Brazil.
   [Zett, Claudio] Pontificia Univ Catolica Valparaiso, Valparaiso, Chile.
C3 Universidade Federal de Sao Paulo (UNIFESP); Pontificia Universidad
   Catolica de Valparaiso
RP Kayat, KV (通讯作者)，Univ Fed Sao Paulo, Dept Oftalmol, Secretaria Adm, Rua Botucatu 821, BR-04023062 Sao Paulo, Brazil.
EM kim_kayat@hotmail.com
RI roisman, luiz/AAD-3822-2019; Farah, Michel Eid E/F-3285-2012
OI Farah, Michel Eid E/0000-0001-5951-0193
FU Ophthalmology Department of the Federal University of Sao Paulo
   (UNIFESP) / School of Medicine (EPM); Instituto da Visao - IPEPO, Sao
   Paulo, Brazil
FX This study was supported by the Ophthalmology Department of the Federal
   University of Sao Paulo (UNIFESP) / School of Medicine (EPM) and
   Instituto da Visao - IPEPO, Sao Paulo, Brazil.
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NR 24
TC 6
Z9 6
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 AUG
PY 2018
VL 49
IS 8
BP 603
EP 610
DI 10.3928/23258160-20180803-08
PG 8
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA GQ7OX
UT WOS:000441934200009
PM 30114305
DA 2022-11-30
ER

PT J
AU Green, YA
   Ben-Yaakov, K
   Adir, O
   Pollack, A
   Dvashi, Z
AF Green, Yaron A.
   Ben-Yaakov, Keren
   Adir, Orit
   Pollack, Ayala
   Dvashi, Zeev
TI TAK1 is involved in the autophagy process in retinal pigment epithelial
   cells
SO BIOCHEMISTRY AND CELL BIOLOGY
LA English
DT Article
DE TAK1; autophagy; RPE; LC3A/B-II; AMD
ID MACULAR DEGENERATION; KINASE; INFLAMMATION; INHIBITION; RPE;
   DIFFERENTIATION; ACTIVATION; SENESCENCE; APOPTOSIS; RAPAMYCIN
AB Autophagy is an evolutionarily conserved mechanism for degrading long-lived or malfunctioning proteins and organelles, such as those resulting from oxidative stress. Several publications have demonstrated the importance of the autophagy process in the pathophysiology of dry age-related macular degeneration (AMD). Still, the mechanism underlying this process and its involvement in dry AMD are not fully characterized. Investigating the autophagy process in retinal pigment epithelial (RPE) cells, we identified transforming growth factor beta activated kinase 1 (TAK1) as a key player in the process. We found increased TAK1 phosphorylation in ARPE-19 and D407 cells treated with different inducers of autophagy, such as oxidative stress and rapamycin. Moreover, utilizing TAK1 specific inhibitor prior to oxidative stress or rapamycin treatment, we found significant reduction in LC3A/ B-II expression. These results point at the involvement of TAK1 in the regulation of autophagy in RPE cells. This study suggests that aberrant activity of this kinase impairs autophagy and subsequently leads to alterations in the vitality of RPE cells. Proper activity of TAK1 may be essential for efficient autophagy, and crucial for the ability of RPE cells to respond to stress and dispose of damaged organelles, thus preventing or delaying retinal pathologies.
C1 [Green, Yaron A.; Ben-Yaakov, Keren; Adir, Orit; Pollack, Ayala; Dvashi, Zeev] Hadassah Hebrew Univ Jerusalem, Kaplan Med Ctr, Rehovot, Israel.
C3 Hebrew University of Jerusalem; Kaplan Medical Center
RP Dvashi, Z (通讯作者)，Hadassah Hebrew Univ Jerusalem, Kaplan Med Ctr, Rehovot, Israel.
EM Zeev.medtech@gmail.com
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NR 60
TC 2
Z9 2
U1 0
U2 7
PU CANADIAN SCIENCE PUBLISHING
PI OTTAWA
PA 65 AURIGA DR, SUITE 203, OTTAWA, ON K2E 7W6, CANADA
SN 0829-8211
EI 1208-6002
J9 BIOCHEM CELL BIOL
JI Biochem. Cell Biol.
PD APR
PY 2016
VL 94
IS 2
BP 188
EP 196
DI 10.1139/bcb-2015-0120
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA DL1OZ
UT WOS:000375402900010
PM 26928052
DA 2022-11-30
ER

PT J
AU Lorden, ER
   Levinson, HM
   Leong, KW
AF Lorden, Elizabeth R.
   Levinson, Howard M.
   Leong, Kam W.
TI Integration of drug, protein, and gene delivery systems with
   regenerative medicine
SO DRUG DELIVERY AND TRANSLATIONAL RESEARCH
LA English
DT Review
DE Regeneration; Drug delivery; Gene delivery; Protein delivery; Biomedical
   engineering; Angiogenesis
ID ENDOTHELIAL GROWTH-FACTOR; PLURIPOTENT STEM-CELLS; SCIATIC-NERVE
   REGENERATION; SIRNA-MEDIATED INHIBITION; BLOOD-VESSEL FORMATION;
   NUCLEIC-ACID DELIVERY; THERAPEUTIC ANGIOGENESIS; SUSTAINED-RELEASE;
   IN-VIVO; MONOCLONAL-ANTIBODY
AB Regenerative medicine has the potential to drastically change the field of health care from reactive to preventative and restorative. Exciting advances in stem cell biology and cellular reprogramming have fueled the progress of this field. Biochemical cues in the form of small molecule drugs, growth factors, zinc finger protein transcription factors and nucleases, transcription activator-like effector nucleases, monoclonal antibodies, plasmid DNA, aptamers, or RNA interference agents can play an important role to influence stem cell differentiation and the outcome of tissue regeneration. Many of these biochemical factors are fragile and must act intracellularly at the molecular level. They require an effective delivery system, which can take the form of a scaffold (e.g., hydrogels and electrospun fibers), carrier (viral and nonviral), nano- and microparticle, or genetically modified cell. In this review, we will discuss the history and current technologies of drug, protein, and gene delivery in the context of regenerative medicine. Next, we will present case examples of how delivery technologies are being applied to promote angiogenesis in nonhealing wounds or prevent angiogenesis in age related macular degeneration. Finally, we will conclude with a brief discussion of the regulatory pathway from bench to bedside for the clinical translation of these novel therapeutics.
C1 [Lorden, Elizabeth R.; Leong, Kam W.] Duke Univ, Dept Biomed Engn, 101 Sci Dr, Durham, NC 27708 USA.
   [Levinson, Howard M.] Duke Univ, Med Ctr, Dept Surg, Div Plast & Reconstruct Surg, Durham, NC 27708 USA.
   [Leong, Kam W.] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia.
C3 Duke University; Duke University; King Abdulaziz University
RP Leong, KW (通讯作者)，Duke Univ, Dept Biomed Engn, 101 Sci Dr, Durham, NC 27708 USA.
EM kam.leong@duke.edu
RI Leong, Kam/O-9302-2019
OI Leong, Kam/0000-0002-8133-4955
FU National Science Foundation; NIH [EB015000, UH2TR000505, K08 GM085562];
   NIH (NIH Common Fund for the Microphysiological Systems Initiative);
   NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UH2TR000505,
   UH3TR000505] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ALLERGY
   AND INFECTIOUS DISEASES [R01AI096305] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
   [R21EB015300] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF
   GENERAL MEDICAL SCIENCES [K08GM085562] Funding Source: NIH RePORTER
FX ERL is grateful for her fellowship assistance from the National Science
   Foundation's Graduate Research Fellowships Program. Support by NIH
   (EB015000, UH2TR000505, K08 GM085562, and the NIH Common Fund for the
   Microphysiological Systems Initiative) is also acknowledged. The authors
   would like to thank Jennifer Bond, PhD for her assistance in editing and
   developing the manuscript.
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NR 159
TC 32
Z9 32
U1 0
U2 76
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 APR
PY 2015
VL 5
IS 2
BP 168
EP 186
DI 10.1007/s13346-013-0165-8
PG 19
WC Instruments & Instrumentation; Medicine, Research & Experimental;
   Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Instruments & Instrumentation; Research & Experimental Medicine;
   Pharmacology & Pharmacy
GA CM0MD
UT WOS:000357371200009
PM 25787742
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Mastropasqua, R
   Di Antonio, L
   Di Staso, S
   Agnifili, L
   Di Gregorio, A
   Ciancaglini, M
   Mastropasqua, L
AF Mastropasqua, Rodolfo
   Di Antonio, Luca
   Di Staso, Silvio
   Agnifili, Luca
   Di Gregorio, Angela
   Ciancaglini, Marco
   Mastropasqua, Leonardo
TI Optical Coherence Tomography Angiography in Retinal Vascular Diseases
   and Choroidal Neovascularization
SO JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID FLUORESCEIN ANGIOGRAPHY; PERFUSION; LAYERS
AB Purpose. To assess the ability of optical coherence tomography-angiography (OCT-A) to show and analyze retinal vascular patterns and the choroidal neovascularization (CNV) in retinal vascular diseases. Methods. Seven eyes of seven consecutive patients with retinal vascular diseases were examined. Two healthy subjects served as controls. All eyes were scanned with the SD-OCT XR Avanti (Optovue Inc, Fremont CA, USA). Split spectrum amplitude decorrelation angiography algorithm was used to identify the blood flow within the tissue. Fluorescein angiography (FA) and indocyanine green angiography (ICGA) with Spectralis HRA + OCT (Heidelberg Engineering GmbH) were performed. Results. In healthy subjects OCT-A visualized major macular vessels and detailed capillary networks around the foveal avascular zone. Patients were affected with myopic CNV (2 eyes), age-related macular degeneration related (2), branch retinal vein occlusion (BRVO) (2), and branch retinal artery occlusion (BRAO) (1). OCTA images provided distinct vascular patterns, distinguishing perfused and nonperfused areas in BRVO and BRAO and recognizing the presence, location, and size of CNV. Conclusions. OCT-A provides detailed images of retinal vascular plexuses and quantitative data of pathologic structures. Further studies are warranted to define the role of OCT-A in the assessment of retinovascular diseases, with respect to conventional FA and ICG-A.
C1 [Mastropasqua, Rodolfo] Univ Verona, Dept Neurol Neuropsychol Morphol & Movement Sci, Ophthalmol Unit, I-37100 Verona, Italy.
   [Di Antonio, Luca; Agnifili, Luca; Mastropasqua, Leonardo] Univ G dAnnunzio, Dept Med & Aging Sci, Ophthalmol Clin, I-66100 Chieti, Italy.
   [Di Staso, Silvio; Di Gregorio, Angela; Ciancaglini, Marco] Univ Aquila, Dept Life Hlth & Environm Sci, Eye Clin, I-67100 Laquila, Italy.
C3 University of Verona; G d'Annunzio University of Chieti-Pescara;
   University of L'Aquila
RP Ciancaglini, M (通讯作者)，Univ Aquila, Dept Life Hlth & Environm Sci, Eye Clin, I-67100 Laquila, Italy.
EM marco.ciancaglini@cc.univaq.it
RI Mastropasqua, Rodolfo/AAC-6453-2022; Agnifili, Luca/AAC-6345-2022
OI Ciancaglini, Marco/0000-0001-5888-7976; Agnifili,
   Luca/0000-0002-1625-6305; DI STASO, Silvio/0000-0001-7477-4939
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NR 17
TC 74
Z9 76
U1 1
U2 12
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 2015
VL 2015
AR 343515
DI 10.1155/2015/343515
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CT4BJ
UT WOS:000362750600001
PM 26491548
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Ferri, N
   Corsini, A
AF Ferri, Nicola
   Corsini, Alberto
TI Clinical evidence of statin therapy in non-dyslipidemic disorders
SO PHARMACOLOGICAL RESEARCH
LA English
DT Review
DE Statins; Rheumatoid arthritis; Venous thromboembolism; Liver diseases;
   Polycystic ovary syndrome; Macular degeneration
ID POLYCYSTIC-OVARY-SYNDROME; AGE-RELATED MACULOPATHY;
   RHEUMATOID-ARTHRITIS; VENOUS THROMBOEMBOLISM; CARDIOVASCULAR-DISEASE;
   TISSUE FACTOR; DIETARY-FAT; NONALCOHOLIC STEATOHEPATITIS;
   MYOCARDIAL-INFARCTION; REDUCTASE INHIBITORS
AB The clinical benefits of statins are strongly related to their low density lipoprotein cholesterol (LDL-C) lowering properties. However, considering that the pharmacological target of statins, the 3-hydroxy-3-methyl-3-glutaryl coenzyme A (HMG-CoA) reductase, is one of the upstream enzyme of the mevalonate pathway, its inhibition may determine a substantial impoverishment of additional lipid moieties required for a proper cellular function. From this hypothesis, several experimental and clinical evidences have been reported indicating additional effects of statins beyond the LDL-C lowering, in particular anti-inflammatory and immunomodulatory effects. Thus statin therapy, indicated for hyperlipidemic patients for primary and secondary prevention of coronary heart disease (CHD) has begun to be considered effective in other diseases not necessarily linked to altered lipid profile. In the present review we summarized the current clinical evidence of the efficacy and safety profile of statins in a variety of diseases, such as rheumatoid arthritis, venous thromboembolism, liver diseases, polycystic ovary syndrome, and age-related macular degeneration. As discussed in the review, pending large, well designed, randomized trials, it is reasonable to conclude that there is no definitive evidence for the use of statins in the aforementioned diseases. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Ferri, Nicola; Corsini, Alberto] Univ Milan, Dipartimento Sci Farmacol & Biomol, Milan, Italy.
C3 University of Milan
RP Ferri, N (通讯作者)，Dipartimento Sci Farmacol & Biomol, Via Balzaretti 9, I-20133 Milan, Italy.
EM nicola.ferri@unimi.it
RI ferri, nicola/K-7085-2019
OI ferri, nicola/0000-0001-8898-7441
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NR 125
TC 16
Z9 16
U1 0
U2 6
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-6618
J9 PHARMACOL RES
JI Pharmacol. Res.
PD OCT
PY 2014
VL 88
SI SI
BP 20
EP 30
DI 10.1016/j.phrs.2014.02.003
PG 11
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA AO6SO
UT WOS:000341482000004
PM 24548821
DA 2022-11-30
ER

PT J
AU Oladipupo, SS
   Smith, C
   Santeford, A
   Park, C
   Sene, A
   Wiley, LA
   Osei-Owusu, P
   Hsu, J
   Zapata, N
   Liu, F
   Nakamura, R
   Lavine, KJ
   Blumer, KJ
   Choi, K
   Apte, RS
   Ornitz, DM
AF Oladipupo, Sunday S.
   Smith, Craig
   Santeford, Andrea
   Park, Changwon
   Sene, Abdoulaye
   Wiley, Luke A.
   Osei-Owusu, Patrick
   Hsu, Joann
   Zapata, Nicole
   Liu, Fang
   Nakamura, Rei
   Lavine, Kory J.
   Blumer, Kendall J.
   Choi, Kyunghee
   Apte, Rajendra S.
   Ornitz, David M.
TI Endothelial cell FGF signaling is required for injury response but not
   for vascular homeostasis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE choroidal neovascularization; oxygen-induced retinopathy; retinopathy of
   prematurity; neoangiogenesis
ID FIBROBLAST-GROWTH-FACTOR; MURINE MODEL; EXPRESSION; INHIBITION; REPAIR;
   NEOVASCULARIZATION; OVEREXPRESSION; PROLIFERATION; RECEPTORS; PATHWAY
AB Endothelial cells (ECs) express fibroblast growth factor receptors (FGFRs) and are exquisitely sensitive to FGF signals. However, whether the EC or another vascular cell type requires FGF signaling during development, homeostasis, and response to injury is not known. Here, we show that Flk1-Cre or Tie2-Cre mediated deletion of FGFR1 and FGFR2 (Fgfr1/2(Flk1-Cre) or Fgfr1/2(Tie2-Cre) mice), which results in deletion in endothelial and hematopoietic cells, is compatible with normal embryonic development. As adults, Fgfr1/2(Flk1-Cre) mice maintain normal blood pressure and vascular reactivity and integrity under homeostatic conditions. However, neovascularization after skin or eye injury was significantly impaired in both Fgfr1/2(Flk1-Cre) and Fgfr1/2(Tie2-Cre) mice, independent of either hematopoietic cell loss of FGFR1/2 or vascular endothelial growth factor receptor 2 (Vegfr2) haploinsufficiency. Also, impaired neovascularization was associated with delayed cutaneous wound healing. These findings reveal a key requirement for cell-autonomous EC FGFR signaling in injuryinduced angiogenesis, but not for vascular homeostasis, identifying the EC FGFR signaling pathway as a target for diseases associated with aberrant vascular proliferation, such as age-related macular degeneration, and for modulating wound healing without the potential toxicity associated with direct manipulation of systemic FGF or VEGF activity.
C1 [Oladipupo, Sunday S.; Smith, Craig; Hsu, Joann; Lavine, Kory J.; Apte, Rajendra S.; Ornitz, David M.] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA.
   [Santeford, Andrea; Sene, Abdoulaye; Wiley, Luke A.; Zapata, Nicole; Nakamura, Rei; Apte, Rajendra S.] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA.
   [Park, Changwon; Liu, Fang; Choi, Kyunghee] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Osei-Owusu, Patrick; Blumer, Kendall J.] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA.
   [Lavine, Kory J.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); Washington
   University (WUSTL); Washington University (WUSTL); Washington University
   (WUSTL)
RP Apte, RS (通讯作者)，Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA.
EM apte@vision.wustl.edu; dornitz@wustl.edu
RI Osei-Owusu, Patrick/L-9104-2018; Osei-Owusu, Patrick/AAH-9063-2019;
   Sene, Abdoulaye/D-3342-2015
OI Sene, Abdoulaye/0000-0001-9194-7264; Wiley, Luke/0000-0003-0136-2364;
   Ornitz, David/0000-0003-1592-7629
FU National Institutes of Health (NIH) Grants [HL105732, T32-HL07275,
   HL63736, HL55337, EY019287]; NIH Vision Core Grant [P30EY02687]; Carl
   Marshall Reeves and Mildred Almen Reeves Foundation Inc. Award; Research
   to Prevent Blindness Inc. Career Development Award; International Retina
   Research Foundation; American Health Assistance Foundation; Thome
   Foundation; Lacy Foundation Research Award; Knights Templar Eye
   Foundation Grant; Research to Prevent Blindness Inc. Unrestricted Grant;
   Washington University Musculoskeletal Research Center (NIH Grant) [P30
   AR057235]; Digestive Disease Research Core Center (NIH Grant) [P30
   DK052574]; NATIONAL EYE INSTITUTE [P30EY002687, R01EY019287] Funding
   Source: NIH RePORTER; NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
   [K08HL123519, R01HL063736, R01HL055337, R01HL105732, R29HL055337]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ARTHRITIS AND
   MUSCULOSKELETAL AND SKIN DISEASES [P30AR057235] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY
   DISEASES [P30DK052574] Funding Source: NIH RePORTER; NATIONAL INSTITUTE
   OF GENERAL MEDICAL SCIENCES [R01GM044592] Funding Source: NIH RePORTER
FX We thank B. Coleman and M. Scott for help with tissue processing and the
   Mouse Genetics Core for technical help. This work was supported by
   National Institutes of Health (NIH) Grants HL105732 (to D.M.O.),
   T32-HL07275 (to S.S.O.), HL63736, HL55337 (to K. C.), and EY019287 (to
   R. S. A.), as well as NIH Vision Core Grant P30EY02687 and a Carl
   Marshall Reeves and Mildred Almen Reeves Foundation Inc. Award (to R. S.
   A.). This work was also supported by a Research to Prevent Blindness
   Inc. Career Development Award (to R. S. A.), International Retina
   Research Foundation (R. S. A.), American Health Assistance Foundation
   (R. S. A.), Thome Foundation (R. S. A.), a Lacy Foundation Research
   Award (to A. Santeford), a Knights Templar Eye Foundation Grant (to L.
   A. W.), and a Research to Prevent Blindness Inc. Unrestricted Grant to
   Washington University in St. Louis. Transgenic mouse production was made
   possible through the Washington University Musculoskeletal Research
   Center (NIH Grant P30 AR057235) and the Digestive Disease Research Core
   Center (NIH Grant P30 DK052574).
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NR 48
TC 90
Z9 92
U1 1
U2 20
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 16
PY 2014
VL 111
IS 37
BP 13379
EP 13384
DI 10.1073/pnas.1324235111
PG 6
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA AO8UH
UT WOS:000341630000042
PM 25139991
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Calzia, D
   Garbarino, G
   Caicci, F
   Manni, L
   Candiani, S
   Ravera, S
   Morelli, A
   Traverso, CE
   Panfoli, I
AF Calzia, Daniela
   Garbarino, Greta
   Caicci, Federico
   Manni, Lucia
   Candiani, Simona
   Ravera, Silvia
   Morelli, Alessandro
   Traverso, Carlo Enrico
   Panfoli, Isabella
TI Functional expression of electron transport chain complexes in mouse rod
   outer segments
SO BIOCHIMIE
LA English
DT Article
DE Electron transport chain protein; Retinal diseases; Retinal sections;
   Rod outer segments; Transmission electron microscopy
ID OXIDATIVE STRESS; MITOCHONDRIAL SUPEROXIDE; MACULAR DEGENERATION;
   RETINITIS-PIGMENTOSA; DNA MUTATION; OPTIC-NERVE; DAMAGE; METABOLISM;
   PHOTOTRANSDUCTION; LOCALIZATION
AB Rod photoreceptors efficiently carry out phototransduction cascade, an energetically costly process. Our recent data in bovine rod outer segment (OS) demonstrated that ATP for phototransduction is produced by an extramitochondrial oxidative phosphorylation, thanks to the expression of the Electron Transport Chain (ETC) complexes and of F1F0 ATP synthase in disks. Here we have focused on mouse retinas, reporting the activity of ETC complexes I, II, IV assayed directly on unfixed mouse eye sections, as well as immunogold TEM analysis of fixed mouse eye sections to verify the presence of ND4L subunit of ETC complex I and subunit IV of ETC complex IV in rod OS. Data suggest the presence of functional ETC in mouse rod OS, like their bovine counterpart. The protocol here developed for in situ assay of the ETC complexes activity represents a reliable method for the detection of ETC dysfunction in mice models of retinal pathologies. In fact, the ETC is a major source of reactive oxygen intermediates, and oxidative stress, especially when ectopically expressed in the OS. In turn, oxidative stress contributes to many retinal pathologies, such as diabetic retinopathy, age related macular degeneration, photoreceptor death after retinal detachment and some forms of retinitis pigmentosa.(C) 2014 Elsevier Masson SAS. All rights reserved.
C1 [Calzia, Daniela; Ravera, Silvia; Morelli, Alessandro; Panfoli, Isabella] Univ Genoa, DIFAR Biochem Lab, Dept Pharm, I-16132 Genoa, Italy.
   [Garbarino, Greta; Candiani, Simona] Univ Genoa, DISTAV, I-16132 Genoa, Italy.
   [Caicci, Federico; Manni, Lucia] Univ Padua, Dept Biol, I-35100 Padua, Italy.
   [Traverso, Carlo Enrico] Univ Genoa, DINOGMI, Clin Oculist, I-16132 Genoa, Italy.
C3 University of Genoa; University of Genoa; University of Padua;
   University of Genoa
RP Calzia, D (通讯作者)，Univ Genoa, DIFAR Biochem Lab, Viale Benedetto XV 3, I-16132 Genoa, Italy.
EM dcalzia@gmail.com
RI Ravera, Silvia/AAA-7982-2019; Panfoli, Isabella/X-1247-2019; Simona,
   Candiani/P-8640-2014
OI Ravera, Silvia/0000-0002-0803-1042; Panfoli,
   Isabella/0000-0002-6261-1128; Simona, Candiani/0000-0002-4453-5475;
   Manni, Lucia/0000-0003-4257-8946
FU University of Genoa [CUP D31J11001610005]
FX This work was supported by the Athenaeum Research Projects from
   University of Genoa [Grant CUP D31J11001610005] for IP.
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NR 59
TC 20
Z9 20
U1 0
U2 12
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI ISSY-LES-MOULINEAUX
PA 65 RUE CAMILLE DESMOULINS, CS50083, 92442 ISSY-LES-MOULINEAUX, FRANCE
SN 0300-9084
EI 1638-6183
J9 BIOCHIMIE
JI Biochimie
PD JUL
PY 2014
VL 102
BP 78
EP 82
DI 10.1016/j.biochi.2014.02.007
PG 5
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA AK7QU
UT WOS:000338623600009
PM 24565809
DA 2022-11-30
ER

PT J
AU Adhi, M
   Duker, JS
AF Adhi, Mehreen
   Duker, Jay S.
TI Optical coherence tomography - current and future applications
SO CURRENT OPINION IN OPHTHALMOLOGY
LA English
DT Review
DE applications of optical coherence tomography; chorioretinal diseases;
   retina; spectral-domain optical coherence tomography; swept-source
   optical coherence tomography
ID CENTRAL SEROUS CHORIORETINOPATHY; CHOROIDAL THICKNESS MEASUREMENTS;
   AGE-RELATED MACULOPATHY; RETINAL BLOOD-FLOW; MACULAR DEGENERATION;
   HIGH-SPEED; DIABETIC CHOROIDOPATHY; RETINITIS-PIGMENTOSA; LASER;
   REPRODUCIBILITY
AB Purpose of review
   Optical coherence tomography (OCT) has revolutionized the clinical practice of ophthalmology. It is a noninvasive imaging technique that provides high-resolution, cross-sectional images of the retina, retinal nerve fiber layer and the optic nerve head. This review discusses the present applications of the commercially available spectral-domain OCT (SD-OCT) systems in the diagnosis and management of retinal diseases, with particular emphasis on choroidal imaging. Future directions of OCT technology and their potential clinical uses are discussed.
   Recent findings
   Analysis of the choroidal thickness in healthy eyes and disease states such as age-related macular degeneration, central serous chorioretinopathy, diabetic retinopathy and inherited retinal dystrophies has been successfully achieved using SD-OCT devices with software improvements. Future OCT innovations such as longer-wavelength OCT systems including the swept-source technology, along with Doppler OCT and en-face imaging, may improve the detection of subtle microstructural changes in chorioretinal diseases by improving imaging of the choroid.
   Summary
   Advances in OCT technology provide for better understanding of pathogenesis, improved monitoring of progression and assistance in quantifying response to treatment modalities in diseases of the posterior segment of the eye. Further improvements in both hardware and software technologies should further advance the clinician's ability to assess and manage chorioretinal diseases.
C1 [Adhi, Mehreen; Duker, Jay S.] Tufts Med Ctr, New England Eye Ctr, Dept Ophthalmol, Boston, MA 02111 USA.
C3 Tufts Medical Center
RP Duker, JS (通讯作者)，Tufts Med Ctr, New England Eye Ctr, 800 Washington St, Boston, MA 02111 USA.
EM Jduker@tuftsmedicalcenter.org
RI Adhi, Mehreen/AAS-9733-2021
FU Carl Zeiss Meditech, Inc.; Optovue, Inc.; Research to Prevent Blindness
   Unrestricted grant; Tufts University School of Medicine; NIH
   [RO1-EY11289-23, R01-EY13178-07, R01-EY013516-07]; Massachusetts Lions
   Eye Research Fund; NATIONAL EYE INSTITUTE [R01EY013178, R01EY011289,
   R01EY013516] Funding Source: NIH RePORTER
FX J.S.D. receives research support from Carl Zeiss Meditech, Inc. and
   Optovue, Inc. This work was supported in part by a Research to Prevent
   Blindness Unrestricted grant to the New England Eye Center/Department of
   Ophthalmology, Tufts University School of Medicine, NIH contracts
   RO1-EY11289-23, R01-EY13178-07, R01-EY013516-07 and the Massachusetts
   Lions Eye Research Fund.
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NR 67
TC 342
Z9 358
U1 30
U2 237
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-8738
EI 1531-7021
J9 CURR OPIN OPHTHALMOL
JI Curr. Opin. Ophthalmol.
PD MAY
PY 2013
VL 24
IS 3
BP 213
EP 221
DI 10.1097/ICU.0b013e32835f8bf8
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 123ML
UT WOS:000317394000006
PM 23429598
OA Green Accepted
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Nakanishi, T
   Shimazawa, M
   Sugitani, S
   Kudo, T
   Imai, S
   Inokuchi, Y
   Tsuruma, K
   Hara, H
AF Nakanishi, Tomohiro
   Shimazawa, Masamitsu
   Sugitani, Sou
   Kudo, Takashi
   Imai, Shunsuke
   Inokuchi, Yuta
   Tsuruma, Kazuhiro
   Hara, Hideaki
TI Role of endoplasmic reticulum stress in light-induced photoreceptor
   degeneration in mice
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE endoplasmic reticulum; light damage; photoreceptor degeneration; retina
ID UNFOLDED PROTEIN RESPONSE; INDUCED RETINAL DAMAGE; ER STRESS;
   CELL-DEATH; MOLECULAR CHAPERONE; SIGNALING PATHWAY; PHOTIC INJURY;
   APOPTOSIS; MECHANISM; ACTIVATION
AB Exposure to excessive levels of light induces photoreceptor apoptosis and can be a causative factor in age-related macular degeneration (AMD). However, the cellular events that mediate this apoptotic response are poorly understood. Here, we investigated the roles of endoplasmic reticulum (ER) stress in light-induced cell death in the murine retina and murine photoreceptor cells (661W). Excessive light exposure induced retinal dysfunction, photoreceptor degeneration, and apoptosis. Furthermore, the accumulation of polyubiquitinated proteins and the transcriptional expression of ER stress-related factors, including 78-kDa glucose-regulated protein (GRP78)/immunoglobulin-binding protein (BiP) and C/EBP-homologous protein (CHOP), were increased in light-exposed retinas. Light exposure also induced both cell death and up-regulation of polyubiquitinated proteins, S-opsin aggregation, bip and chop mRNAs in 661W cells in vitro. Knock-down of chop mRNA inhibited photoreceptor cell death induced by light exposure. Furthermore, treatment with BiP inducer X (BIX), an ER stress inhibitor, induced bip mRNA and reduced both chop expression and light-induced photoreceptor cell death. These data indicate that excessive ER stress may induce photoreceptor cell death in light-exposed retinas via activation of the CHOP-dependent apoptotic pathway, suggesting that the ER stress may play a pivotal role in light exposure-induced retinal damage.
C1 [Nakanishi, Tomohiro; Shimazawa, Masamitsu; Sugitani, Sou; Imai, Shunsuke; Inokuchi, Yuta; Tsuruma, Kazuhiro; Hara, Hideaki] Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Gifu 5011196, Japan.
   [Kudo, Takashi] Osaka Univ, Grad Sch Med, Dept Psychiat, Osaka, Japan.
C3 Gifu Pharmaceutical University; Osaka University
RP Hara, H (通讯作者)，Gifu Pharmaceut Univ, Dept Biofunct Evaluat, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan.
EM hidehara@gifu-pu.ac.jp
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NR 62
TC 46
Z9 49
U1 4
U2 11
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD APR
PY 2013
VL 125
IS 1
BP 111
EP 124
DI 10.1111/jnc.12116
PG 14
WC Biochemistry & Molecular Biology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 112YR
UT WOS:000316631900012
PM 23216380
DA 2022-11-30
ER

PT J
AU Kieslich, CA
   Vazquez, H
   Goodman, GN
   Lopez de Victoria, A
   Morikis, D
AF Kieslich, Chris A.
   Vazquez, Homero
   Goodman, Gabrielle N.
   Lopez de Victoria, Aliana
   Morikis, Dimitrios
TI The effect of electrostatics on factor H function and related
   pathologies
SO JOURNAL OF MOLECULAR GRAPHICS & MODELLING
LA English
DT Article
DE Complement system; Factor H; C3b; Poisson-Boltzmann electrostatics;
   Electrostatic clustering
ID COMPLEMENT FACTOR-H; HEMOLYTIC-UREMIC SYNDROME; TRANSLATIONAL MINIREVIEW
   SERIES; DENSE DEPOSIT DISEASE; MACULAR DEGENERATION; BINDING-SITES;
   CONFORMATIONAL-CHANGES; MOLECULAR-DYNAMICS; FREE-ENERGIES; 2 PARTS
AB Factor H (FH) contributes to the regulation of the complement system by binding to polyanionic surfaces and the proteins C3b/C3c/C3d. This implicates charge and electrostatic interactions in recognition and binding of FH. Despite the large amount of experimental and pathology data the exact mechanism at molecular level is not yet known. We have implemented a computational framework for comparative analysis of the charge and electrostatic diversity of FH modules and C3b domains to identify electrostatic hotspots and predict potential binding sites. Our electrostatic potential clustering analysis shows that charge distributions and electrostatic potential distributions are more useful in understanding C3b-FH interactions than net charges alone. We present a model of non-specific electrostatic interactions of FH with polyanion-rich surfaces and specific interactions with C3b, using our computational data and existing experimental data. We discuss the electrostatic contributions to the formation of the C3b-FH complex and the competition between FH and Factor Bb (Bb) for binding to C3b. We also discuss the significance of mutations of charged amino acids in the pathobiology of FH-mediated disease, such as age-related macular degeneration, atypical hemolytic uremic syndrome, and dense deposit disease. Our data can be used to guide future experimental studies. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Kieslich, Chris A.; Vazquez, Homero; Goodman, Gabrielle N.; Lopez de Victoria, Aliana; Morikis, Dimitrios] Univ Calif Riverside, Dept Bioengn, Riverside, CA 92521 USA.
C3 University of California System; University of California Riverside
RP Morikis, D (通讯作者)，Univ Calif Riverside, Dept Bioengn, Riverside, CA 92521 USA.
EM dmorikis@engr.ucr.edu
RI Morikis, Dimitrios/L-8527-2013
OI Morikis, Dimitrios/0000-0003-0083-4665; Kieslich,
   Chris/0000-0002-1845-6589
FU TRDRP Dissertation Fellowship
FX C.A.K. would like to acknowledge the TRDRP Dissertation Fellowship for
   financial support.
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NR 65
TC 11
Z9 11
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1093-3263
J9 J MOL GRAPH MODEL
JI J. Mol. Graph.
PD AUG
PY 2011
VL 29
IS 8
BP 1047
EP 1055
DI 10.1016/j.jmgm.2011.04.010
PG 9
WC Biochemical Research Methods; Biochemistry & Molecular Biology; Computer
   Science, Interdisciplinary Applications; Crystallography; Mathematical &
   Computational Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Computer Science; Crystallography;
   Mathematical & Computational Biology
GA 789RM
UT WOS:000292534000009
PM 21605993
DA 2022-11-30
ER

PT J
AU Penha, FM
   Rodrigues, EB
   Furlani, BA
   Dib, E
   Melo, GB
   Farah, ME
AF Penha, Fernando M.
   Rodrigues, Eduardo B.
   Furlani, Bruno A.
   Dib, Eduardo
   Melo, Gustavo B.
   Farah, Michel E.
TI Toxicological considerations for intravitreal drugs
SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
LA English
DT Review
DE bevacizumab; corticosteroids; monoclonal antibodies; ranibizumab;
   retina; retinal pharmacotherapy; triamcinolone; tumor necrosis factor;
   vascular endothelial growth factor; VEGF-trap
ID RETINA STUDY-GROUP; OIL-FILLED EYE; MACULAR DEGENERATION; TRIAMCINOLONE
   ACETONIDE; CHOROIDAL NEOVASCULARIZATION; BEVACIZUMAB AVASTIN; IN-VITRO;
   RABBIT EYES; FUNGAL ENDOPHTHALMITIS; POTENT ANTITUMOR
AB Introduction: Intravitreal injections are a very common procedure and are the most effective route of drug delivery to the retina. There are currently several drugs available and even more are in development; therefore, safety is a very important concern.
   Areas covered: The toxicological considerations of the most common drugs used for intravitreal pharmacotherapy such as anti-VEGFs, corticosteroids and antibiotics. Emerging agents such as anti-TNFs, VEGF-trap and kinase inhibitors are also discussed. An assessment of the efficacy and safety issues of the most relevant drugs including bevacizumab, ranibizumab and triamcinolone is presented.
   Expert opinion: The toxicology and safety profiles are available for several drugs that are either in use or will be available for intravitreal injections. Retinal pharmacotherapy is very effective for different retinal diseases; however safety is a very important issue when intravitreal injections are applied and the possibility of retinal toxicity should always be kept in mind. Bevacizumab and ranibizumab are effective for the therapy of wet-age-related macular degeneration and macular edema, while triamcinolone remains an alternative agent to treat secondary macular edema. It is important, as some of these drugs will be used for extended periods of time, that their long-term toxicological effects are better understood.
C1 [Penha, Fernando M.; Rodrigues, Eduardo B.; Furlani, Bruno A.; Dib, Eduardo; Melo, Gustavo B.; Farah, Michel E.] Univ Fed Sao Paulo, Dept Ophthalmol, Vis Inst, BR-88025080 Florianopolis, SC, Brazil.
C3 Universidade Federal de Sao Paulo (UNIFESP)
RP Penha, FM (通讯作者)，Univ Fed Sao Paulo, Dept Ophthalmol, Vis Inst, Emilio Fernandes Schoroeder 111, BR-88025080 Florianopolis, SC, Brazil.
EM penhaepm@yahoo.com.br
RI Penha, Fernando M/G-1784-2012; Melo, Gustavo/AAD-3844-2019; Farah,
   Michel Eid E/F-3285-2012
OI Melo, Gustavo/0000-0001-5765-2008; Farah, Michel Eid
   E/0000-0001-5951-0193; Penha, Fernando/0000-0002-1038-5472; Buchele
   Rodrigues, Eduardo/0000-0002-4224-0921
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NR 103
TC 15
Z9 16
U1 1
U2 4
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1742-5255
EI 1744-7607
J9 EXPERT OPIN DRUG MET
JI Expert Opin. Drug Metab. Toxicol.
PD AUG
PY 2011
VL 7
IS 8
BP 1021
EP 1034
DI 10.1517/17425255.2011.585970
PG 14
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
GA 793RF
UT WOS:000292840100007
PM 21627546
DA 2022-11-30
ER

PT J
AU Dhingra, N
   Kelly, S
   Majid, MA
   Bailey, CB
   Dick, AD
AF Dhingra, Narendra
   Kelly, Susan
   Majid, Mohammed A.
   Bailey, Claire B.
   Dick, Andrew D.
TI Inflammatory choroidal neovascular membrane in posterior
   uveitis-pathogenesis and treatment
SO INDIAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Review
DE Choroidal neovascular membrane; immunosuppression; photodynamic therapy;
   posterior segment intraocular inflammation; posterior uveitis
ID PUNCTATE INNER CHOROIDOPATHY; INTRAVITREAL BEVACIZUMAB AVASTIN; OCULAR
   HISTOPLASMOSIS SYNDROME; EPITHELIUM-DERIVED FACTOR; PHOTODYNAMIC
   THERAPY; MULTIFOCAL CHOROIDITIS; DEFICIENT MICE; SUBFOVEAL;
   CORTICOSTEROIDS; COMPLEMENT
AB Choroidal neovascular membrane (CNVM) formation is a well-documented sight-threatening complication of posterior segment intraocular inflammation (PSII). The aim of this article is to review the basic and clinical science literature on the pathogenesis of CNVM formation in PSII and to present results of a case series. We searched the literature using the mesh terms- inflammation, CNVM, age-related macular degeneration, immunosuppression, photodynamic therapy, steroids, vascular endothelial growth factors and posterior uveitis. Additionally, we evaluated the visual outcome of and clinical response to our standard treatment protocol involving a combination treatment for young patients with inflammatory CNVM. The development of CNVM in PSII is promulgated by infiltrating myeloid cells as well as choroidal and retinal myeloid cell activation, subsequent vascular endothelial growth factors, cytokine and chemokine production and complement activation acting in consort to mediate angiogenic responses. No clear standard of care currently exists for the treatment of inflammatory CNVM and various combinations have been tried. Using our combination treatment, visual acuity improved in four, stabilized in one and worsened in four patients. Though significant advances have occurred in the understanding of the pathogenesis and management of this condition, optimizing therapeutic regimens will require further well-constructed prospective cohort series.
C1 [Dhingra, Narendra; Kelly, Susan; Majid, Mohammed A.; Bailey, Claire B.; Dick, Andrew D.] Bristol Eye Hosp, Dept Acad Ophthalmol, Bristol BS1 2LX, Avon, England.
C3 Bristol Eye Hospital
RP Dhingra, N (通讯作者)，Bristol Eye Hosp, Dept Acad Ophthalmol, Lower Maudlin St, Bristol BS1 2LX, Avon, England.
EM ndhingra@doctors.org.uk
OI Dick, Andrew/0000-0002-0742-3159
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NR 51
TC 36
Z9 36
U1 0
U2 3
PU WOLTERS KLUWER MEDKNOW PUBLICATIONS
PI MUMBAI
PA WOLTERS KLUWER INDIA PVT LTD , A-202, 2ND FLR, QUBE, C T S  NO 1498A-2
   VILLAGE MAROL, ANDHERI EAST, MUMBAI, 400059, INDIA
SN 0301-4738
EI 1998-3689
J9 INDIAN J OPHTHALMOL
JI Indian J. Ophthalmol.
PD JAN-FEB
PY 2010
VL 58
IS 1
BP 3
EP 10
DI 10.4103/0301-4738.58467
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 538GK
UT WOS:000273172300002
PM 20029141
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Mac Gabhann, F
   Demetriades, AM
   Deering, T
   Packer, JD
   Shah, SM
   Duh, E
   Campochiaro, PA
   Popel, AS
AF Mac Gabhann, Feilim
   Demetriades, Anna Maria
   Deering, Tye
   Packer, Jonathan D.
   Shah, Syed Mahmood
   Duh, Elia
   Campochiaro, Peter A.
   Popel, Aleksander S.
TI Protein transport to choroid and retina following periocular injection:
   Theoretical and experimental study
SO ANNALS OF BIOMEDICAL ENGINEERING
LA English
DT Article
DE drug delivery; mathematical model; angiogenesis; anti-angiogenic drug;
   green fluorescent protein; diffusion
ID INTERSTITIAL VOLUME FRACTION; GREEN FLUORESCENT PROTEIN; PIGMENT
   EPITHELIUM; MOLECULAR-WEIGHT; BRUCHS MEMBRANE; DRUG-DELIVERY;
   SURFACE-AREA; SCLERA; PERMEABILITY; DIFFUSION
AB Ocular neovascularization is a major cause of blindness in several diseases including age-related macular degeneration (choroidal neovascularization) and diabetic retinopathy (retinal neovascularization). Antiangiogenic agents with clinically significant effects exist, but a key question remains: how to effectively deliver drugs to the site of neovascularization. Periocular delivery of drugs or proteins is less invasive and safer than intravitreous delivery, but little is known regarding how and to what extent agents access intraocular tissues after periocular injection. We present a computational model of drug or protein transport into the eye following periocular injection to quantify movement of macromolecules across the sclera of the mouse eye. We apply this model to the movement of green fluorescent protein (GFP) across the mouse eye and fit the results of in vivo experiments to find transport parameters. Using these parameters, the model gives the profile of interstitial GFP concentration across the sclera, choroid and retina. We compare this to predictions of transport following intravitreous injections. We then scale up the model to estimate the transport of GFP into the human choroid and retina; the thicker sclera decreases transscleral delivery. This is the first model of ocular drug delivery to explicitly account for transport properties of each eye layer.
C1 Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA.
   Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD USA.
C3 Johns Hopkins University; Johns Hopkins University; Johns Hopkins
   Medicine
RP Mac Gabhann, F (通讯作者)，Johns Hopkins Univ, Sch Med, Dept Biomed Engn, 720 Rutland Ave 613 Traylor, Baltimore, MD 21205 USA.
EM feilim@jhu.edu
RI Mac Gabhann, Feilim/A-3436-2010; Popel, Aleksander S/A-6724-2009
OI Mac Gabhann, Feilim/0000-0003-3481-7740; Popel,
   Aleksander/0000-0002-6706-9235
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NR 35
TC 20
Z9 20
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013 USA
SN 0090-6964
J9 ANN BIOMED ENG
JI Ann. Biomed. Eng.
PD APR
PY 2007
VL 35
IS 4
BP 615
EP 630
DI 10.1007/s10439-006-9238-x
PG 16
WC Engineering, Biomedical
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering
GA 148MH
UT WOS:000245078300010
PM 17277991
DA 2022-11-30
ER

PT J
AU Ha, KN
   Chen, Y
   Cai, JY
   Sternberg, P
AF Ha, Khoi-Nguyen
   Chen, Yan
   Cai, Jiyang
   Sternberg, Paul, Jr.
TI Increased glutathione synthesis through an ARE-Nrf2-dependent pathway by
   zinc in the RPE: Implication for protection against oxidative stress
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID PIGMENT EPITHELIAL-CELLS; LIPID-PEROXIDATION; GENE-EXPRESSION; DAMAGE;
   PATHOGENESIS; DEFICIENCY; INDUCTION; TOXICITY; STORAGE; LIVER
AB PURPOSE. To determine the molecular mechanisms underlying the protective effects of zinc against oxidative stress in cultured retinal pigment epithelial (RPE) cells.
   METHODS. Cultured ARPE-19 cells were treated with different concentrations of zinc for various times. Cellular glutathione (GSH) and glutathione disulfide (GSSG) levels were measured by high-performance liquid chromatography (HPLC). Glutamate-cysteine ligase (GCL) expression was measured by quantitative reverse transcription-PCR (RT-PCR). Nuclear factor er throid2-related factor (Nrf2) activity was measured in a dual luciferase assay after transfection of reporter plasmids containing the antioxidant response element (ARE). The small interference (si)RNA approach was used to knock down the expression of Nrf2.
   RESULTS. Zinc significantly increased GSH levels in It ARPE-19 cells through induction of the de novo synthesis pathway. At 150 mu M, zinc increased the GSH level by 70%. At similar concentrations, zinc upregulated the mRNA level of GCL and activated the ARE-Nrf2 pathway. The effects of zinc on ARE activation and GSH synthesis were inhibited by knockdown of Nrf2 expression using the siRNA approach.
   CONCLUSIONS. Induction of the ARE-Nrf2 pathway by zinc provides powerful and prolonged antioxidation and detoxification that may explain the beneficial effects of zinc observed in the treatment of age-related macular degeneration
C1 Vanderbilt Univ, Dept Ophthalmol & Visual Sci, Sch Med, Nashville, TN 37232 USA.
C3 Vanderbilt University
RP Sternberg, P (通讯作者)，Vanderbilt Univ, Dept Ophthalmol & Visual Sci, Sch Med, 8000 Med Ctr E,N Tower, Nashville, TN 37232 USA.
EM paul.sternberg@vanderbilt.edu
FU NATIONAL EYE INSTITUTE [R29EY007892, R01EY007892, P30EY008126] Funding
   Source: NIH RePORTER; NEI NIH HHS [EY08126, EY07892] Funding Source:
   Medline
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NR 45
TC 119
Z9 124
U1 0
U2 10
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUN
PY 2006
VL 47
IS 6
BP 2709
EP 2715
DI 10.1167/iovs.05-1322
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 048LQ
UT WOS:000237949000060
PM 16723490
DA 2022-11-30
ER

PT J
AU Lee, CJ
   Vroom, JA
   Fishman, HA
   Bent, SF
AF Lee, CJ
   Vroom, JA
   Fishman, HA
   Bent, SF
TI Determination of human lens capsule permeability and its feasibility as
   a replacement for Bruch's membrane
SO BIOMATERIALS
LA English
DT Article
DE diffusion coefficient; retina; lens capsule; dextran; membrane
ID RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; TRANSPLANTATION; AGE;
   DIFFUSION; CELLS; TRANSPORT; SUPPORT; SCLERA; EYE
AB We have investigated human anterior lens capsule as a potential replacement for Bruch's membrane as a treatment for age-related macular degeneration. Any substrate to replace Bruch's membrane should possess certain characteristics to maintain proper function of the overlying retina. One of the important properties of Bruch's membrane is allowing the flow of nutrients and waste between the retinal pigment epithelium and the choriocapillaris. Here, we measured the permeability of the lens capsule by studying the diffusion of various molecular weight FITC-dextran molecules. Expressions for extraction of diffusion coefficients from concentration vs. time data from a blind-well chamber apparatus were derived for both a single and double membrane experiments. The diffusion coefficients in the lens capsule were found to be in the range of 10(-6) to 10(-10) cm(2)/s. We demonstrated a power law relationship, with the diffusion coefficient possessing a -0.6 order dependence on molecular weight. The molecular weight exclusion limit was determined to be 150 +/- 40kDa. We have compared this value with reported values of Bruch's membrane molecular weight exclusion limit and find that the lens capsule has the potential to act as a substitute Bruch's membrane. (c) 2005 Elsevier Ltd. All rights reserved.
C1 Stanford Univ, Dept Chem Engn, Stanford, CA 94305 USA.
   Stanford Univ, Sch Med, Dept Ophthalmol, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University
RP Bent, SF (通讯作者)，Stanford Univ, Dept Chem Engn, Stanford, CA 94305 USA.
EM bent@stanford.edu
OI Bent, Stacey/0000-0002-1084-5336
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NR 28
TC 51
Z9 61
U1 0
U2 10
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 MAR
PY 2006
VL 27
IS 8
BP 1670
EP 1678
DI 10.1016/j.biomaterials.2005.09.008
PG 9
WC Engineering, Biomedical; Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Materials Science
GA 004DJ
UT WOS:000234731900055
PM 16199085
DA 2022-11-30
ER

PT J
AU Amar, I
   Aserin, A
   Garti, N
AF Amar, I
   Aserin, A
   Garti, N
TI Solubilization patterns of lutein and lutein esters in food grade
   nonionic microemulsions
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE lutein; microemulsion; solubilization; nonionic emulsifier
ID CAROTENOIDS; DELIVERY
AB Lutein, a naturally occurring carotenoid, is widely distributed in fruits and vegetables and is particularly concentrated in the Tagetes erecta flower. Epidemiological studies suggest that a high lutein intake (6 mg/day) increases serum levels that are associated with a lower risk of cataract and age-related macular degeneration. Lutein can either be free or esterified (myristate, palmitate, or stearate). Both are practically insoluble in aqueous systems, and their solubility in food grade solvents (oils) is very limited, resulting is low bioavailability. To improve its solubility and bioavailability, lutein was solubilized in U-type food grade microemulsions based on ethoxylated sorbitan fatty acid esters, glycerol, R-(+)-limonene, and ethanol. Some of the main findings are as follows: (1) reverse micellar and W/O compositions solubilized both luteins better than an O/W microemulsion, and maximum solubilization is obtained within the bicontinuous phase; (2) free lutein is solubilized better than the esterified one, in the W/O microemulsions, whereas the esterified lutein is better accommodated within the O/W microemulsion; (3) vegetable oils decrease the solubilization of free lutein; (4) glycerol and alcohol enhance the solubilization of both luteins; (5) solubilization is surfactant-dependent in all mesophase structures, but its strongest effect is in the bicontinuous phase.
C1 Hebrew Univ Jerusalem, Casali Inst Appl Chem, IL-91904 Jerusalem, Israel.
C3 Hebrew University of Jerusalem
RP Garti, N (通讯作者)，Hebrew Univ Jerusalem, Casali Inst Appl Chem, Givat Ram Campus, IL-91904 Jerusalem, Israel.
EM garti@vms.huji.ac.il
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NR 12
TC 82
Z9 90
U1 4
U2 60
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0021-8561
EI 1520-5118
J9 J AGR FOOD CHEM
JI J. Agric. Food Chem.
PD JUL 30
PY 2003
VL 51
IS 16
BP 4775
EP 4781
DI 10.1021/jf026222t
PG 7
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
   Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Agriculture; Chemistry; Food Science & Technology
GA 704TR
UT WOS:000184356700043
PM 14705912
DA 2022-11-30
ER

PT J
AU McDonald, DM
   Choyke, PL
AF McDonald, DM
   Choyke, PL
TI Imaging of angiogenesis: from microscope to clinic
SO NATURE MEDICINE
LA English
DT Review
ID ENDOTHELIAL GROWTH-FACTOR; HUMAN BREAST-CANCER; ULTRASOUND CONTRAST
   AGENTS; IN-VIVO ASSESSMENT; MICROVESSEL DENSITY; VASCULAR-PERMEABILITY;
   TUMOR VASCULARITY; BLOOD-VESSELS; CELL PROLIFERATION; PROSTATE-CANCER
AB Advances in imaging are transforming our understanding of angiogenesis and the evaluation of drugs that stimulate or inhibit angiogenesis in preclinical models and human disease. Vascular imaging makes it possible to quantify the number and spacing of blood vessels, measure blood flow and vascular permeability, and analyze cellular and molecular abnormalities in blood vessel walls. Microscopic methods ranging from fluorescence, confocal and multiphoton microscopy to electron microscopic imaging are particularly useful for elucidating structural and functional abnormalities of angiogenic blood vessels. Magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), ultrasonography and optical imaging provide noninvasive, functionally relevant images of angiogenesis in animals and humans. An ongoing dilemma is, however, that microscopic methods provide their highest resolution on preserved tissue specimens, whereas clinical methods give images of living tissues deep within the body but at much lower resolution and specificity and generally cannot resolve vessels of the microcirculation. Future challenges include developing new imaging methods that can bridge this resolution gap and specifically identify angiogenic vessels. Another goal is to determine which microscopic techniques are the best benchmarks for interpreting clinical images. The importance of angiogenesis in cancer, chronic inflammatory diseases, age-related macular degeneration and reversal of ischemic heart and limb disease provides incentive for meeting these challenges.
C1 Univ Calif San Francisco, Ctr Comprehens Canc, Cardiovasc Res Inst, San Francisco, CA 94143 USA.
   Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA.
   NIH, Imaging Sci Program, Bethesda, MD 20892 USA.
C3 University of California System; University of California San Francisco;
   UCSF Medical Center; UCSF Helen Diller Family Comprehensive Cancer
   Center; University of California System; University of California San
   Francisco; National Institutes of Health (NIH) - USA
RP McDonald, DM (通讯作者)，Univ Calif San Francisco, Ctr Comprehens Canc, Cardiovasc Res Inst, 513 Parnassus Ave, San Francisco, CA 94143 USA.
EM dmcd@itsa.ucsf.edu; pchoyke@nih.gov
FU NATIONAL CANCER INSTITUTE [P50CA090270] Funding Source: NIH RePORTER;
   NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL024136, R01HL059157]
   Funding Source: NIH RePORTER; NCI NIH HHS [P50-CA90270] Funding Source:
   Medline; NHLBI NIH HHS [HL-59157, HL-24136] Funding Source: Medline
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NR 140
TC 774
Z9 806
U1 4
U2 209
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD JUN
PY 2003
VL 9
IS 6
BP 713
EP 725
DI 10.1038/nm0603-713
PG 13
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA 688PH
UT WOS:000183444100026
PM 12778170
DA 2022-11-30
ER

PT J
AU Chen, LS
   Perera, ND
   Karoukis, AJ
   Feathers, KL
   Ali, RR
   Thompson, DA
   Fahim, AT
AF Chen, Lisheng
   Perera, N. Dayanthi
   Karoukis, Athanasios J.
   Feathers, Kecia L.
   Ali, Robin R.
   Thompson, Debra A.
   Fahim, Abigail T.
TI Oxidative stress differentially impacts apical and basolateral secretion
   of angiogenic factors from human iPSC-derived retinal pigment epithelium
   cells
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MACULAR DEGENERATION; SUSCEPTIBILITY; INHIBITOR; TIMP3
AB The retinal pigment epithelium (RPE) is a polarized monolayer that secretes growth factors and cytokines towards the retina apically and the choroid basolaterally. Numerous RPE secreted proteins have been linked to the pathogenesis of age-related macular degeneration (AMD). The purpose of this study was to determine the differential apical and basolateral secretome of RPE cells, and the effects of oxidative stress on directional secretion of proteins linked to AMD and angiogenesis. Tandem mass tag spectrometry was used to profile proteins in human iPSC-RPE apical and basolateral conditioned media. Changes in secretion after oxidative stress induced by H2O2 or tert-butyl hydroperoxide (tBH) were investigated by ELISA and western analysis. Out of 926 differentially secreted proteins, 890 (96%) were more apical. Oxidative stress altered the secretion of multiple factors implicated in AMD and neovascularization and promoted a pro-angiogenic microenvironment by increasing the secretion of pro-angiogenic molecules (VEGF, PTN, and CRYAB) and decreasing the secretion of anti-angiogenic molecules (PEDF and CFH). Apical secretion was impacted more than basolateral for PEDF, CRYAB and CFH, while basolateral secretion was impacted more for VEGF, which may have implications for choroidal neovascularization. This study lays a foundation for investigations of dysfunctional RPE polarized protein secretion in AMD and other chorioretinal degenerative disorders.
C1 [Chen, Lisheng; Perera, N. Dayanthi; Karoukis, Athanasios J.; Feathers, Kecia L.; Ali, Robin R.; Thompson, Debra A.; Fahim, Abigail T.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA.
   [Ali, Robin R.] KCL Ctr Cell & Gene Therapy, London WC2R 2LS, England.
   [Thompson, Debra A.] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48105 USA.
C3 University of Michigan System; University of Michigan; University of
   Michigan System; University of Michigan
RP Fahim, AT (通讯作者)，Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA.
EM ahteich@med.umich.edu
FU National Eye Institute [K12EY022299, 1K08EY032991, P30 EY007003];
   Choroideremia Research Foundation award; Eversight Vision award;
   Research to Prevent Blindness
FX Dr. Fahim was supported by a National Eye Institute K12 award
   (K12EY022299) and K08 award (1K08EY032991), a Choroideremia Research
   Foundation award, an Eversight Vision award, and an unrestricted grant
   from Research to Prevent Blindness. This work utilized the Vision
   Research Core funded by P30 EY007003 from the National Eye Institute.
   The content is solely the responsibility of the authors and does not
   necessarily represent the official views of the National Institutes of
   Health. We thank Patrice Fort, PhD, for the CRYAB antibody.
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NR 38
TC 0
Z9 0
U1 1
U2 1
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUL 26
PY 2022
VL 12
IS 1
AR 12694
DI 10.1038/s41598-022-16701-6
PG 13
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 3L8HT
UT WOS:000835004100006
PM 35882889
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Bobadilla, M
   Pariente, A
   Oca, AI
   Pelaez, R
   Perez-Sala, A
   Larrayoz, IM
AF Bobadilla, Miriam
   Pariente, Ana
   Oca, Ana, I
   Pelaez, Rafael
   Perez-Sala, Alvaro
   Larrayoz, Ignacio M.
TI Biomarkers as Predictive Factors of Anti-VEGF Response
SO BIOMEDICINES
LA English
DT Review
DE age-related macular degeneration; ranibizumab; aflibercept;
   brolucizumab; anti-VEGF; SNPs; microRNAs; proteomic; metabolomic;
   antiangiogenic therapy
ID ENDOTHELIAL GROWTH-FACTOR; COMPLEMENT FACTOR-H; INTRAVITREAL RANIBIZUMAB
   TREATMENT; ANGIOPOIETIN-LIKE 4; MACULAR DEGENERATION; RISK-FACTORS;
   FACTOR-B; GENE POLYMORPHISMS; AQUEOUS-HUMOR; COMPONENT 2
AB Age-related macular degeneration is the main cause of irreversible vision in developed countries, and intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are the current gold standard treatment today. Although anti-VEGF treatment results in important improvements in the course of this disease, there is a considerable number of patients not responding to the standardized protocols. The knowledge of how a patient will respond or how frequently retreatment might be required would be vital in planning treatment schedules, saving both resource utilization and financial costs, but today, there is not an ideal biomarker to use as a predictive response to ranibizumab therapy. Whole blood and blood mononuclear cells are the samples most studied; however, few reports are available on other important biofluid samples for studying this disease, such as aqueous humor. Moreover, the great majority of studies carried out to date were focused on the search for SNPs in genes related to AMD risk factors, but miRNAs, proteomic and metabolomics studies have rarely been conducted in anti-VEGF-treated samples. Here, we propose that genomic, proteomic and/or metabolomic markers could be used not alone but in combination with other methods, such as specific clinic characteristics, to identify patients with a poor response to anti-VEGF treatment to establish patient-specific treatment plans.
C1 [Bobadilla, Miriam; Pariente, Ana; Oca, Ana, I; Pelaez, Rafael; Perez-Sala, Alvaro; Larrayoz, Ignacio M.] Neurodegenerat Dis Area Ctr Biomed Res La Rioja, CIBIR, Biomarkers & Mol Signaling Grp, Logrono 26006, Spain.
   [Larrayoz, Ignacio M.] Univ La Rioja, Dept Nursing, GRUPAC, Duquesa de La Victoria 88, Logrono 26006, Spain.
C3 Universidad de La Rioja
RP Larrayoz, IM (通讯作者)，Neurodegenerat Dis Area Ctr Biomed Res La Rioja, CIBIR, Biomarkers & Mol Signaling Grp, Logrono 26006, Spain.; Larrayoz, IM (通讯作者)，Univ La Rioja, Dept Nursing, GRUPAC, Duquesa de La Victoria 88, Logrono 26006, Spain.
EM mbobadilla@riojasalud.es; apariente@riojasalud.es; aioca@riojasalud.es;
   rpelaez@riojasalud.es; aperez@riojasalud.es; ilarrayoz@riojasalud.es
RI Larrayoz, Ignacio M/I-5613-2012; Bobadilla, Miriam/H-9780-2015
OI Larrayoz, Ignacio M/0000-0003-1629-152X; Bobadilla,
   Miriam/0000-0002-7719-3483; Pariente Delgado, Ana/0000-0001-9046-6629;
   Pelaez, Rafael/0000-0002-4047-6017
FU Instituto de Salud Carlos III [PI19/01805, CPII20/00029]; Fundacion
   Rioja Salud; European Regional Development Fund (ERDF) "A way to build
   Europe"; European Social fund (ESF) "Investing in your future"
FX This research was funded, in part, by a grant (PI19/01805) from the
   Instituto de Salud Carlos III, co-funded by European Regional
   Development Fund (ERDF) "A way to build Europe" and by Fundacion Rioja
   Salud. I.M.L. was supported by a Miguel Servet contract (CPII20/00029)
   from the Instituto de Salud Carlos III, co-funded by European Social
   fund (ESF) "Investing in your future".
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NR 170
TC 1
Z9 1
U1 3
U2 3
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2227-9059
J9 BIOMEDICINES
JI Biomedicines
PD MAY
PY 2022
VL 10
IS 5
AR 1003
DI 10.3390/biomedicines10051003
PG 23
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental;
   Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Research & Experimental Medicine;
   Pharmacology & Pharmacy
GA 1R2ZJ
UT WOS:000803242900001
PM 35625740
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Lyu, YF
   Zauhar, R
   Dana, N
   Strang, CE
   Hu, J
   Wang, K
   Liu, SR
   Pan, NF
   Gamlin, P
   Kimble, JA
   Messinger, JD
   Curcio, CA
   Stambolian, D
   Li, MY
AF Lyu, Yafei
   Zauhar, Randy
   Dana, Nicholas
   Strang, Christianne E.
   Hu, Jian
   Wang, Kui
   Liu, Shanrun
   Pan, Naifei
   Gamlin, Paul
   Kimble, James A.
   Messinger, Jeffrey D.
   Curcio, Christine A.
   Stambolian, Dwight
   Li, Mingyao
TI Implication of specific retinal cell-type involvement and gene
   expression changes in AMD progression using integrative analysis of
   single-cell and bulk RNA-seq profiling
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MACULAR DEGENERATION; RETINITIS-PIGMENTOSA; AGE; MICROGLIA; EYES;
   COMPLEMENT; MODELS; C3
AB Y Age-related macular degeneration (AMD) is a blinding eye disease with no unifying theme for its etiology. We used single-cell RNA sequencing to analyze the transcriptomes of similar to 93,000 cells from the macula and peripheral retina from two adult human donors and bulk RNA sequencing from fifteen adult human donors with and without AMD. Analysis of our single-cell data identified 267 cell-type-specific genes. Comparison of macula and peripheral retinal regions found no cell-type differences but did identify 50 differentially expressed genes (DEGs) with about 1/3 expressed in cones. Integration of our single-cell data with bulk RNA sequencing data from normal and AMD donors showed compositional changes more pronounced in macula in rods, microglia, endothelium, Muller glia, and astrocytes in the transition from normal to advanced AMD. KEGG pathway analysis of our normal vs. advanced AMD eyes identified enrichment in complement and coagulation pathways, antigen presentation, tissue remodeling, and signaling pathways including PI3K-Akt, NOD-like, Toll-like, and Rap1. These results showcase the use of single-cell RNA sequencing to infer cell-type compositional and cell-type-specific gene expression changes in intact bulk tissue and provide a foundation for investigating molecular mechanisms of retinal disease that lead to new therapeutic targets.
C1 [Lyu, Yafei; Hu, Jian; Wang, Kui; Li, Mingyao] Univ Penn, Dept Biostat Epidemiol & Informat, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Zauhar, Randy] Univ Sci Philadelphia, Dept Chem & Biochem, Philadelphia, PA 19104 USA.
   [Dana, Nicholas; Stambolian, Dwight] Univ Penn, Dept Ophthalmol, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Dana, Nicholas; Stambolian, Dwight] Univ Penn, Dept Human Genet, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Strang, Christianne E.] Univ Alabama Birmingham, Dept Psychol, Birmingham, AL 35294 USA.
   [Wang, Kui] Nankai Univ, Sch Math Sci, Dept Informat Theory & Data Sci, Tianjin 30071, Peoples R China.
   [Wang, Kui] Nankai Univ, LPMC, Tianjin 30071, Peoples R China.
   [Liu, Shanrun] Univ Alabama Birmingham, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA.
   [Pan, Naifei] Univ Penn, Dept Comp & Informat Sci, Philadelphia, PA 19104 USA.
   [Gamlin, Paul; Kimble, James A.; Messinger, Jeffrey D.; Curcio, Christine A.] Univ Alabama Birmingham, Dept Ophthalmol & Visual Sci, Birmingham, AL 35294 USA.
C3 University of Pennsylvania; Pennsylvania Medicine; University of
   Pennsylvania; Pennsylvania Medicine; University of Pennsylvania;
   Pennsylvania Medicine; University of Alabama System; University of
   Alabama Birmingham; Nankai University; Nankai University; University of
   Alabama System; University of Alabama Birmingham; University of
   Pennsylvania; University of Alabama System; University of Alabama
   Birmingham
RP Li, MY (通讯作者)，Univ Penn, Dept Biostat Epidemiol & Informat, Perelman Sch Med, Philadelphia, PA 19104 USA.; Stambolian, D (通讯作者)，Univ Penn, Dept Ophthalmol, Perelman Sch Med, Philadelphia, PA 19104 USA.; Stambolian, D (通讯作者)，Univ Penn, Dept Human Genet, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM stamboli@pennmedicine.upenn.edu; mingyao@pennmedicine.upenn.edu
FU Macula Vision Research Foundation [R01GM125301, R21EY031877,
   R01EY030192, R01EY031209, P30 EY003039]; SupportSight Foundation (TSSF);
   Macula Vision Research Foundation; Arnold and Mabel Beckman Initiative
   for Macular Research
FX This work was supported by the following grants: R01GM125301 (M.L.),
   R21EY031877 (M.L), P30 EY003039 (UAB), R01EY030192 (M.L. and D.S.),
   R01EY031209 (D.S. and M.L.), and Macula Vision Research Foundation
   (D.S.) and SupportSight Foundation (TSSF) (D.S.). We thank the UAB
   comprehensive flow cytometry core for their services, and the Arnold and
   Mabel Beckman Initiative for Macular Research supported the collection
   of UAB eyes (C.A.C., D.S.). David Fisher provided schematic drawings of
   retina in Figure 1.
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NR 60
TC 8
Z9 8
U1 0
U2 14
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD AUG 2
PY 2021
VL 11
IS 1
AR 15612
DI 10.1038/s41598-021-95122-3
PG 15
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA UA5HR
UT WOS:000685192900010
PM 34341398
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Maruyama, K
   Yoneda, K
   Sugita, S
   Yamamoto, Y
   Koike, M
   Peters, C
   Uchiyama, Y
   Nishida, K
AF Maruyama, Kazuichi
   Yoneda, Kazuhito
   Sugita, Sunao
   Yamamoto, Yoshimi
   Koike, Masato
   Peters, Christoph
   Uchiyama, Yasuo
   Nishida, Kohji
TI CTLA-2 Alpha Is a Potent Inhibitor of Angiogenesis in Murine Ocular
   Tissue
SO ANTIOXIDANTS
LA English
DT Article
DE corneal inflammation; choroidal neovascularization; cytotoxic T
   lymphocyte antigen-2 alpha; angiogenesis
AB Cytotoxic T lymphocyte antigen-2 (CTLA-2) alpha has been reported to suppress the activities of cathepsin L (Cath L), which is deeply involved in angiogenesis. Therefore, we assessed whether CTLA-2 alpha plays a role in angiogenesis in ocular tissue. To establish models of corneal inflammation and experimental choroidal neovascularization (CNV), male C57BL/6J mice (n = 5) underwent corneal suture placement or laser-induced CNV, respectively. Mice were then injected with recombinant CTLA-2 alpha (1 mu g) into the peritoneal cavity at day 0 and every 2 days after operation. In vitro experiments were performed to assess the inflammatory response by measuring TNF-alpha secretion in peritoneal cavity exudate cells (PECs) or the proliferation of mouse vascular endothelial cells (mVECs). CTLA-2 alpha treatment dramatically suppressed corneal angiogenesis, as well as laser-induced CNV. Moreover, CTLA-2 alpha inhibited the proliferation of mVECs in vitro, while CTLA-2 alpha abolishment was able to rescue proliferation. However, CTLA-2 alpha could not suppress cytokine secretion from inflammatory cells such as PECs. In summary, CTLA-2 alpha was able to suppress angiogenesis by suppressing endothelial cell proliferation. Further studies are needed to investigate its usefulness as a new antiangiogenic treatment for a variety of conditions, including age-related macular degeneration.
C1 [Maruyama, Kazuichi] Osaka Univ, Dept Vis Informat, Grad Sch Med, Suita, Osaka 5650871, Japan.
   [Maruyama, Kazuichi; Nishida, Kohji] Osaka Univ, Inst Open & Transdisciplinary Res Initiat OTRI, Integrated Frontier Res Med Sci Div, Osaka 5650871, Japan.
   [Yoneda, Kazuhito] Kyoto Prefectural Univ, Dept Ophthalmol, Grad Sch Med, Kyoto 6020841, Japan.
   [Sugita, Sunao] RIKEN, Ctr Dev Biol, Kobe, Hyogo 6500047, Japan.
   [Yamamoto, Yoshimi] Yamaguchi Univ, Dept Vet Sci, Lab Biochem & Radiat Biol, Fac Agr, Yamaguchi 7538511, Japan.
   [Koike, Masato] Juntendo Univ, Dept Cell Biol & Neurosci, Grad Sch Med, Tokyo 1138421, Japan.
   [Peters, Christoph] Univ Freiburg, Inst Mol Med & Cell Res, D-79098 Freiburg, Germany.
   [Uchiyama, Yasuo] Juntendo Univ, Dept Cellular & Mol Neuropathol, Grad Sch Med, Tokyo 1138421, Japan.
   [Nishida, Kohji] Osaka Univ, Dept Ophthalmol, Grad Sch Med, Suita, Osaka 5650871, Japan.
C3 Osaka University; Osaka University; Kyoto Prefectural University; RIKEN;
   Yamaguchi University; Juntendo University; University of Freiburg;
   Juntendo University; Osaka University
RP Maruyama, K (通讯作者)，Osaka Univ, Dept Vis Informat, Grad Sch Med, Suita, Osaka 5650871, Japan.; Maruyama, K (通讯作者)，Osaka Univ, Inst Open & Transdisciplinary Res Initiat OTRI, Integrated Frontier Res Med Sci Div, Osaka 5650871, Japan.
EM kazuichi.maruyama@ophthal.med.osaka-u.ac.jp; kazuyone@koto.kpu-m.ac.jp;
   sunao.sugita@riken.jp; yamataka@yamaguchi-u.ac.jp;
   mkoike@juntendo.ac.jp; christoph.peters@mol-med.uni-freiburg.de;
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NR 40
TC 0
Z9 0
U1 0
U2 2
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2076-3921
J9 ANTIOXIDANTS-BASEL
JI Antioxidants
PD MAR
PY 2021
VL 10
IS 3
AR 456
DI 10.3390/antiox10030456
PG 14
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 RD2CV
UT WOS:000633293900001
PM 33804126
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Kim, MH
   Kwon, SY
   Woo, SY
   Seo, WD
   Kim, DY
AF Kim, Myung Hee
   Kwon, So Yeon
   Woo, So-Yeun
   Seo, Woo Duck
   Kim, Dae Yu
TI Antioxidative Effects of Chrysoeriol via Activation of the Nrf2
   Signaling Pathway and Modulation of Mitochondrial Function
SO MOLECULES
LA English
DT Article
DE chrysoeriol; antioxidants; mitochondrial function; retinal pigment
   epithelium; age-related macular degeneration
ID QUALITY-CONTROL
AB Retinal pigment epithelium (RPE) cell dysfunction caused by excessive oxidative damage is partly involved in age-related macular degeneration, which is among the leading causes of visual impairment in elderly people. Here, we investigated the protective role of chrysoeriol against hydrogen peroxide (H2O2)-induced oxidative stress in RPE cells. The cellular viability, reactive oxygen species (ROS) generation, and mitochondrial function of retinal ARPE-19 cells were monitored under oxidative stress or pre-treatment with chrysoeriol. The expression levels of mitochondrial-related genes and associated transcription factors were assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Moreover, the protein expression of antioxidant signal molecules was characterized by Western blot analysis. Chrysoeriol significantly increased cell viability, reduced ROS generation, and increased the occurrence of antioxidant molecules in H2O2-treated ARPE-19 cells. Additionally, mitochondrial dysfunction caused by H2O2-induced oxidative stress was also considerably diminished by chrysoeriol treatment, which reduced the mitochondrial membrane potential (MMP) and upregulated mitochondrial-associated genes and proteins. Chrysoeriol also markedly enhanced key transcription factors (Nrf2) and antioxidant-associated genes (particularly HO-1 and NQO-1). Therefore, our study confirms the protective effect of chrysoeriol against H2O2-induced oxidative stress in RPE cells, thus confirming that it may prevent mitochondrial dysfunction by upregulating antioxidant-related molecules.
C1 [Kim, Myung Hee; Kim, Dae Yu] Inha Univ, Inha Res Inst Aerosp Med, Incheon 22212, South Korea.
   [Kwon, So Yeon] Inha Univ, Coll Engn, Dept Mech Engn, Incheon 22212, South Korea.
   [Woo, So-Yeun; Seo, Woo Duck] Natl Inst Crop Sci, Rural Dev Adm, Wanju Gun 55365, Jeollabuk Do, South Korea.
   [Kim, Dae Yu] Inha Univ, Coll Engn, Dept Elect Engn, Incheon 22212, South Korea.
   [Kim, Dae Yu] Inha Univ, Coll Engn, Ctr Sensor Syst, Incheon 22212, South Korea.
C3 Inha University; Inha University; Rural Development Administration
   (RDA), Republic of Korea; National Institute of Crop Science; Inha
   University; Inha University
RP Kim, DY (通讯作者)，Inha Univ, Inha Res Inst Aerosp Med, Incheon 22212, South Korea.; Kim, DY (通讯作者)，Inha Univ, Coll Engn, Dept Elect Engn, Incheon 22212, South Korea.; Kim, DY (通讯作者)，Inha Univ, Coll Engn, Ctr Sensor Syst, Incheon 22212, South Korea.
EM 318560@inha.ac.kr; 12180914@inha.edu; soyeon@korea.kr; swd2002@korea.kr;
   dyukim@inha.ac.kr
FU National Research Foundation of Korea (NRF) Ministry of Education
   [2018R1A6A1A03025523, 2020R1I1A1A01069428]; INHA UNIVERSITY; Cooperative
   Research Program for Agriculture Science and Technology Development,
   Rural Development Administration (RDA), Republic of Korea [PJ01421201]
FX This study was supported by the National Research Foundation of Korea
   (NRF) Ministry of Education through the Basic Science Research Program
   (Grants 2018R1A6A1A03025523 and 2020R1I1A1A01069428) and by the INHA
   UNIVERSITY Research Grant and Cooperative Research Program for
   Agriculture Science and Technology Development (Project No. PJ01421201)
   Rural Development Administration (RDA), Republic of Korea.
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NR 59
TC 12
Z9 12
U1 2
U2 15
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1420-3049
J9 MOLECULES
JI Molecules
PD JAN
PY 2021
VL 26
IS 2
AR 313
DI 10.3390/molecules26020313
PG 15
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA PX6KI
UT WOS:000611462700001
PM 33435366
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Hudson, N
   Celkova, L
   Hopkins, A
   Greene, C
   Storti, F
   Ozaki, E
   Fahey, E
   Theodoropoulou, S
   Kenna, PF
   Humphries, MM
   Curtis, AM
   Demmons, E
   Browne, A
   Liddie, S
   Lawrence, MS
   Grimm, C
   Cahill, MT
   Humphries, P
   Doyle, SL
   Campbell, M
AF Hudson, Natalie
   Celkova, Lucia
   Hopkins, Alan
   Greene, Chris
   Storti, Federica
   Ozaki, Ema
   Fahey, Erin
   Theodoropoulou, Sofia
   Kenna, Paul F.
   Humphries, Marian M.
   Curtis, Annie M.
   Demmons, Eleanor
   Browne, Akeem
   Liddie, Shervin
   Lawrence, Matthew S.
   Grimm, Christian
   Cahill, Mark T.
   Humphries, Pete
   Doyle, Sarah L.
   Campbell, Matthew
TI Dysregulated claudin-5 cycling in the inner retina causes retinal
   pigment epithelial cell atrophy
SO JCI INSIGHT
LA English
DT Article
ID MACULAR DEGENERATION; GENE-EXPRESSION; AGE; JUNCTIONS; PROGRESSION;
   BARRIER; CLOCK; BMAL1
AB Age-related macular degeneration (AMD) is the leading cause of central retinal vision loss worldwide, with an estimated 1 in 10 people over the age of 55 showing early signs of the condition. There are currently no forms of therapy available for the end stage of dry AMD, geographic atrophy (GA). Here, we show that the inner blood-retina barrier (iBRB) is highly dynamic and may play a contributory role in GA development. We have discovered that the gene CLDNS, which encodes claudin-5, a tight junction protein abundantly expressed at the iBRB, is regulated by BMAL1 and the circadian clock. Persistent suppression of claudin-5 expression in mice exposed to a cholesterolenriched diet induced striking retinal pigment epithelium (RPE) cell atrophy, and persistent targeted suppression of claudin-5 in the macular region of nonhuman primates induced RPE cell atrophy. Moreover, fundus fluorescein angiography in human and nonhuman primate subjects showed increased retinal vascular permeability in the evening compared with the morning. These findings implicate an inner retina-derived component in the early pathophysiological changes observed in ANC, and we suggest that restoring the integrity of the iBRB may represent a novel therapeutic target for the prevention and treatment of GA secondary to dry AMD.
C1 [Hudson, Natalie; Celkova, Lucia; Hopkins, Alan; Greene, Chris; Kenna, Paul F.; Humphries, Marian M.; Humphries, Pete; Campbell, Matthew] Trinity Coll Dublin, Smurfit Inst Genet, Lincoln Pl Gate, Dublin 2, Ireland.
   [Hopkins, Alan; Kenna, Paul F.; Cahill, Mark T.] Royal Victoria Eye & Ear Hosp, Res Fdn, Dublin, Ireland.
   [Storti, Federica; Grimm, Christian] Univ Zurich, Dept Ophthalmol, Lab Retinal Cell Biol, Zurich, Switzerland.
   [Ozaki, Ema; Fahey, Erin; Doyle, Sarah L.] Trinity Coll Dublin, Sch Med, Dublin, Ireland.
   [Theodoropoulou, Sofia] Univ Bristol, Acad Unit Ophthalmol, Sch Clin Sci, Bristol, Avon, England.
   [Curtis, Annie M.] Royal Coll Surgeons Ireland, Dept Mol & Cellular Therapeut, Dublin, Ireland.
   [Demmons, Eleanor; Browne, Akeem; Liddie, Shervin; Lawrence, Matthew S.] RxGen, Hamden, CT USA.
C3 Trinity College Dublin; University of Zurich; Trinity College Dublin;
   University of Bristol; Royal College of Surgeons - Ireland
RP Campbell, M (通讯作者)，Trinity Coll Dublin, Smurfit Inst Genet, Lincoln Pl Gate, Dublin 2, Ireland.
EM Matthew.Campbell@tcd.ie
OI Grimm, Christian/0000-0001-9318-4352; Greene, Chris/0000-0003-4192-9433;
   Hopkins, Alan/0000-0002-6497-8425; Theodoropoulou,
   Sofia/0000-0003-3038-5354; Fahey, Erin/0000-0002-8871-2090
FU Science Foundation Ireland (SFI) [12/YI/B2614, 11/PI/1080]; Health
   Research Board of Ireland; BrightFocus Foundation; Irish Research
   Council; Research Foundation at the Royal Victoria Eye and Ear Hospital;
   SFI Centres grant [16/RC/3948]; European Regional Development Fund by
   FutureNeuro industry partners; Enterprise Ireland
FX This work was supported by grants from Science Foundation Ireland (SFI)
   (12/YI/B2614 and 11/PI/1080), the Health Research Board of Ireland, the
   BrightFocus Foundation, the Irish Research Council, Enterprise Ireland,
   and The Research Foundation at the Royal Victoria Eye and Ear Hospital.
   The Campbell lab at TCD is also supported by an SFI Centres grant
   supported in part by a research grant from SFI under grant number
   16/RC/3948 and cofunded under the European Regional Development Fund by
   FutureNeuro industry partners. The authors thank Joshua Dunaief and
   Hannah Schultz for assistance with histopathology. We thank Caroline
   Woods and Charles Murray for animal husbandry.
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NR 33
TC 19
Z9 19
U1 0
U2 6
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA
EI 2379-3708
J9 JCI INSIGHT
JI JCI Insight
PD AUG 8
PY 2019
VL 4
IS 15
AR e130273
DI 10.1172/jci.insight.130273
PG 13
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA IP9YK
UT WOS:000480406700024
PM 31391341
OA Green Accepted, Green Submitted, gold, Green Published
DA 2022-11-30
ER

PT J
AU Farajipour, H
   Rahimian, S
   Taghizadeh, M
AF Farajipour, Hasan
   Rahimian, Susan
   Taghizadeh, Mohsen
TI Curcumin: A new candidate for retinal disease therapy?
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE curcumin; retina diseases; therapy
ID CIRCULATING MICRORNAS; OXIDATIVE STRESS; ENDOTHELIAL-CELLS;
   RETINOBLASTOMA PROTEIN; DIABETIC-RETINOPATHY; DIAGNOSTIC BIOMARKER;
   CANCER-DIAGNOSIS; RISK-FACTORS; CYCLIN D1; EXPRESSION
AB The retina is the neural portion and light-sensitive layer of the eye, which has been observed in most of the vertebrates. The retina is composed of light-sensitive cells that absorb light and convert it into neural signals. These signals are sent to the brain for visual recognition. It has been shown that many pathogenesis conditions, including inflammation, angiogenesis, oxidative stress, and imbalanced histone modi?cations in the retina are associated with initiation and progression of retinal diseases (ie, glaucoma, diabetic retinopathy, and age-related macular degeneration). Currently available treatments include laser surgery, freezing, stem-cell therapy, shrinking abnormal blood vessels. It has some limitations, such as invasive methods, high costs, and many side effects. Hence, finding a new therapeutic platform for stopping or slowing of the disease progression is required. Curcumin is a natural product, which is associated with a wide range of properties, such as antioxidant, anti-inflammatory, antiangiogenic, and antitumor activates. It exerts therapeutic effects via activation/inhibition cellular and molecular targets involved in various diseases, such as retinal diseases. Increasing evidence revealed that curcumin can be used as a therapeutic option in the treatment of different retinal diseases. Here, we summarized various clinical and preclinical studies that used curcumin as a therapeutic agent in the treatment of retinal disorders.
C1 [Farajipour, Hasan] Kashan Univ Med Sci, Kashan, Iran.
   [Rahimian, Susan] Kashan Univ Med Sci, Sch Dent, Oral & Maxillofacial Radiol Dept, Kashan, Iran.
   [Taghizadeh, Mohsen] Kashan Univ Med Sci, Res Ctr Biochem & Nutr Metab Dis, Kashan 8715988141, Iran.
RP Taghizadeh, M (通讯作者)，Kashan Univ Med Sci, Res Ctr Biochem & Nutr Metab Dis, Kashan 8715988141, Iran.
EM mohsenta44@yahoo.com
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NR 90
TC 13
Z9 13
U1 1
U2 23
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0730-2312
EI 1097-4644
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD MAY
PY 2019
VL 120
IS 5
BP 6886
EP 6893
DI 10.1002/jcb.28068
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA HO6VK
UT WOS:000461070700009
PM 30548307
DA 2022-11-30
ER

PT J
AU Temple, SE
   Roberts, NW
   Misson, GP
AF Temple, Shelby E.
   Roberts, Nicholas W.
   Misson, Gary P.
TI Haidinger's brushes elicited at varying degrees of polarization rapidly
   and easily assesses total macular pigmentation
SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND
   VISION
LA English
DT Article
ID HETEROCHROMATIC FLICKER PHOTOMETRY; RESONANCE RAMAN MEASUREMENT;
   AGE-RELATED MACULOPATHY; OPTICAL-DENSITY; SPATIAL-DISTRIBUTION;
   RISK-FACTORS; DEGENERATION; CAROTENOIDS; LUTEIN; AUTOFLUORESCENCE
AB Macular pigments (MPs), by absorbing potentially toxic short-wavelength (400-500 nm) visible light, provide protection against photo-chemical damage thought to be relevant in the pathogenesis of age-related macular degeneration (AMD). A method of screening for low levels of MPs could be part of a prevention strategy for helping people to delay the onset of AMD. We introduce a new method for assessing MP density that takes advantage of the polarization-dependent absorption of blue light by MPs, which results in the entoptic phenomenon called Haidinger's brushes (HB). Subjects were asked to identify the direction of rotation of HB when presented with a circular stimulus illuminated with an even intensity of polarized white light in which the electric field vector was rotating either clockwise or anti-clockwise. By reducing the degree of polarization of the stimulus light, a threshold for perceiving HB (degree of polarization threshold) was determined and correlated (r(2) = 0.66) to macular pigment optical density assessed using dual-wavelength fundus autofluoresence. The speed and ease of measurement of degree of polarization threshold makes it well suited for large-scale screening of macular pigmentation. Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License.
C1 [Temple, Shelby E.] Univ Bristol, Sch Biol Sci, Bristol BS8 1TQ, Avon, England.
   [Temple, Shelby E.; Roberts, Nicholas W.] Azul Opt Ltd, Brighton BS10 5BD, E Sussex, England.
   [Misson, Gary P.] Aston Univ, Sch Life & Hlth Sci, Birmingham B4 7ET, W Midlands, England.
   [Misson, Gary P.] South Warwickshire NHS Fdn Trust, Warwick Hosp, Lakin Rd, Warwick CV34 5BW, England.
C3 University of Bristol; Aston University
RP Temple, SE (通讯作者)，Univ Bristol, Sch Biol Sci, Bristol BS8 1TQ, Avon, England.; Temple, SE (通讯作者)，Azul Opt Ltd, Brighton BS10 5BD, E Sussex, England.
EM shelbytb@hotmail.com
RI Temple, Shelby/ABE-7207-2020
OI Temple, Shelby/0000-0001-6447-4713; Roberts,
   Nicholas/0000-0002-4540-6683; Misson, Gary/0000-0001-8843-8389
FU Innovate UK [900042]; Engineering and Physical Sciences Research Council
   (EPSRC) [EP/M000885/1]; Biotechnology and Biological Sciences Research
   Council (BBSRC); EPSRC [EP/M000885/1] Funding Source: UKRI
FX Innovate UK (900042); Engineering and Physical Sciences Research Council
   (EPSRC) (EP/M000885/1); Biotechnology and Biological Sciences Research
   Council (BBSRC) (Impact Acceleration Award).
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NR 65
TC 8
Z9 9
U1 0
U2 3
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 1084-7529
EI 1520-8532
J9 J OPT SOC AM A
JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis.
PD APR 1
PY 2019
VL 36
IS 4
BP B123
EP B131
DI 10.1364/JOSAA.36.00B123
PG 9
WC Optics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Optics
GA HR0UQ
UT WOS:000462844800019
PM 31044990
OA Green Published, Green Accepted
DA 2022-11-30
ER

PT J
AU Kamao, H
   Mild, A
   Kiryu, J
AF Kamao, Hiroyuki
   Mild, Atsushi
   Kiryu, Junichi
TI ROCK Inhibitor-Induced Promotion of Retinal Pigment Epithelial Cell
   Motility during Wound Healing
SO JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID GTP-BINDING PROTEIN; CLINICOPATHOLOGICAL CORRELATION; FUNDUS
   AUTOFLUORESCENCE; SERINE/THREONINE KINASE; TEARS; ADHESION; SECONDARY;
   THERAPY; REPAIR
AB Purpose. No standard therapy for RPE tear, a complication of neovascular age-related macular degeneration, exists even though RPE tears cause severe vision loss, and promotion of cell proliferation and/or migration could be a candidate RPE tear therapy. The aim of this study is to evaluate the effect of Rho-associated coiled-coil containing kinase (ROCK) inhibitor Y27632 on retinal pigment epithelial (RPE) cell motility during wound healing. Methods. Human RPE cells were cultured in media with and without 10M Y27632. A luminescent cell viability assay and vinculin immunocytochemistry were used to test the Y27632 effect on RPE cell adhesion. The mean size of vinculin puncta was quantified from immunofluorescence images. RPE cell motility during wound healing was evaluated using time-lapse imaging and measuring cell migration distances and cell coverage rate in wound fields. Results. The number of adhered RPE and mean size of vinculin puncta were, respectively, 20519 cells and 3.65m(2) under nontreatment and 23569cells and 0.66m(2) under Y27632 treatment. Cell migration distance and cell coverage percentage for untreated and Y27632-treated cells were 98.9 and 59.4% and 203.4 and 92.5%, respectively. Conclusions. Inhibition of ROCK signaling by using 10M Y27632 promoted RPE cell motility during wound healing by reducing RPE cell adhesion strength.
C1 [Kamao, Hiroyuki; Mild, Atsushi; Kiryu, Junichi] Kawasaki Med Sch, Dept Ophthalmol, 577 Matsushima, Kurashiki, Okayama 7010114, Japan.
C3 Kawasaki Medical School
RP Kamao, H (通讯作者)，Kawasaki Med Sch, Dept Ophthalmol, 577 Matsushima, Kurashiki, Okayama 7010114, Japan.
EM hironeri@med.kawasaki-m.ac.jp
OI Kamao, Hiroyuki/0000-0002-2194-7063
FU Sanyo Broadcasting Foundation; Alcon Japan research grant (2017); Bayer;
   Kawasaki Medical School [29Ki-7]
FX This research was supported by the Sanyo Broadcasting Foundation (2017
   to H.K.), Alcon Japan research grant (2017 to H.K.), and Bayer Academic
   Support (2018 to H.K.); Academic Contributions from Pfizer Japan Inc.
   (2018 to J.K.); and Grant-in-Aid for Scientific Research from Kawasaki
   Medical School (29Ki-7 to H.K.). We are particularly grateful to Kiyomi
   Maitani for excellent technical assistance.
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NR 43
TC 4
Z9 4
U1 0
U2 2
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 9428738
DI 10.1155/2019/9428738
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA IG2ZH
UT WOS:000473668900001
PM 31316826
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Cohen, SY
   Miere, A
   Nghiem-Buffet, S
   Fajnkuchen, F
   Souied, EH
   Mrejen, S
AF Cohen, Salomon Y.
   Miere, Alexandra
   Nghiem-Buffet, Sylvia
   Fajnkuchen, Franck
   Souied, Eric H.
   Mrejen, Sarah
TI Clinical applications of optical coherence tomography angiography: What
   we have learnt in the first 3 years
SO EUROPEAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Review
DE Optical coherence tomography; optical coherence tomography angiography;
   age-related macular degeneration; choroidal neovascularization; diabetic
   macular edema; retinal vascular occlusion; choroidal tumors; central
   serous chorioretinopathy; myopia
ID FOVEAL AVASCULAR ZONE; RETINAL VEIN OCCLUSION; POLYPOIDAL CHOROIDAL
   VASCULOPATHY; CENTRAL SEROUS CHORIORETINOPATHY; INDOCYANINE GREEN
   ANGIOGRAPHY; DIABETIC MACULAR ISCHEMIA; ACUTE MIDDLE MACULOPATHY; SOURCE
   OCT ANGIOGRAPHY; NEOVASCULARIZATION EARLY RESPONSE; PIGMENT EPITHELIAL
   DETACHMENTS
AB A review of the literature from 2014 to 2016 was conducted, focusing on the results of optical coherence tomography angiography in different chorioretinal diseases. In only 3years, optical coherence tomography angiography has been shown to be an effective tool for diagnosing choroidal neovascularization complicating age-related macular degeneration, pathologic myopia, and inflammatory conditions. The technique has sometimes been considered superior to conventional multimodal imaging, for example, in choroidal neovascularization associated with chronic central serous chorioretinopathy or multifocal choroiditis. In retinal vascular diseases, optical coherence tomography angiography has helped to understand the condition described as paracentral acute middle maculopathy and has been considered highly effective for the analysis of retinal vascular macular changes secondary to retinal vein occlusion or macular telangiectasia. Changes in the foveal avascular zone, also reported in diabetic maculopathy, have been shown to occur before any angiographic signs. A reduction in capillary vascular density has been reported in the fovea of eyes with malignant melanoma, but not in eyes with choroidal nevus. However, optical coherence tomography angiography is a recent technique that probably needs refinements and further studies. Nevertheless, the first 3 years of optical coherence tomography angiography use suggest its clinical relevance and useful applications in daily clinical practice.
C1 [Cohen, Salomon Y.; Nghiem-Buffet, Sylvia; Fajnkuchen, Franck; Mrejen, Sarah] Ophthalmol Ctr Imaging & Laser, 11 Rue Antoine Bourdelle, F-75015 Paris, France.
   [Cohen, Salomon Y.; Miere, Alexandra; Souied, Eric H.] Univ Paris Est, Dept Ophthalmol, Creteil, France.
C3 Universite Paris-Est-Creteil-Val-de-Marne (UPEC)
RP Cohen, SY (通讯作者)，Ophthalmol Ctr Imaging & Laser, 11 Rue Antoine Bourdelle, F-75015 Paris, France.
EM sycsyc75@gmail.com
RI Miere, Alexandra/AIC-4074-2022
OI Miere, Alexandra/0000-0003-4123-8210
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NR 165
TC 14
Z9 13
U1 0
U2 7
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 2018
VL 28
IS 5
BP 491
EP 502
DI 10.1177/1120672117753704
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA GU6XH
UT WOS:000445460800003
PM 29554812
DA 2022-11-30
ER

PT J
AU Mohamed, R
   Sharma, I
   Ibrahim, AS
   Saleh, H
   Elsherbiny, NM
   Fulzele, S
   Elmasry, K
   Smith, SB
   Al-Shabrawey, M
   Tawfik, A
AF Mohamed, Riyaz
   Sharma, Isha
   Ibrahim, Ahmed S.
   Saleh, Heba
   Elsherbiny, Nehal M.
   Fulzele, Sadanand
   Elmasry, Khaled
   Smith, Sylvia B.
   Al-Shabrawey, Mohamed
   Tawfik, Amany
TI Hyperhomocysteinemia Alters Retinal Endothelial Cells Barrier Function
   and Angiogenic Potential via Activation of Oxidative Stress
SO SCIENTIFIC REPORTS
LA English
DT Article
ID VASCULAR-PERMEABILITY; PLASMA HOMOCYSTEINE; HYDROGEN-SULFIDE;
   NITRIC-OXIDE; DYSFUNCTION; MICE; REPERFUSION; INHIBITION; ISCHEMIA;
   GROWTH
AB Hyperhomocysteinemia (HHcy) is associated with several human visual disorders, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Breakdown of the blood-retinal barrier (BRB) is linked to vision loss in DR and AMD. Our previous work revealed that HHcy altered BRB in retinal endothelial cells in vivo. Here we hypothesize that homocysteine (Hcy) alters retinal endothelial cell barrier function and angiogenic potential via activation of oxidative stress. Human retinal endothelial cells (HRECs) treated with and without different concentrations of Hcy showed a reduction of tight junction protein expression, increased FITC dextran leakage, decreased transcellular electrical resistance and increased angiogenic potential. In addition, HRECs treated with Hcy showed increased production of reactive oxygen species (ROS). The anti-oxidant N-acetyl-cysteine (NAC) reduced ROS formation and decreased FITC-dextran leakage in Hcy treated HRECs. A mouse model of HHcy, in which cystathionine-beta-synthase is deficient (cbs(-/-)), was evaluated for oxidative stress by dichlolorofluorescein (DCF), dihydroethidium (DHE) staining. There was a marked increase in ROS production and augmented GSH reductase and antioxidant regulator NRF2 activity, but decreased antioxidant gene expression in retinas of hyperhomocysteinemic mice. Our results suggest activation of oxidative stress as a possible mechanism of HHcy induced retinal endothelial cell dysfunction.
C1 [Mohamed, Riyaz; Sharma, Isha; Ibrahim, Ahmed S.; Saleh, Heba; Elsherbiny, Nehal M.; Elmasry, Khaled; Al-Shabrawey, Mohamed; Tawfik, Amany] Augusta Univ, Dept Oral Biol & Anat, Dent Coll Georgia, Augusta, GA 30912 USA.
   [Mohamed, Riyaz; Sharma, Isha; Ibrahim, Ahmed S.; Saleh, Heba; Elsherbiny, Nehal M.; Elmasry, Khaled; Smith, Sylvia B.; Al-Shabrawey, Mohamed; Tawfik, Amany] Augusta Univ, James & Jean Culver Vis Discovery Inst, Med Coll Georgia, Augusta, GA 30912 USA.
   [Ibrahim, Ahmed S.; Elsherbiny, Nehal M.] Mansoura Univ, Dept Biochem, Fac Pharm, Mansoura, Egypt.
   [Elmasry, Khaled; Smith, Sylvia B.; Al-Shabrawey, Mohamed; Tawfik, Amany] Augusta Univ, Dept Cellular Biol & Anat, MCG, Augusta, GA 30912 USA.
   [Smith, Sylvia B.; Al-Shabrawey, Mohamed; Tawfik, Amany] Augusta Univ, Dept Ophthalmol, MCG, Augusta, GA 30912 USA.
   [Fulzele, Sadanand] Augusta Univ, Dept Orthoped Surg, MCG, Augusta, GA USA.
C3 University System of Georgia; Augusta University; University System of
   Georgia; Augusta University; Egyptian Knowledge Bank (EKB); Mansoura
   University; University System of Georgia; Augusta University; University
   System of Georgia; Augusta University; University System of Georgia;
   Augusta University
RP Tawfik, A (通讯作者)，Augusta Univ, Dept Oral Biol & Anat, Dent Coll Georgia, Augusta, GA 30912 USA.; Tawfik, A (通讯作者)，Augusta Univ, James & Jean Culver Vis Discovery Inst, Med Coll Georgia, Augusta, GA 30912 USA.; Tawfik, A (通讯作者)，Augusta Univ, Dept Cellular Biol & Anat, MCG, Augusta, GA 30912 USA.; Tawfik, A (通讯作者)，Augusta Univ, Dept Ophthalmol, MCG, Augusta, GA 30912 USA.
EM amtawfik@augusta.edu
RI Elsherbiny, Nehal/AAF-9206-2019; Tawfik, Amany/AAN-9902-2020;
   elsherbiny, nehal N/M-5006-2018; Al-Shabrawey, Mohamed/P-9570-2018
OI Elsherbiny, Nehal/0000-0001-5167-3377; Tawfik,
   Amany/0000-0002-0245-8256; elsherbiny, nehal N/0000-0001-5167-3377;
   Sharma, isha/0000-0001-7370-5659; Mohamed, Riyaz/0000-0003-2398-3057
FU Dental College of Georgia, a pilot project grant from the James & Jean
   Culver Vision Discovery Institute (VDI); American Heart Association
   (AHA) Scientist Development Grant [16SDG30700016]; Shabrawey's
   laboratory [5R01EY023315-02]; NATIONAL EYE INSTITUTE [R01EY012830,
   R01EY023315] Funding Source: NIH RePORTER
FX This publication was made possible by startup funds from the Dental
   College of Georgia, a pilot project grant from the James & Jean Culver
   Vision Discovery Institute (VDI) and American Heart Association (AHA)
   Scientist Development Grant award #16SDG30700016. The work in Dr.
   Al-Shabrawey's laboratory is supported in part by 5R01EY023315-02. We
   also would like to thank Dr. Michael D. Pluth, (Department of Chemistry
   and Biochemistry, University of Oregon) for providing the H2S probe for
   our study and Dr. Barbara Mysona (Department of Cellular Biology and
   Anatomy, Augusta University) and Dr. Catherine Jauregui (Department of
   Oral Biology, Augusta University) for English language editing.
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NR 49
TC 30
Z9 32
U1 1
U2 5
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD SEP 20
PY 2017
VL 7
AR 11952
DI 10.1038/s41598-017-09731-y
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA FH5DV
UT WOS:000411185100005
PM 28931831
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Lu, AT
   Hannon, E
   Levine, ME
   Crimmins, EM
   Lunnon, K
   Mill, J
   Geschwind, DH
   Horvath, S
AF Lu, Ake T.
   Hannon, Eilis
   Levine, Morgan E.
   Crimmins, Eileen M.
   Lunnon, Katie
   Mill, Jonathan
   Geschwind, Daniel H.
   Horvath, Steve
TI Genetic architecture of epigenetic and neuronal ageing rates in human
   brain regions
SO NATURE COMMUNICATIONS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; ENDOTHELIN-CONVERTING ENZYME-1; DNA METHYLATION
   AGE; ALZHEIMERS-DISEASE; SUSCEPTIBILITY LOCI; PARKINSONS-DISEASE;
   COGNITIVE FUNCTION; HUMAN TISSUES; METAANALYSIS; CLOCK
AB Identifying genes regulating the pace of epigenetic ageing represents a new frontier in genome-wide association studies (GWASs). Here using 1,796 brain samples from 1,163 individuals, we carry out a GWAS of two DNA methylation-based biomarkers of brain age: the epigenetic ageing rate and estimated proportion of neurons. Locus 17q11.2 is significantly associated (P = 4.5 x 10(-9)) with the ageing rate across five brain regions and harbours a cis-expression quantitative trait locus for EFCAB5 (P = 3.4 x 10(-20)). Locus 1p36.12 is significantly associated (P = 2.2 x 10(-8)) with epigenetic ageing of the prefrontal cortex, independent of the proportion of neurons. Our GWAS of the proportion of neurons identified two genome-wide significant loci (10q26 and 12p13.31) and resulted in a gene set that overlaps significantly with sets found by GWAS of age-related macular degeneration (P = 1.4 x 10(-12)), ulcerative colitis (P < 1.0 x 10(-20)), type 2 diabetes (P = 2.8 x 10(-13)), hip/waist circumference in men (P = 1.1 x 10(-9)), schizophrenia (P = 1.6 x 10(-9)), cognitive decline (P = 5.3 x 10(-4)) and Parkinson's disease (P = 8.6 x 10(-3)).
C1 [Lu, Ake T.; Levine, Morgan E.; Geschwind, Daniel H.; Horvath, Steve] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Hannon, Eilis; Lunnon, Katie; Mill, Jonathan] Univ Exeter, Med Sch, RILD Bldg,Barrack Rd, Exeter EX2 5DW, Devon, England.
   [Levine, Morgan E.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA.
   [Crimmins, Eileen M.] Univ Southern Calif, Davis Sch Gerontol, Ethel Percy Andrus Gerontol Ctr, 3715 McClintock Ave, Los Angeles, CA 90089 USA.
   [Mill, Jonathan] Kings Coll London, Inst Psychiat, London SE5 8AF, England.
   [Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Neurogenet Program, Los Angeles, CA 90095 USA.
   [Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst, Ctr Autism Res & Treatment, Los Angeles, CA 90095 USA.
   [Horvath, Steve] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, 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 Exeter; University of California
   System; University of California Los Angeles; University of Southern
   California; University of London; King's College London; 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; University of California System;
   University of California Los Angeles
RP Horvath, S (通讯作者)，Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.; Horvath, S (通讯作者)，Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA.
EM shorvath@mednet.ucla.edu
RI Mill, Jonathan/B-5678-2014; Hannon, Eilis/T-1349-2019; Lunnon,
   Katie/C-4638-2012
OI Mill, Jonathan/0000-0003-1115-3224; Hannon, Eilis/0000-0001-6840-072X;
   Lunnon, Katie/0000-0001-7570-6065
FU Paul G. Allen Family Foundation; National Institutes of Health [NIA/NIH
   5R01AG042511-02, NIAGADS P30AG10161, R01AG15819, AG/NIA NIH R01AG17917,
   AG/NIA NIH HHS R01AG36042]; NATIONAL INSTITUTE ON AGING [P30AG010161,
   R01AG036042, U01AG009740, U34AG051425, R01AG042511, R01AG015819] Funding
   Source: NIH RePORTER
FX The study was supported by the Paul G. Allen Family Foundation and by
   the National Institutes of Health (NIA/NIH 5R01AG042511-02). The
   Religious Order Study (GWAS data sets 6 and 7) was supported by National
   Institutes of Health (NIAGADS P30AG10161, R01AG15819, AG/NIA NIH
   R01AG17917 and AG/NIA NIH HHS R01AG36042).
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NR 68
TC 57
Z9 58
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAY 18
PY 2017
VL 8
AR 15353
DI 10.1038/ncomms15353
PG 14
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA EV1MB
UT WOS:000401509300001
PM 28516910
OA Green Submitted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Montassar, F
   Darche, M
   Blaizot, A
   Augustin, S
   Conart, JB
   Millet, A
   Elayeb, M
   Sahel, JA
   Goazigo, ARL
   Sennlaub, F
   Marrakchi, N
   Messadi, E
   Guillonneau, X
AF Montassar, Fadoua
   Darche, Marie
   Blaizot, Amandine
   Augustin, Sebastien
   Conart, Jean-Baptiste
   Millet, Aurelie
   Elayeb, Mohamed
   Sahel, Jose-Alain
   Goazigo, Annabelle Reaux-Le
   Sennlaub, Florian
   Marrakchi, Naziha
   Messadi, Erij
   Guillonneau, Xavier
TI Lebecetin, a C-type lectin, inhibits choroidal and retinal
   neovascularization
SO FASEB JOURNAL
LA English
DT Article
DE integrins; snake venom; retinopathy; angiogenesis; macular degeneration
ID OXYGEN-INDUCED RETINOPATHY; INTEGRIN ALPHA-5-BETA-1; MACULAR
   DEGENERATION; MOUSE MODEL; IN-VITRO; ANGIOGENESIS; ANTAGONIST;
   ALPHA(V)BETA(3); RANIBIZUMAB; ACTIVATION
AB Angiogenesis is a cause of visual impairment and blindness in the wet form of age-related macular degeneration and in ischemic retinopathies. Current therapies include use of anti-VEGF agents to reduce choroidal neovascularization (CNV) and edema. These treatments are effective in most cases, but spontaneous or acquired resistance to anti-VEGF and possible adverse effects of long-term VEGF inhibition in the retina and choroid highlight a need for additional alternative therapies. Integrins alpha v beta 3 and alpha v beta 5, which regulate endothelial cell proliferation and stabilization, have been implicated in ocular angiogenesis. Lebecetin (LCT) is a 30-kDa heterodimeric C-type lectin that is isolated from Macrovipera lebetina venom and interacts with alpha 5 beta 1-and alpha v-containing integrins. We previously showed that LCT inhibits human brain microvascular endothelial cell adhesion, migration, proliferation, and tubulogenesis. To evaluate the inhibitory effect of LCT on ocular angiogenesis, we cultured aortic and choroidal explants in the presence of LCT and analyzed the effect of LCT on CNV in the mouse CNV model and on retinal neovascularization in the oxygen-induced retinopathy model. Our data demonstrate that a single injection of LCT efficiently reduced CNV and retinal neovascularization in these models.
C1 [Montassar, Fadoua; Darche, Marie; Blaizot, Amandine; Augustin, Sebastien; Conart, Jean-Baptiste; Sahel, Jose-Alain; Goazigo, Annabelle Reaux-Le; Sennlaub, Florian; Guillonneau, Xavier] Sorbonne Univ, Univ Pierre & Marie Curie, Ctr Natl Rech Sci, INSERM,Inst Vis, Paris, France.
   [Montassar, Fadoua; Millet, Aurelie; Elayeb, Mohamed; Marrakchi, Naziha; Messadi, Erij] Inst Pasteur Tunis, Lab Venins & Biomol Therapeut LR11IPT08, Tunis, Tunisia.
   [Montassar, Fadoua] Univ Carthage, Fac Sci Bizerte, Bizerte, Tunisia.
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; Le Reseau International des Instituts
   Pasteur (RIIP); Universite de Tunis-El-Manar; Institut Pasteur Tunis;
   Universite de Carthage
RP Guillonneau, X (通讯作者)，INSERM, Inst Vis, Unit Mixte Rech S968, 17 Rue Moreau, F-75012 Paris, France.
EM xavier.guillonneau@inserm.fr
RI Conart, Jean-Baptiste/AAD-8547-2019; Goazigo, Annabelle
   Reaux-Le/F-2753-2017; guillonneau, xavier/AAF-9495-2021; Guillonneau,
   xavier/E-3995-2017; Sennlaub, Florian/F-2756-2017; Sahel,
   Jose-Alain/F-3172-2017
OI Goazigo, Annabelle Reaux-Le/0000-0003-3855-9523; guillonneau,
   xavier/0000-0001-7379-3935; Guillonneau, xavier/0000-0001-7379-3935;
   Sennlaub, Florian/0000-0003-4412-1341; Sahel,
   Jose-Alain/0000-0002-4831-1153; Michaelides, Michel/0000-0002-1552-7046
FU INSERM; Labex Lifesenses; Partenariat Hubert Curien (PHC)-Utique Program
   (Ministere de l'Enseignement Superieur et de la Recherche Scientifique
   de Tunisie and the Ministere des Affaires Etrangeres de France);
   Institute Pasteur International Network; Carnot
FX This work was supported by grants from INSERM, Labex Lifesenses, Carnot,
   Partenariat Hubert Curien (PHC)-Utique Program (Ministere de
   l'Enseignement Superieur et de la Recherche Scientifique de Tunisie and
   the Ministere des Affaires Etrangeres de France), and the Institute
   Pasteur International Network. The authors declare no conflicts of
   interest.
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NR 55
TC 13
Z9 14
U1 0
U2 16
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 MAR
PY 2017
VL 31
IS 3
BP 1107
EP +
DI 10.1096/fj.201600351R
PG 15
WC Biochemistry & Molecular Biology; Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
   Topics; Cell Biology
GA EM9ZX
UT WOS:000395671200024
PM 27974593
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Chhetri, J
   Jacobson, G
   Gueven, N
AF Chhetri, J.
   Jacobson, G.
   Gueven, N.
TI Zebrafish-on the move towards ophthalmological research
SO EYE
LA English
DT Article
DE zebrafish; vision; visual behaviour; ocular diseases; retina; drug
   development
ID VISUAL-SYSTEM DEFECTS; DANIO-RERIO; DRUG DISCOVERY; MODEL SYSTEM;
   INTRAFLAGELLAR TRANSPORT; INTRAOCULAR-PRESSURE; OPTOKINETIC RESPONSE;
   MACULAR DEGENERATION; DIABETIC-RETINOPATHY; RETINAL DEVELOPMENT
AB Millions of people are affected by visual impairment and blindness globally, and the prevalence of vision loss is likely to increase as we are living longer. However, many ocular diseases remain poorly controlled due to lack of proper understanding of the pathogenesis and the corresponding lack of effective therapies. Consequently, there is a major need for animal models that closely mirror the human eye pathology and at the same time allow higher-throughput drug screening approaches. In this context, zebrafish as an animal model organism not only address these needs but can in many respects reflect the human situation better than the current rodent models. Over the past decade, zebrafish have become an established model to study a variety of human diseases and are more recently becoming a valuable tool for the study of human ophthalmological disorders. Many human ocular diseases such as cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration have already been modelled in zebrafish. In addition, zebrafish have become an attractive model for pre-clinical drug toxicity testing and are now increasingly used by scientists worldwide for the discovery of novel treatment approaches. This review presents the advantages and uses of zebrafish for ophthalmological research.
   Eye (2014) 28, 367-380; doi: 10.1038/eye.2014.19; published online 7 February 2014
C1 [Chhetri, J.; Jacobson, G.; Gueven, N.] Univ Tasmania, Sch Pharm, Hobart, Tas 7001, Australia.
C3 University of Tasmania
RP Gueven, N (通讯作者)，Univ Tasmania, Sch Pharm, Hobart, Tas 7001, Australia.
EM Nuri.Guven@utas.edu.au
RI Jacobson, Glenn/J-7883-2014
OI Jacobson, Glenn/0000-0002-3409-8769; Guven, Nuri/0000-0003-3782-767X
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NR 119
TC 80
Z9 81
U1 4
U2 43
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD APR
PY 2014
VL 28
IS 4
BP 367
EP 380
DI 10.1038/eye.2014.19
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AE9VT
UT WOS:000334360000001
PM 24503724
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Varma, R
   Hsu, CY
   Wang, DD
   Torres, M
   Azen, SP
AF Varma, Rohit
   Hsu, Chunyi
   Wang, Dandan
   Torres, Mina
   Azen, Stanley P.
CA Chinese Amer Eye Study Grp
TI The Chinese American Eye Study: Design and Methods
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE Chinese American; epidemiology; methodology; population-based; visual
   impairment
ID IDENTITY ACCULTURATION SCALE; CARE TECHNOLOGY FORUM; TANJONG PAGAR
   SURVEY; CLASSIFICATION-SYSTEM; CLINICAL RESEARCH; LENS OPACITIES;
   PREVALENCE; GLAUCOMA; POPULATION; SINGAPORE
AB Purpose: To summarize the study design, operational strategies and procedures of the Chinese American Eye Study (CHES), a population-based assessment of the prevalence of visual impairment, ocular disease, and visual functioning in Chinese Americans.
   Methods: This population-based, cross-sectional study included 4570 Chinese participants aged 50 years and older, residing in the city of Monterey Park, California. Each eligible participant completed a detailed interview and eye examination. The interview included an assessment of demographic, behavioral and ocular risk factors and health-related and vision-related quality of life. The eye examination included measurements of visual acuity, intraocular pressure, visual fields, fundus and optic disc photography, a detailed anterior and posterior segment examination, and measurements of blood pressure, glycosylated hemoglobin levels, and blood glucose levels.
   Results: The objectives of the CHES are to obtain prevalence estimates of visual impairment, refractive error, diabetic retinopathy, open-angle and angle-closure glaucoma, lens opacities, and age-related macular degeneration in Chinese Americans. In addition, outcomes include effect estimates for risk factors associated with eye diseases. Lastly, CHES will investigate the genetic determinants of myopia and glaucoma.
   Conclusion: The CHES will provide information about the prevalence and risk factors of ocular diseases in one of the fastest growing minority groups in the United States.
C1 [Varma, Rohit; Hsu, Chunyi; Wang, Dandan; Torres, Mina] Univ Illinois, Dept Ophthalmol & Visual Sci, Illinois Eye & Ear Infirm, Chicago, IL USA.
   [Azen, Stanley P.] Univ So Calif, Keck Sch Med, Doheny Eye Inst, Los Angeles, CA 90089 USA.
   [Azen, Stanley P.] Univ So Calif, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90089 USA.
   [Azen, Stanley P.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
C3 University of Illinois System; University of Illinois Chicago;
   University of Illinois Chicago Hospital; Doheny Eye Institute;
   University of Southern California; University of Southern California;
   University of Southern California
RP Varma, R (通讯作者)，Illinois Eye & Ear Infirm, 1855 West Taylor St,Suite 3-138 MC 648, Chicago, IL 60612 USA.
EM rvarma@uic.edu
FU National Eye Institute, National Institutes of Health, Bethesda, MD
   [EY-017337]; Research to Prevent Blindness, Inc., New York, NY; NATIONAL
   EYE INSTITUTE [U10EY017337] Funding Source: NIH RePORTER
FX This work was supported by grant EY-017337 from the National Eye
   Institute, National Institutes of Health, Bethesda, MD and by an
   unrestricted grant from Research to Prevent Blindness, Inc., New York,
   NY; Rohit Varma is a Research to Prevent Blindness Sybil B. Harrington
   Scholar.
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NR 36
TC 33
Z9 33
U1 0
U2 13
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0928-6586
EI 1744-5086
J9 OPHTHAL EPIDEMIOL
JI Ophthalmic Epidemiol.
PD DEC
PY 2013
VL 20
IS 6
BP 335
EP 347
DI 10.3109/09286586.2013.823505
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 256OC
UT WOS:000327322100002
PM 24044409
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Sakimoto, S
   Kidoya, H
   Kamei, M
   Naito, H
   Yamakawa, D
   Sakaguchi, H
   Wakabayashi, T
   Nishida, K
   Takakura, N
AF Sakimoto, Susumu
   Kidoya, Hiroyasu
   Kamei, Motohiro
   Naito, Hisamichi
   Yamakawa, Daishi
   Sakaguchi, Hirokazu
   Wakabayashi, Taku
   Nishida, Kohji
   Takakura, Nobuyuki
TI An Angiogenic Role for Adrenomedullin in Choroidal Neovascularization
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; IN-VIVO; CELLS; HYPOXIA; MICE; MACROPHAGES;
   INDUCTION; ISCHEMIA; PEPTIDE; MODEL
AB Purpose: Adrenomedullin (ADM) has been shown to take part in physiological and pathological angiogenesis. The purpose of this study was to investigate whether ADM signaling is involved in choroidal neovascularization (CNV) using a mouse model.
   Methods and Results: CNV was induced by laser photocoagulation in 8-week-old C57BL/6 mice. ADM mRNA expression significantly increased following treatment, peaking 4 days thereafter. The expression of ADM receptor (ADM-R) components (CRLR, RAMP2 and RAMP 3) was higher in CD31(+) CD45(-) endothelial cells (ECs) than CD31(-) CD45(-) non-ECs. Inflammatory stimulation upregulated the expression of ADM not only in cell lines but also in cells in primary cultures of the choroid/retinal pigment epithelium complex. Supernatants from TNF alpha-treated macrophage cell lines potentiated the proliferation of ECs and this was partially suppressed by an ADM antagonist, ADM (22-52). Intravitreous injection of ADM (22-52) or ADM neutralizing monoclonal antibody (mAb) after laser treatment significantly reduced the size of CNV compared with vehicle-treated controls (p<0.01).
   Conclusions: ADM signaling is involved in laser-induced CNV formation, because both an ADM antagonist and ADM mAb significantly inhibited it. Suppression of ADM signaling might be a valuable alternative treatment for CNV associated with age-related macular degeneration.
C1 [Sakimoto, Susumu; Kidoya, Hiroyasu; Naito, Hisamichi; Yamakawa, Daishi; Wakabayashi, Taku; Takakura, Nobuyuki] Osaka Univ, Microbial Dis Res Inst, Dept Signal Transduct, Suita, Osaka 565, Japan.
   [Sakimoto, Susumu; Kamei, Motohiro; Sakaguchi, Hirokazu; Wakabayashi, Taku; Nishida, Kohji] Osaka Univ, Grad Sch Med, Dept Ophthalmol, Suita, Osaka, Japan.
   [Takakura, Nobuyuki] JST Japan Sci & Technol Agcy, CREST, Tokyo, Japan.
C3 Osaka University; Osaka University; Japan Science & Technology Agency
   (JST)
RP Takakura, N (通讯作者)，Osaka Univ, Microbial Dis Res Inst, Dept Signal Transduct, Suita, Osaka 565, Japan.
EM ntakaku@biken.osaka-u.ac.jp
OI Naito, Hisamichi/0000-0002-0750-1743; Nishida, Kohji/0000-0001-9069-3610
FU Ministry of Education, Science, Sports, and Culture of Japan
FX This work was supported by a grant from the Ministry of Education,
   Science, Sports, and Culture of Japan. The funders had no role in study
   design, data collection and analysis, decision to publish.
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NR 39
TC 9
Z9 10
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 8
PY 2013
VL 8
IS 3
AR e58096
DI 10.1371/journal.pone.0058096
PG 8
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 140TZ
UT WOS:000318679900046
PM 23520487
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Kim, P
   Yeung, SN
   Lichtinger, A
   Amiran, MD
   Shanmugam, SV
   Iovieno, A
   Slomovic, AR
   Rootman, DS
AF Kim, Peter
   Yeung, Sonia N.
   Lichtinger, Alejandro
   Amiran, Maoz D.
   Shanmugam, Shobha V.
   Iovieno, Alfonso
   Slomovic, Allan R.
   Rootman, David S.
TI Outcomes of Repeat Endothelial Keratoplasty in Patients With Failed
   Descemet Stripping Endothelial Keratoplasty
SO CORNEA
LA English
DT Article
DE endothelial keratoplasty; Descemet stripping endothelial keratoplasty;
   DSAEK; endothelial failure
ID PENETRATING KERATOPLASTY; CELL LOSS; DMEK; EYES
AB Purpose: To report the outcomes of repeat endothelial keratoplasty (EK) in patients with failed Descemet stripping endothelial keratoplasty (DSEK).
   Methods: The clinical records of patients with failed DSEK who underwent repeat EK surgery at a single institution were reviewed.
   Results: A total of 20 eyes of 20 patients (8 men and 12 women) were included. The mean age at initial DSEK surgery was 69.9 +/- 11.9 years (range, 41-83 years). The causes of DSEK failure included progressive endothelial failure (8 eyes; 40%), primary graft failure (8 eyes; 40%), and endothelial rejection (4 eyes; 20%). The mean duration from primary DSEK to repeat EK was 13.1 +/- 10.3 months (range, 2-33 months). Removal of the failed DSEK donor disc was performed in all eyes. Mean preoperative corrected distance visual acuity (logMAR) before repeat EK surgery was 1.76, and this improved to 0.5 (P < 0.001) at the final follow-up at 27 months. Three eyes had limited corrected distance visual acuity secondary to ocular comorbidities (age-related macular degeneration and advanced glaucomatous optic neuropathy).
   Conclusions: Repeat EK in patients with DSEK failure is an effective treatment modality. This is the preferred management option compared with penetrating keratoplasty because the advantages of EK surgery are maintained with repeat EK surgery.
C1 [Kim, Peter; Yeung, Sonia N.; Lichtinger, Alejandro; Amiran, Maoz D.; Shanmugam, Shobha V.; Iovieno, Alfonso; Slomovic, Allan R.; Rootman, David S.] Univ Toronto, Toronto Western Hosp, Dept Ophthalmol, Toronto, ON M5T 2S8, Canada.
C3 University of Toronto; University Toronto Affiliates; University Health
   Network Toronto
RP Kim, P (通讯作者)，Univ Toronto, Toronto Western Hosp, Dept Ophthalmol, 399 Bathurst St,E Wing 6E 401, Toronto, ON M5T 2S8, Canada.
EM peterkim76@gmail.com
RI Yeung, Sonia/AAV-2660-2020; Iovieno, Alfonso/B-2939-2011
OI Yeung, Sonia/0000-0002-1197-8026
FU Canadian National Institute for the Blind; Schwartz Reisman Fellowship,
   Toronto, Canada
FX S. N. Yeung is supported by the E.A. Baker Fellowship Fund Grant from
   the Canadian National Institute for the Blind.; M. D. Amiran is a
   recipient of the Schwartz Reisman Fellowship, Toronto, Canada for
   2010-2011.
CR Allan BDS, 2007, CORNEA, V26, P1039, DOI 10.1097/ICO.0b013e31812f66e5
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NR 25
TC 15
Z9 15
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0277-3740
J9 CORNEA
JI Cornea
PD OCT
PY 2012
VL 31
IS 10
BP 1154
EP 1157
DI 10.1097/ICO.0b013e31823d1f03
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 004QC
UT WOS:000308695200012
PM 22677635
DA 2022-11-30
ER

PT J
AU Kutty, RK
   Nagineni, CN
   Samuel, W
   Vijayasarathy, C
   Hooks, JJ
   Redmond, TM
AF Kutty, R. Krishnan
   Nagineni, Chandrasekharam N.
   Samuel, William
   Vijayasarathy, Camasamudram
   Hooks, John J.
   Redmond, T. Michael
TI Inflammatory cytokines regulate microRNA-155 expression in human retinal
   pigment epithelial cells by activating JAK/STAT pathway
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Retinal pigment epithelium; MicroRNA-155; TNF-alpha; IL-1beta;
   IFN-gamma; JAK/STAT pathway
ID MACULAR DEGENERATION; INTERFERON-GAMMA; MIR-155; PROTEINS; RECEPTOR;
   TARGET
AB Inflammatory response of the retinal pigment epithelium plays a critical role in the pathogenesis of retinal degenerative diseases such as age-related macular degeneration. Our previous studies have shown that human retinal pigment epithelial (HRPE) cells, established from adult donor eyes, respond to inflammatory cytokines by enhancing the expression of a number of cytokines and chemokines. To investigate the role of microRNA (miRNA) in regulating this response, we performed microarray analysis of miRNA expression in HRPE cells exposed to inflammatory cytokine mix (IFN-gamma + TNE-alpha + IL-1 beta). Microarray analysis revealed similar to 11-fold increase in miR-155 expression, which was validated by real-time PCR analysis. The miR-155 expression was enhanced when the cells were treated individually with IFN-gamma. TNE-alpha or IL-1 beta, but combinations of the cytokines exaggerated the effect. The increase in miR-155 expression by the inflammatory cytokines was associated with an increase in STAT1 activation as well as an increase in protein binding to putative STAT1 binding elements present in the MIR155 gene promoter region. All these activities were effectively blocked by JAK inhibitor 1. Our results show that the inflammatory cytokines increase miR-155 expression in human retinal pigment epithelial cells by activating the JAK/STAT signaling pathway. Published by Elsevier Inc.
C1 [Kutty, R. Krishnan; Samuel, William; Redmond, T. Michael] NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
   [Nagineni, Chandrasekharam N.; Hooks, John J.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
   [Vijayasarathy, Camasamudram] Natl Inst Deafness & Other Commun Disorders, 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); National Institutes of Health (NIH) - USA; NIH National
   Institute on Deafness & Other Communication Disorders (NIDCD)
RP Kutty, RK (通讯作者)，NEI, Retinal Cell & Mol Biol Lab, NIH, Bldg 6,Room 112,6 Ctr Dr,MSC 0608, Bethesda, MD 20892 USA.
EM kuttyk@nei.nih.gov
OI Redmond, T. Michael/0000-0002-1813-5291
FU National Eye Institute, NIH; NATIONAL EYE INSTITUTE [ZIAEY000277,
   ZIAEY000444] Funding Source: NIH RePORTER
FX This study was supported by the Intramural Research Program of the
   National Eye Institute, NIH.
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NR 23
TC 93
Z9 104
U1 1
U2 18
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD NOV 12
PY 2010
VL 402
IS 2
BP 390
EP 395
DI 10.1016/j.bbrc.2010.10.042
PG 6
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 688PA
UT WOS:000284862300041
PM 20950585
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Kuno, N
   Fujii, S
AF Kuno, Noriyuki
   Fujii, Shinobu
TI Biodegradable Intraocular Therapies for Retinal Disorders Progress to
   Date
SO DRUGS & AGING
LA English
DT Review
ID STRUCTURE-PROPERTY RELATIONSHIPS; GLAUCOMA FILTRATION SURGERY; MASSIVE
   POLY(ALPHA-HYDROXY ACIDS); CILIARY NEUROTROPHIC FACTOR;
   EPITHELIUM-DERIVED FACTOR; FIBROBLAST-GROWTH-FACTOR; CHOROIDAL
   NEOVASCULARIZATION; PROLIFERATIVE VITREORETINOPATHY; SUSTAINED-RELEASE;
   MACULAR DEGENERATION
AB In general, it is difficult to achieve effective levels of drugs in the vitreous and the retina via topical and/or systemic administration. Intraocular drug delivery systems that achieve longer duration of pharmacological effect with lower administration frequency are urgently needed. Intraocular sustained drug release via implantable devices or injectable particles has been investigated for the treatment of various vitreoretinal disorders. Several non-biodegradable implants are available in clinical practice or in the late developmental phase: Vitrasert (R) (ganciclovir intravitreal implant) for cytomegalovirus retinitis, Retisert (TM) (fluocinolone acetonide intravitreal implant) for non-infectious uveitis, Iluvien (TM) (fluocinolone acetonide intravitreal implant) for diabetic macular oedema, and NT-501 (a polymer implant containing human retinal epithelial cells genetically modified to secrete ciliary neurotrophic factor) for non-neovascular (dry) age-related macular degeneration and/or retinitis pigmentosa. Many biodegradable formulations, including different shapes of rods, nail-like plugs, discs, or micro- or nanoparticles, have also been investigated, but are not available as yet device, Ozurdex (TM) (dexamethasone intravitreal implant), is approved as first-line therapy for the treatment of macular oedema following branch retinal vein occlusion or central retinal vein occlusion.
   In this article, we review the progress of major biodegradable drug delivery systems currently in clinical trials or in experimental stages for the treatment of vitreoretinal disorders.
C1 [Kuno, Noriyuki; Fujii, Shinobu] Santen Pharmaceut Co Ltd, Ctr Res & Dev, Ikoma, Nara 6300101, Japan.
C3 Santen Pharmaceutical Co Ltd
RP Kuno, N (通讯作者)，Santen Pharmaceut Co Ltd, Ctr Res & Dev, 8916-16 Takayama Cho, Ikoma, Nara 6300101, Japan.
EM noriyuki.kuno@santen.co.jp
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NR 129
TC 73
Z9 75
U1 1
U2 28
PU ADIS INT LTD
PI NORTHCOTE
PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND
SN 1170-229X
EI 1179-1969
J9 DRUG AGING
JI Drugs Aging
PY 2010
VL 27
IS 2
BP 117
EP 134
DI 10.2165/11530970-000000000-00000
PG 18
WC Geriatrics & Gerontology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology; Pharmacology & Pharmacy
GA 559ZD
UT WOS:000274870400003
PM 20104938
DA 2022-11-30
ER

PT J
AU Jarrett, SG
   Lin, HJ
   Godley, BF
   Boulton, ME
AF Jarrett, Stuart G.
   Lin, Haijiang
   Godley, Bernard F.
   Boulton, Michael E.
TI Mitochondrial DNA damage and its potential role in retinal degeneration
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
DE Retinal pigment epithelium; Age-related macular degeneration;
   Mitochondria; Base excision repair; Oxidative stress; Retinal
   degeneration
ID BASE-EXCISION-REPAIR; PIGMENT EPITHELIAL-CELLS; HEREDITARY OPTIC
   NEUROPATHY; OXIDATIVE STRESS; NUCLEAR-DNA; MACULAR DEGENERATION;
   HYDROGEN-PEROXIDE; POLYMERASE-GAMMA; RAT-BRAIN; SUPEROXIDE-DISMUTASE
AB Mitochondria are central to retinal cell function and survival. There is increasing evidence to support an association between mitochondrial dysfunction and a number of retinal pathologies including age-related macular degeneration (AMD), diabetic retinopathy and glaucoma. The past decade has highlighted mitochondrial genomic instability as an important factor in mitochondrial impairment culminating in age-related changes and age-related pathology. This represents a combination of the susceptibility of mitochondrial DNA (mtDNA) to oxidative damage and a limited base excision repair pathway. This random cumulative mtDNA damage leads to cellular heteroplasmy and, if the damage affects a sufficient proportion of mitochondria within a given cell, results in loss of cell function and greater susceptibility to stress. mtDNA damage is increased in the neural retina and RPE with ageing and appears to be greatest in AMD. It thus appears that the mitochondrial genome is a weak link in the antioxidant defenses of retinal cells and that deficits in mitochondrial DNA (mtDNA) repair pathways are important contributors to the pathogenesis of retinal degeneration. Specifically targeting mitochondria with pharmacological agents able to protect against oxidative stress or promote repair of mtDNA damage may offer potential alternatives for the treatment of retinal degenerations such as AMD. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Boulton, Michael E.] Univ Florida, Coll Med, Dept Anat & Cell Biol, Gainesville, FL 32610 USA.
   [Jarrett, Stuart G.] Univ Kentucky, Coll Med, Dept Mol & Biomed Pharmacol, Lexington, KY USA.
   [Lin, Haijiang; Godley, Bernard F.] Univ Texas Med Branch, Dept Ophthalmol & Visual Sci, Galveston, TX 77550 USA.
C3 State University System of Florida; University of Florida; University of
   Kentucky; University of Texas System; University of Texas Medical Branch
   Galveston
RP Boulton, ME (通讯作者)，Univ Florida, Coll Med, Dept Anat & Cell Biol, POB 100235, Gainesville, FL 32610 USA.
EM meboulton@ufl.edu
OI Jarrett, Stuart/0000-0001-8029-1554; Lin, Haijiang/0000-0003-2931-468X
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NR 174
TC 187
Z9 200
U1 0
U2 20
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1350-9462
EI 1873-1635
J9 PROG RETIN EYE RES
JI Prog. Retin. Eye Res.
PD NOV
PY 2008
VL 27
IS 6
BP 596
EP 607
DI 10.1016/j.preteyeres.2008.09.001
PG 12
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 382RS
UT WOS:000261623700002
PM 18848639
DA 2022-11-30
ER

PT J
AU Lahdenranta, J
   Sidman, RL
   Pasqualini, R
   Arap, W
AF Lahdenranta, Johanna
   Sidman, Richard L.
   Pasqualini, Renata
   Arap, Wadih
TI Treatment of hypoxia-induced retinopathy with targeted proapoptotic
   peptidomimetic in a mouse model of disease
SO FASEB JOURNAL
LA English
DT Article
DE aminopeptidases; angiogenesis; peptide ligand; targeted therapy
ID ENDOTHELIAL GROWTH-FACTOR; IN-VIVO; PHAGE DISPLAY; HUMAN VASCULATURE;
   AMINOPEPTIDASE-A; TUMOR; PEPTIDES; ANGIOGENESIS; DELIVERY; RECEPTOR
AB We have previously identified ligands from combinatorial peptide libraries that target tumor vasculature after in vivo selection. These ligands bind to differentially expressed receptors in angiogenic vasculature such as alpha(v)beta(3)/alpha(v)beta(5) integrins, aminopeptidase N, and aminopeptidase A. We hypothesized that we can use these ligands to target angiogenic vasculature in retinopathies. Pathological retinal angiogenesis in conditions such as diabetic retinopathy, retinopathy of prematurity, and age-related macular degeneration is a major cause of blindness for which current treatments are inadequate. Here we tested whether known tumor vasculature targeting peptide ligands displayed on bacteriophage particles would home to the proliferating blood vessels of the retina in a standard mouse model of retinopathy of prematurity. We found that activated retinal blood vessels share many of the endothelial and periendothelial cell receptors expressed in tumor vasculature. Furthermore, these vascular receptors -alpha(v) integrins and aminopeptidases -are accessible through the circulation and mediate phage homing and internalization to endothelial and periendothelial cells. Treatment of mice with a peptide containing alpha(v)beta(3)/alpha(v)beta(5) integrin targeting domain fused to a proapoptotic domain significantly reduced oxygen-induced retinal angiogenesis by selectively inducing activated endothelial cell apoptosis. Targeted proapoptotic peptides may prove useful in the management of angiogenic retinal diseases.
C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA.
   Harvard Univ, Sch Med, Boston, MA 02115 USA.
   Beth Israel Deaconess Med Ctr, Dept Neurol, Harvard Inst Med, Boston, MA 02215 USA.
C3 University of Texas System; UTMD Anderson Cancer Center; Harvard
   University; Harvard Medical School; Harvard University; Beth Israel
   Deaconess Medical Center; Harvard Medical School
RP Arap, W (通讯作者)，Univ Texas, MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM rpasqual@mdanderson.org
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NR 44
TC 25
Z9 32
U1 0
U2 6
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0892-6638
EI 1530-6860
J9 FASEB J
JI Faseb J.
PD OCT
PY 2007
VL 21
IS 12
BP 3272
EP 3278
DI 10.1096/fj.07-8273com
PG 7
WC Biochemistry & Molecular Biology; Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
   Topics; Cell Biology
GA 215BE
UT WOS:000249781600027
PM 17513561
DA 2022-11-30
ER

PT J
AU Kim, KL
   Kim, H
   Lee, Y
   Lee, C
   Joo, K
   Park, SJ
   Park, KH
   Park, SJ
   Woo, SJ
AF Kim, Kyoung Lae
   Kim, Hyerim
   Lee, Youngju
   Lee, Cheolju
   Joo, Kwangsic
   Park, Sang Jun
   Park, Kyu Hyung
   Park, Seong-Jun
   Woo, Se Joon
TI Proteomic genotyping of SNP of Complement Factor H (CFH) Y402H and I62V
   using multiple reaction monitoring (MRM) assays
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MACULAR DEGENERATION; GENE POLYMORPHISM; NO ASSOCIATION; INFLAMMATION
AB The single nucleotide polymorphisms (SNPs) of complement factor H (CFH) gene are well-known genetic risk factors for age-related macular degeneration (AMD). To identify whether the measurement of plasma protein concentrations of CFH variants using the multiple reaction monitoring (MRM) assay can determine the genotypes of CFH SNP rs1061170 and rs800292, 120 patients with AMD and 26 controls were included in this study. The number of cases were TT:TC:CC = 121:24:1 in CFH SNP Y402H and GG:AG:AA = 72:57:17 in CFH SNP I62V. Plasma concentrations of tryptic peptides were measured using the MRM assay, and tyrosine/histidine (Y/H) and valine/isoleucine (V/I) CFH variant protein ratios were obtained. To discriminate the genotypes by the plasma protein ratios, cut-off values were set for Y/H ratios (TT: > 4.428; TC: 1.00-4.428; CC: < 1.00) and V/I ratios (GG: > 1.09; AG: 0.0089-1.08; AA: < 0.0089). Correlation analysis revealed that the plasma CFH variant protein ratios and genotypes of CFH were exactly matched (100%) without overlap in the total patients and controls. The measurement of plasma protein CFH variants using the MRM assay can accurately identify the genotypes of CFH SNPs of Y402H and I62V.
C1 [Kim, Kyoung Lae; Joo, Kwangsic; Park, Sang Jun; Park, Kyu Hyung; Woo, Se Joon] Seoul Natl Univ, Coll Med, Dept Ophthalmol, Bundang Hosp, 82,Gumi Ro 173 Beon Gil, Seongnam Si 13620, Gyeonggi Do, South Korea.
   [Kim, Kyoung Lae] Hallym Univ, Kangdong Sacred Heart Hosp, Dept Ophthalmol, Coll Med, Seoul, South Korea.
   [Kim, Hyerim; Lee, Youngju; Park, Seong-Jun] RetiMark Co Ltd, Dept Res, 17 Seobinggo Ro, Seoul 04387, South Korea.
   [Lee, Cheolju] Korea Inst Sci & Technol, Ctr Theragnosis, Seoul, South Korea.
   [Park, Kyu Hyung] Seoul Natl Univ Hosp, Dept Ophthalmol, Seoul, South Korea.
C3 Seoul National University (SNU); Hallym University; Korea Institute of
   Science & Technology (KIST); Seoul National University (SNU); Seoul
   National University Hospital
RP Woo, SJ (通讯作者)，Seoul Natl Univ, Coll Med, Dept Ophthalmol, Bundang Hosp, 82,Gumi Ro 173 Beon Gil, Seongnam Si 13620, Gyeonggi Do, South Korea.; Park, SJ (通讯作者)，RetiMark Co Ltd, Dept Res, 17 Seobinggo Ro, Seoul 04387, South Korea.
EM byulmaroo@gmail.com; sejoon1@snu.ac.kr
FU National Research Foundation of Korea (NRF) - Korean government (MSIT)
   [2020R1F1A1072795, 2017M3C9A5031595, 2017M3A9F9030559]
FX This work was supported by the National Research Foundation of Korea
   (NRF) grant funded by the Korean government (MSIT) (Nos.
   2020R1F1A1072795, 2017M3C9A5031595, 2017M3A9F9030559). The funding
   organization had no role in the design or conduct of this study.
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NR 25
TC 0
Z9 0
U1 0
U2 0
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD NOV 15
PY 2022
VL 12
IS 1
AR 19587
DI 10.1038/s41598-022-20936-8
PG 9
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 6H0KC
UT WOS:000885139000024
PM 36379987
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Kaluzny, JJ
   Zabel, P
   Danek, B
   Jaworski, D
   Makowski, J
AF Kaluzny, Jakub J.
   Zabel, Przemyslaw
   Danek, Beata
   Jaworski, Damian
   Makowski, Jaroslaw
TI Intraretinal Cysts as a Manifestation of Retinal Angiomatous
   Proliferation in Optical Coherence Tomography Angiography
SO MEDICINA-LITHUANIA
LA English
DT Article
DE intraretinal cysts; retinal angiomatous proliferation; intraretinal
   neovascularization; chorioretinal anastomosis; SDOCT; OCTA
ID TYPE-3 NEOVASCULARIZATION
AB Background and Objectives: Intraretinal cysts are common pathology observed inspectral domain optical coherence tomography (SDOCT) in patients with neovascular form of age-related macular degeneration (AMD). The aim of the study was to determine if the presence of intraretinal cysts is positively correlated with diagnosis of retinal angiomatous proliferation (RAP) in optical coherence tomography angiography (OCTA). Material and Methods: A total of 21 eyes with intraretinal cysts in SDOCT exam (Group1) and 21 eyes with subretinal fluid(Group 2) were enrolled into the study. In each eye, the presence of intraretinal neovascularization (IRN) and chorioretinal anastomosis (CRA) was evaluated in OCTA by two experienced graders. Results: IRN was observed in 20 eyes (95.2%) from Group 1 and 5 eyes (23.8%) from Group 2. Features of CRA were found in 18 eyes (80.95%) and 16 eyes (76.2%) respectively for Group 1 and 2. Patients with cysts are 50 (95% CI: 5.43-460.52) times more likely to have IRN (p < 0.001). Conclusions: The presence of intraretinal cysts on SDOCT retinal sections in eyes with neovascular AMD corresponds to the presence of IRN on OCTA examination. The results indicate that the absence of a cyst does not exclude the presence of IRN and CRA which can be identified on OCTA.
C1 [Kaluzny, Jakub J.; Zabel, Przemyslaw; Danek, Beata] Nicolaus Copernicus Univ, Coll Med, Dept Sensory Organ Studies, PL-85067 Bydgoszcz, Poland.
   [Kaluzny, Jakub J.; Zabel, Przemyslaw; Danek, Beata; Jaworski, Damian; Makowski, Jaroslaw] Oftalmika Eye Hosp, PL-85631 Bydgoszcz, Poland.
   [Jaworski, Damian] Nicolaus Copernicus Univ, Coll Med, Dept Ophthalmol, Div Ophthalmol & Optometry, PL-85067 Bydgoszcz, Poland.
C3 Nicolaus Copernicus University; Nicolaus Copernicus University
RP Jaworski, D (通讯作者)，Oftalmika Eye Hosp, PL-85631 Bydgoszcz, Poland.; Jaworski, D (通讯作者)，Nicolaus Copernicus Univ, Coll Med, Dept Ophthalmol, Div Ophthalmol & Optometry, PL-85067 Bydgoszcz, Poland.
EM jjkaluzny@oftalmika.pl; przemo.zab@gmail.com; danekbeata@gmail.com;
   jaworskiresearch@gmail.com; optometrysta_jarek@wp.pl
OI Zabel, Przemyslaw/0000-0002-5219-9811; Jaworski,
   Damian/0000-0003-3842-1241
CR Amarakoon S, 2015, AM J OPHTHALMOL, V160, P1044, DOI 10.1016/j.ajo.2015.07.026
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NR 16
TC 0
Z9 0
U1 0
U2 0
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 1010-660X
EI 1648-9144
J9 MEDICINA-LITHUANIA
JI Med. Lith.
PD MAY
PY 2022
VL 58
IS 5
AR 676
DI 10.3390/medicina58050676
PG 9
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 1Q1ON
UT WOS:000802466100001
PM 35630094
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Ratra, D
   Roy, K
   Giridhar, S
   Madaan, S
AF Ratra, Dhanashree
   Roy, Krishnakanta
   Giridhar, Sneha
   Madaan, Sushant
TI Comparison Between Ranibizumab Biosimilar, Innovator Ranibizumab and
   Bevacizumab in a Real-World Situation
SO OPHTHALMOLOGY AND THERAPY
LA English
DT Article
DE Anti VEGF; Biosimilar; Comparison with bevacizumab; DME; nAMD;
   Ranibizumab
ID MACULAR DEGENERATION; AFLIBERCEPT
AB Introduction To analyze the efficacy of biosimilar ranibizumab compared to innovator ranibizumab and bevacizumab. Methods We retrospectively analyzed consecutive patients treated with biosimilar ranibizumab for wet age-related macular degeneration (AMD) and macular edema (ME) (due to diabetes and vein occlusion) and compared them with ranibizumab- and bevacizumab-treated patients. Results Of 202 patients, 67 (33.2%) received biosimilar ranibizumab (BSR), 69 (34.2%) ranibizumab (RBZ) and 66 (32.7%) bevacizumab (BEV). All patients received three consecutive injections followed by pro re nata dosing. The follow-up ranged from 3 to 24 months. The mean numbers of injections were 6.68 for RBZ, 6.4 for BEV and 4.7 for BSR. At 3 months, nAMD (n = 115, 56.9%) and ME (n = 87, 43.1%) groups showed significant improvement in vision and central foveal thickness (CFT) across all three agents. After >= 6 months, the effects were maintained in the AMD group but not in the ME group. Maximum effect was seen at 1 month. At no point in time was a significant difference noted among the three anti-vascular endothelial growth factor (anti-VEGF) agents. No major safety concerns were noted. Conclusions Biosimilar ranibizumab is comparable to innovator ranibizumab and bevacizumab in efficacy and safety.
C1 [Ratra, Dhanashree; Roy, Krishnakanta; Giridhar, Sneha; Madaan, Sushant] Sankara Nethralaya, Dept Vitreoretinal Dis, Med Res Fdn, 41-18 Coll Rd, Chennai 600006, Tamil Nadu, India.
RP Ratra, D (通讯作者)，Sankara Nethralaya, Dept Vitreoretinal Dis, Med Res Fdn, 41-18 Coll Rd, Chennai 600006, Tamil Nadu, India.
EM dhanashreeratra@gmail.com
FU Intas Pharmaceuticals Limited
FX This study was not funded by any external funding agency or source. The
   journal's Rapid Service Fee was funded by Intas Pharmaceuticals Limited.
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NR 17
TC 0
Z9 0
U1 1
U2 3
PU SPRINGER INT PUBL AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 2193-8245
EI 2193-6528
J9 OPHTHALMOL THER
JI OPHTHALMOL. THER.
PD FEB
PY 2022
VL 11
IS 1
BP 135
EP 149
DI 10.1007/s40123-021-00416-4
EA NOV 2021
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA YJ5MU
UT WOS:000714498200001
PM 34738211
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Shigemoto, Y
   Sakurada, Y
   Fukuda, Y
   Matsubara, M
   Parikh, R
   Kashiwagi, K
AF Shigemoto, Yumi
   Sakurada, Yoichi
   Fukuda, Yoshiko
   Matsubara, Mio
   Parikh, Ravi
   Kashiwagi, Kenji
TI The combination therapy of subtenon triamcinolone acetonide injection
   and intravitreal brolucizumab for brolucizumab-related intraocular
   inflammation
SO MEDICINE
LA English
DT Article
DE age related macular degeneration; brolucizumab; intraocular
   inflammation; subtenon triamcinolone acetonide
ID RANIBIZUMAB
AB Rationale: Brolucizumab is a novel anti-vascular endothelial growth factor agent with clinical trials demonstrating excellent efficacy for neovascular age-related macular degeneration (AMD) in both visual and anatomic outcomes. However, there is concern of intraocular inflammation (IOI), and we propose concurrent subtenon triamcinolone acetonide (STTA) to prevent IOI. Patient concern: A 73-year-old man was treated with aflibercept for neovascular AMD in his right eye. Despite 11 months of monthly intravitreal aflibercept injections, optical coherence tomography demonstrated persistent exudation. Ten days following his second brolucizumab injection, the patient presented with decreased vision due to vitritis in his right eye Diagnosis: Brolucizumab-related IOI in neovascular AMD refractory to aflibercept. Interventions: A combination therapy involving of intravitreal brolucizumab and STTA Outcomes: The anti-vascular endothelial growth factor inhibitor was changed back to aflibercept; however, exudation persisted. Therefore, a combination therapy involving STTA (5 mg/0.5 mL) and intravitreal injection of brolucizumab (6.0 mg/0.05 mL) was performed to treat the exudation and as prophylaxis to recurrent IOI. Combination therapy achieved no recurrent IOI and resolution of exudation with 8-week treatment intervals. Lessons: This case might indicate that STTA is not only an optimal treatment option for brolucizumab-related IOI but also a preventive agent for this condition.
C1 [Shigemoto, Yumi; Sakurada, Yoichi; Fukuda, Yoshiko; Matsubara, Mio; Kashiwagi, Kenji] Univ Yamanashi, Fac Med, Dept Ophthalmol, Kofu, Yamanashi 4093898, Japan.
   [Parikh, Ravi] Manhattan Retina & Eye Consultants, New York, NY USA.
   [Parikh, Ravi] NYU, Grossman Sch Med, New York, NY USA.
C3 University of Yamanashi; New York University
RP Sakurada, Y (通讯作者)，Univ Yamanashi, Fac Med, Dept Ophthalmol, Kofu, Yamanashi 4093898, Japan.
EM sakurada@yamanashi.ac.jp
CR Baumal CR, 2021, OPHTHALMOL RETINA, V5, P519, DOI 10.1016/j.oret.2020.09.020
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NR 17
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0025-7974
EI 1536-5964
J9 MEDICINE
JI Medicine (Baltimore)
PD OCT 22
PY 2021
VL 100
IS 42
AR e27580
DI 10.1097/MD.0000000000027580
PG 3
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA WK8VT
UT WOS:000709999400007
PM 34678906
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Sullivan, HW
   O'Donoghue, AC
   Lynch, M
   Johnson, M
   Davis, C
   Amoozegar, JB
   Rupert, DJ
AF Sullivan, Helen W.
   O'Donoghue, Amie C.
   Lynch, Molly
   Johnson, Mihaela
   Davis, Christine
   Amoozegar, Jacqueline B.
   Rupert, Douglas J.
TI Visual images of prescription drug benefits in direct-to-consumer
   television advertisements
SO PATIENT EDUCATION AND COUNSELING
LA English
DT Article
DE Prescription drug; Advertising; Television; DTCA; Quantitative
ID UNITED-STATES; NUMERACY; COMPREHENSION; INFORMATION; EXPERIENCE;
   PICTURE; RISK
AB Objective: Images demonstrating a prescription drug's efficacy are often included in direct-to-consumer television advertisements. The current research assessed whether exaggerated efficacy images can mislead individuals, and whether providing accurate quantitative information can reduce these misperceptions. Methods: We conducted two experimental studies with internet panelists 60 years and older testing drug efficacy images in television ads for wet age-related macular degeneration (N = 901) and plaque psoriasis (N = 902). In each study, participants viewed one of six ads that varied in the efficacy images included (no image, accurate image, exaggerated image) and the presentation of quantitative information (absent, present). Measures included recall, perceptions, and numeracy. Results: In both studies, participants who saw exaggerated images were more likely than those who saw no image or accurate images to overestimate efficacy. Presenting quantitative information increased participants' gist and verbatim recall of drug efficacy, and in some cases, led participants to have more accurate perceptions of the drug's efficacy even in the presence of exaggerated images. Higher numeracy was associated with better gist and verbatim recall. Conclusions: These results support visual persuasion theory. Moreover, they show that exaggerating benefits visually can mislead viewers. Practice implications: Stakeholders should ensure that images in direct-to-consumer promotion are accurate and non-misleading. Published by Elsevier B.V.
C1 [Sullivan, Helen W.; O'Donoghue, Amie C.] US FDA, Off Prescript Drug Promot, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
   [Lynch, Molly; Johnson, Mihaela; Davis, Christine; Rupert, Douglas J.] Ctr Commun Sci, RTI Int, Res Triangle Pk, NC USA.
   [Amoozegar, Jacqueline B.] Ctr Hlth Informat Res, RTI Int, Res Triangle Pk, NC USA.
C3 US Food & Drug Administration (FDA); Research Triangle Institute;
   Research Triangle Institute
RP Sullivan, HW (通讯作者)，US FDA, Off Prescript Drug Promot, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM helen.sullivan@fda.hhs.gov
OI Rupert, Douglas/0000-0001-6701-4552; Sullivan,
   Helen/0000-0001-7621-7554; Johnson, Mihaela/0000-0002-4093-7995
FU U.S. Food and Drug Administration
FX Financial support for this study was provided by a contract with the
   U.S. Food and Drug Administration. For their assistance in creating the
   study stimuli, we would like to thank David Contois and Heather Holt of
   Better World Advertising and Scott Riggan and Ari Kirschenbaum of RTI
   International. For their expertise and review, we thank Rhea Lloyd,
   Carrie Newcomer, Zarna Patel, andMeena Ramachandra of the U.S. Food and
   Drug Administration. For their help developing and refining the
   questionnaire and measurements, we thank Linda Squiers and Brian
   Southwell of RTI International.
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NR 34
TC 2
Z9 2
U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0738-3991
EI 1873-5134
J9 PATIENT EDUC COUNS
JI Patient Educ. Couns.
PD SEP
PY 2021
VL 104
IS 9
BP 2240
EP 2249
DI 10.1016/j.pec.2021.02.024
EA AUG 2021
PG 10
WC Public, Environmental & Occupational Health; Social Sciences,
   Interdisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Public, Environmental & Occupational Health; Social Sciences - Other
   Topics
GA UC7XA
UT WOS:000686735800017
PM 33618970
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Ling, CNY
   Lim, SC
   Jonas, JB
   Sabanayagam, C
AF Ng Yin Ling, Clarissa
   Lim, Su Chi
   Jonas, Jost B.
   Sabanayagam, Charumathi
TI Obesity and risk of age-related eye diseases: a systematic review of
   prospective population-based studies
SO INTERNATIONAL JOURNAL OF OBESITY
LA English
DT Review
ID BODY-MASS INDEX; LONG-TERM INCIDENCE; OPEN-ANGLE GLAUCOMA; MACULAR
   DEGENERATION; CARDIOVASCULAR-DISEASE; DIABETIC-RETINOPATHY; METABOLIC
   SYNDROME; 5-YEAR INCIDENCE; ABDOMINAL OBESITY; LENS OPACITIES
AB Background Obesity is a public health challenge worldwide. The relationship between obesity and age-related eye diseases including cataract, glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR) have remained elusive. Design and methods We conducted a systematic review of three electronic databases for longitudinal population-based studies that described associations between measures of obesity including body mass index (BMI), waist-circumference (WC), and waist-to-hip ratio (WHR), and age-related eye diseases. Results Our search yielded 1731 articles, of which 14, 10, 16 and 8 articles met our eligibility criteria for cataract, glaucoma, AMD and DR, respectively. BMI-defined obesity was positively associated with incident cataract, incident AMD and incident DR in Western populations, but in Asian populations associations for incident AMD were not significant and associations for incident DR were inverse. WC-defined obesity was associated with incident glaucoma in non-Western populations. WHR-defined obesity but not BMI-defined obesity was associated with the incidence or progression of AMD in two Western studies. Conclusions Overall, we found strong evidence supporting associations between obesity and age-related eye diseases. Further research on the association of abdominal obesity and effect of weight loss and physical activity on age-related eye diseases is warranted to support clinical and public health recommendations.
C1 [Ng Yin Ling, Clarissa] Kings Coll London, GKT Sch Med Educ, London, England.
   [Lim, Su Chi] Khoo Tech Puat Hosp, Singapore, Singapore.
   [Lim, Su Chi] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
   [Jonas, Jost B.] Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, Mannheim, Germany.
   [Sabanayagam, Charumathi] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
   [Sabanayagam, Charumathi] Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program, Singapore, Singapore.
C3 University of London; King's College London; National University of
   Singapore; Ruprecht Karls University Heidelberg; National University of
   Singapore; Singapore National Eye Center; National University of
   Singapore
RP Sabanayagam, C (通讯作者)，Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.; Sabanayagam, C (通讯作者)，Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program, Singapore, Singapore.
EM charumathi.sabanayagam@seri.com.sg
OI Sabanayagam, Charumathi/0000-0002-4042-4719; Ng Yin Ling,
   Clarissa/0000-0003-0873-5741
FU Singapore Health Services under the Medical Student Talent Development
   Award; Duke-NUS/SingHealth Academic Medicine Research Institute
FX This study was supported by funding from Singapore Health Services under
   the Medical Student Talent Development Award. The authors also
   appreciate the support of Duke-NUS/SingHealth Academic Medicine Research
   Institute. We thank Miss. Riswana Banu Binte Mohamed Abdul, Singapore
   Eye Research Institute, Singapore for her help with the formatting of
   the manuscript.
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NR 119
TC 4
Z9 4
U1 4
U2 4
PU SPRINGERNATURE
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND
SN 0307-0565
EI 1476-5497
J9 INT J OBESITY
JI Int. J. Obes.
PD SEP
PY 2021
VL 45
IS 9
BP 1863
EP 1885
DI 10.1038/s41366-021-00829-y
EA MAY 2021
PG 23
WC Endocrinology & Metabolism; Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA UE8PP
UT WOS:000649011600001
PM 33963292
DA 2022-11-30
ER

PT J
AU Wang, L
   Mao, XB
AF Wang, Liang
   Mao, Xiaobo
TI Role of Retinal Amyloid-beta in Neurodegenerative Diseases: Overlapping
   Mechanisms and Emerging Clinical Applications
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Review
DE amyloid-&#946; Alzheimer&#8217; s disease; glaucoma; age-related macular
   degeneration
AB Amyloid-beta (A beta) accumulations have been identified in the retina for neurodegeneration-associated disorders like Alzheimer's disease (AD), glaucoma, and age-related macular degeneration (AMD). Elevated retinal A beta levels were associated with progressive retinal neurodegeneration, elevated cerebral A beta accumulation, and increased disease severity with a decline in cognition and vision. Retinal A beta accumulation and its pathological effects were demonstrated to occur prior to irreversible neurodegeneration, which highlights its potential in early disease detection and intervention. Using the retina as a model of the brain, recent studies have focused on characterizing retinal A beta to determine its applicability for population-based screening of AD, which warrants a further understanding of how A beta manifests between these disorders. While current treatments directly targeting A beta accumulations have had limited results, continued exploration of A beta-associated pathological pathways may yield new therapeutic targets for preserving cognition and vision. Here, we provide a review on the role of retinal A beta manifestations in these distinct neurodegeneration-associated disorders. We also discuss the recent applications of retinal A beta for AD screening and current clinical trial outcomes for A beta-associated treatment approaches. Lastly, we explore potential future therapeutic targets based on overlapping mechanisms of pathophysiology in AD, glaucoma, and AMD.
C1 [Wang, Liang] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
   [Mao, Xiaobo] Johns Hopkins Univ, Sch Med, Neuroregenerat & Stem Cell Programs, Inst Cell Engn, Baltimore, MD 21205 USA.
   [Mao, Xiaobo] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
C3 University of Miami; Johns Hopkins University; Johns Hopkins University
RP Mao, XB (通讯作者)，Johns Hopkins Univ, Sch Med, Neuroregenerat & Stem Cell Programs, Inst Cell Engn, Baltimore, MD 21205 USA.; Mao, XB (通讯作者)，Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
EM liang.wang@med.miami.edu; xmao4@jhmi.edu
RI Mao, Xiaobo/A-7362-2010
OI Mao, Xiaobo/0000-0001-6587-556X
FU NIH [R01 NS107318, K01 AG056841]; American Parkinson's Disease
   Association; Parkinson's Foundation the Stanley Fahn Junior Faculty
   Award [PF-JFA-1933]; Maryland Stem Cell Research Foundation Discovery
   Award [2019-MSCRFD-4292]
FX This work was funded by NIH R01 NS107318, NIH K01 AG056841, American
   Parkinson's Disease Association, Parkinson's Foundation the Stanley Fahn
   Junior Faculty Award PF-JFA-1933, Maryland Stem Cell Research Foundation
   Discovery Award 2019-MSCRFD-4292.
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NR 189
TC 15
Z9 15
U1 6
U2 9
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD MAR
PY 2021
VL 22
IS 5
AR 2360
DI 10.3390/ijms22052360
PG 25
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA QV9GK
UT WOS:000628270500001
PM 33653000
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Wu, DM
   Ji, XK
   Ivanchenko, MV
   Chung, M
   Piper, M
   Rana, P
   Wang, SK
   Xue, YL
   West, E
   Zhao, SR
   Xu, HB
   Cicconet, M
   Xiong, WJ
   Cepko, CL
AF Wu, David M.
   Ji, Xuke
   Ivanchenko, Maryna, V
   Chung, Michelle
   Piper, Mary
   Rana, Parimal
   Wang, Sean K.
   Xue, Yunlu
   West, Emma
   Zhao, Sophia R.
   Xu, Hongbin
   Cicconet, Marcelo
   Xiong, Wenjun
   Cepko, Constance L.
TI Nrf2 overexpression rescues the RPE in mouse models of retinitis
   pigmentosa
SO JCI INSIGHT
LA English
DT Article
ID CONE CELL-DEATH; OXIDATIVE STRESS; RETINAL DEGENERATION; SIGNALING
   PATHWAY; ANIMAL-MODEL; R PACKAGE; GLUTATHIONE; EPITHELIUM; EXPRESSION;
   DAMAGE
AB Nrf2, a transcription factor that regulates the response to oxidative stress, has been shown to rescue cone photoreceptors and slow vision loss in mouse models of retinal degeneration (rd). The retinal pigment epithelium (RPE) is damaged in these models, but whether it also could be rescued by Nrf2 has not been previously examined. We used an adeno-associated virus (AAV) with an RPE-specific (Best1) promoter to overexpress Nrf2 in the RPE of rd mice. Control rd mice showed disruption of the regular array of the RPE, as well as loss of RPE cells. Cones were lost in circumscribed regions within the cone photoreceptor layer. Overexpression of Nrf2 specifically in the RPE was sufficient to rescue the RPE, as well as the disruptions in the cone photoreceptor layer. Electron microscopy showed compromised apical microvilli in control rd mice but showed preserved microvilli in Best1-Nrf2-treated mice. The rd mice treated with Best1-Nrf2 had slightly better visual acuity. Transcriptome profiling showed that Nrf2 upregulates multiple oxidative defense pathways, reversing declines seen in the glutathione pathway in control rd mice. In summary, Nrf2 overexpression in the RPE preserves RPE morphology and survival in rd mice, and it is a potential therapeutic for diseases involving RPE degeneration, including age-related macular degeneration (AMD).
C1 [Wu, David M.; Ji, Xuke] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Retina Serv, Boston, MA 02115 USA.
   [Wu, David M.; Ji, Xuke; Chung, Michelle; Rana, Parimal; Wang, Sean K.; Xue, Yunlu; West, Emma; Zhao, Sophia R.; Xu, Hongbin] Harvard Med Sch, Blavatnik Inst, Dept Genet, Boston, MA 02115 USA.
   [Wu, David M.; Ji, Xuke; Chung, Michelle; Rana, Parimal; Wang, Sean K.; Xue, Yunlu; West, Emma; Zhao, Sophia R.; Xu, Hongbin] Harvard Med Sch, Blavatnik Inst, Dept Ophthalmol, Boston, MA 02115 USA.
   [Ivanchenko, Maryna, V; Cepko, Constance L.] Harvard Med Sch, Dept Neurobiol, Boston, MA 02115 USA.
   [Chung, Michelle; Xu, Hongbin; Cepko, Constance L.] Howard Hughes Med Inst, Chevy Chase, MD USA.
   [Piper, Mary] TH Chan Harvard Sch Publ Hlth, Dept Bioinformat, Boston, MA USA.
   [Cicconet, Marcelo] Harvard Med Sch, Image & Data Anal Core, Boston, MA 02115 USA.
   [Xiong, Wenjun] City Univ Hong Kong, Dept Biomed Sci, Hong Kong, Peoples R China.
   [Ji, Xuke] Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA.
   [Chung, Michelle] Case Western Reserve Sch Med, Cleveland, OH USA.
   [Rana, Parimal] St Georges Med Sch, West Indies, Grenada.
C3 Harvard University; Harvard Medical School; Massachusetts Eye & Ear
   Infirmary; Harvard University; Harvard Medical School; Harvard
   University; Harvard Medical School; Harvard University; Harvard Medical
   School; Howard Hughes Medical Institute; Harvard University; Harvard
   T.H. Chan School of Public Health; Harvard University; Harvard Medical
   School; City University of Hong Kong; University of Pennsylvania; Case
   Western Reserve University
RP Cepko, CL (通讯作者)，Harvard Med Sch, HHMI, NRB Room 360,77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM cepko@genetics.med.harvard.edu
RI xu, hong/GSD-8903-2022; Xue, Yunlu/AAJ-8433-2021
OI Ivanchenko, Maryna/0000-0003-0754-1427; Wang, Sean
   K/0000-0003-1557-8510; Xue, Yunlu/0000-0002-2088-9826; Wu,
   David/0000-0001-5456-5945
FU Massachusetts Lions Eye Research Fund Inc. (DMW); HHMI; Foundation
   Fighting Blindness (SKW); Astellas Pharmaceuticals; National Institute
   on Deafness and Other Communication Disorders [R01-DC016932]; Bertarelli
   Foundation; MICRON Imaging Core at Harvard;  [NIHK08EY023993]
FX This work was funded by the NIHK08EY023993 (DMW), Massachusetts Lions
   Eye Research Fund Inc. (DMW), Iraty Award for Retina Research (DW), HHMI
   (CLC and MJC), and Foundation Fighting Blindness (SKW). CLC received
   funding from Astellas Pharmaceuticals for this work. We would like to
   thank David Corey, who assisted with the EM and is supported by National
   Institute on Deafness and Other Communication Disorders grant
   R01-DC016932 and by a gift from the Bertarelli Foundation to Harvard
   Medical School. We would also like to thank the Harvard Imaging and Data
   Analysis Core, Paola Montero and the MICRON Imaging Core at Harvard, the
   Dana Farber Molecular Biology Core Facility, Chen Wang and the Childrens
   Hospital Viral Core, and the Harvard School of Public Health
   Bioinformatics core for their contributions to this project.
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NR 80
TC 17
Z9 18
U1 0
U2 6
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA
EI 2379-3708
J9 JCI INSIGHT
JI JCI Insight
PD JAN 25
PY 2021
VL 6
IS 2
AR e145029
DI 10.1172/jci.insight.145029
PG 17
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA QA9NA
UT WOS:000613769000020
PM 33491671
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Cornebise, C
   Courtaut, F
   Taillandier-Coindard, M
   Valls-Fonayet, J
   Richard, T
   Monchaud, D
   Aires, V
   Delmas, D
AF Cornebise, Clarisse
   Courtaut, Flavie
   Taillandier-Coindard, Marie
   Valls-Fonayet, Josep
   Richard, Tristan
   Monchaud, David
   Aires, Virginie
   Delmas, Dominique
TI Red Wine Extract Inhibits VEGF Secretion and Its Signaling Pathway in
   Retinal ARPE-19 Cells to Potentially Disrupt AMD
SO MOLECULES
LA English
DT Article
DE polyphenols; red wine extract; AMD; retinal cells; ARPE-19; degenerative
   diseases; ocular diseases
ID ENDOTHELIAL GROWTH-FACTOR; PIGMENT EPITHELIAL-CELLS; MACULAR
   DEGENERATION; ANGIOGENESIS; ALCOHOL; DISEASE; HIF-1-ALPHA; EXPRESSION;
   RESISTANCE; ACID
AB Age-related macular degeneration (AMD) is a degenerative disease of the retina where the molecular mechanism involves the production of vascular endothelial growth factor (VEGF), a factor of poor prognosis of the progression of the disease. Previous studies have shown that resveratrol, a polyphenol of grapevines, can prevent VEGF secretion induced by stress from retinal cells. Considering the fundamental role played by VEGF in development and progression of AMD, we investigate the potential effect of red wine extract (RWE) on VEGF secretion and its signaling pathway in human retinal cells ARPE-19. To examine the effect of RWE in ARPE-19, a quantitative and qualitative analysis of the RWE was performed by HPLC MS/MS. We show for the first time that RWE decreased VEGF-A secretion from ARPE-19 cells and its protein expression in concentration-dependent manner. RWE-induced alteration in VEGF-A production is associated with a down of VEGF-receptor 2 (VEGF-R2) protein expression and its phosphorylated intracytoplasmic domain. Subsequently, the activation of kinase pathway is disturbing and RWE prevents the phosphorylation of MEK and ERK 1/2 in human retinal cells ARPE-19. Finally, this study sheds light on the interest that the use of polyphenolic cocktails could represent in a prevention strategy.
C1 [Cornebise, Clarisse; Courtaut, Flavie; Taillandier-Coindard, Marie; Monchaud, David; Aires, Virginie; Delmas, Dominique] Univ Bourgogne Franche Comte, F-21000 Dijon, France.
   [Cornebise, Clarisse; Courtaut, Flavie; Taillandier-Coindard, Marie; Aires, Virginie; Delmas, Dominique] INSERM, Bioact Mol & Hlth Res Grp, Res Ctr U1231, Canc & Adapt Immune Response, F-21000 Dijon, France.
   [Valls-Fonayet, Josep; Richard, Tristan] Unite Rech Oenol, EA 4577, USC 1366 INRA ISVV, F-33882 Villenave Dornon, France.
   [Monchaud, David] UBFC, Inst Chim Mol ICMUB, CNRS UMR6302, F-21078 Dijon, France.
   [Delmas, Dominique] Ctr Anticancereux Georges Francois Leclerc, F-21000 Dijon, France.
C3 Institut Agro; AgroSup Dijon; Institut National de la Sante et de la
   Recherche Medicale (Inserm); Universite de Bourgogne; INRAE;
   UDICE-French Research Universities; Universite de Bordeaux; Centre
   National de la Recherche Scientifique (CNRS); CNRS - Institute of
   Chemistry (INC); Universite de Bourgogne; UNICANCER; Centre
   Georges-Francois Leclerc
RP Delmas, D (通讯作者)，Univ Bourgogne Franche Comte, F-21000 Dijon, France.; Delmas, D (通讯作者)，INSERM, Bioact Mol & Hlth Res Grp, Res Ctr U1231, Canc & Adapt Immune Response, F-21000 Dijon, France.; Delmas, D (通讯作者)，Ctr Anticancereux Georges Francois Leclerc, F-21000 Dijon, France.
EM clarisse.cornebise@gmail.com; flavie.courtaut@gmail.com;
   marie.taillandiercoindard@gmail.com; Josep.Valls-Fonayet@U-Bordeaux.Fr;
   tristan.richard@u-bordeaux.fr; david.monchaud@u-bourgogne.fr;
   virginie.aires02@u-bourgogne.fr; dominique.delmas@u-bourgogne.fr
RI Monchaud, David/A-4492-2009
OI Monchaud, David/0000-0002-3056-9295; Delmas,
   Dominique/0000-0002-8911-8499; Richard, Tristan/0000-0002-5308-8697
FU ANRT [2016/0003]; French Government [ANR-11-LABX-0021]; Conseil Regional
   Bourgogne, Franche-Comte (PARI grant); FEDER (European Funding for
   Regional Economic Development); "Bureau Interprofessionnel des Vins de
   Bourgogne" (BIVB); Bordeaux Metabolome Facility; MetaboHUB project
   [ANR-11-INBS-0010]
FX This work was supported by grants from the ANRT Nffi2016/0003, 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, Franche-Comte (PARI
   grant) and the FEDER (European Funding for Regional Economic
   Development), the "Bureau Interprofessionnel des Vins de Bourgogne"
   (BIVB), and by the Bordeaux Metabolome Facility and MetaboHUB
   (ANR-11-INBS-0010) project.
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NR 32
TC 4
Z9 4
U1 3
U2 6
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1420-3049
J9 MOLECULES
JI Molecules
PD DEC
PY 2020
VL 25
IS 23
AR 5564
DI 10.3390/molecules25235564
PG 14
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA PD4GH
UT WOS:000597644700001
PM 33260857
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Quinn, PMJ
   Moreira, PI
   Ambrosio, AF
   Alves, CH
AF Quinn, Peter M. J.
   Moreira, Paula, I
   Ambrosio, Antonio Francisco
   Alves, C. Henrique
TI PINK1/PARKIN signalling in neurodegeneration and neuroinflammation
SO ACTA NEUROPATHOLOGICA COMMUNICATIONS
LA English
DT Review
DE PINK1; PARKIN; Mitophagy; Neurodegeneration; Alzheimer's disease;
   Parkinson's disease
ID PARKIN-MEDIATED MITOPHAGY; ALPHA-SYNUCLEIN; MITOCHONDRIAL DYSFUNCTION;
   ALZHEIMERS-DISEASE; RAT MODEL; PINK1-DEPENDENT PHOSPHORYLATION; DOPAMINE
   NEUROTRANSMISSION; DAMAGED MITOCHONDRIA; HUNTINGTONS-DISEASE;
   S-NITROSYLATION
AB Mutations in the PTEN-induced kinase 1 (PINK1) and Parkin RBR E3 ubiquitin-protein ligase (PARKIN) genes are associated with familial forms of Parkinson's disease (PD). PINK1, a protein kinase, and PARKIN, an E3 ubiquitin ligase, control the specific elimination of dysfunctional or superfluous mitochondria, thus fine-tuning mitochondrial network and preserving energy metabolism. PINK1 regulates PARKIN translocation in impaired mitochondria and drives their removal via selective autophagy, a process known as mitophagy. As knowledge obtained using different PINK1 and PARKIN transgenic animal models is being gathered, growing evidence supports the contribution of mitophagy impairment to several human pathologies, including PD and Alzheimer's diseases (AD). Therefore, therapeutic interventions aiming to modulate PINK1/PARKIN signalling might have the potential to treat these diseases. In this review, we will start by discussing how the interplay of PINK1 and PARKIN signalling helps mediate mitochondrial physiology. We will continue by debating the role of mitochondrial dysfunction in disorders such as amyotrophic lateral sclerosis, Alzheimer's, Huntington's and Parkinson's diseases, as well as eye diseases such as age-related macular degeneration and glaucoma, and the causative factors leading to PINK1/PARKIN-mediated neurodegeneration and neuroinflammation. Finally, we will discuss PINK1/PARKIN gene augmentation possibilities with a particular focus on AD, PD and glaucoma.
C1 [Quinn, Peter M. J.] Columbia Univ, Vagelos Coll Phys & Surg, Jonas Childrens Vis Care & Bernard & Shirlee Brow, Inst Human Nutr,Columbia Stem Cell Initiat,Dept O, New York, NY USA.
   [Quinn, Peter M. J.] Columbia Univ, Vagelos Coll Phys & Surg, Inst Human Nutr, Dept Pathol, New York, NY USA.
   [Quinn, Peter M. J.] Columbia Univ, Vagelos Coll Phys & Surg, Inst Human Nutr, Dept Cell Biol, New York, NY USA.
   [Quinn, Peter M. J.] New York Presbyterian Hosp, Edward S Harkness Eye Inst, New York, NY USA.
   [Moreira, Paula, I] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, Coimbra, Portugal.
   [Moreira, Paula, I; Ambrosio, Antonio Francisco; Alves, C. Henrique] Univ Coimbra, Ctr Innovat Biomed & Biotechnol CIBB, Coimbra, Portugal.
   [Moreira, Paula, I] Univ Coimbra, Fac Med, Lab Physiol, Coimbra, Portugal.
   [Ambrosio, Antonio Francisco; Alves, C. Henrique] Univ Coimbra, Fac Med, Coimbra Inst Clin & Biomed Res iCBR, Coimbra, Portugal.
   [Ambrosio, Antonio Francisco; Alves, C. Henrique] Assoc Innovat & Biomed Res Light & Image AIBILI, Coimbra, Portugal.
   [Ambrosio, Antonio Francisco; Alves, C. Henrique] Clin Acad Ctr Coimbra CACC, Coimbra, Portugal.
C3 Columbia University; Columbia University; Columbia University;
   NewYork-Presbyterian Hospital; Universidade de Coimbra; Universidade de
   Coimbra; Universidade de Coimbra; Universidade de Coimbra; Universidade
   de Coimbra; Universidade de Coimbra
RP Alves, CH (通讯作者)，Univ Coimbra, Ctr Innovat Biomed & Biotechnol CIBB, Coimbra, Portugal.; Alves, CH (通讯作者)，Univ Coimbra, Fac Med, Coimbra Inst Clin & Biomed Res iCBR, Coimbra, Portugal.; Alves, CH (通讯作者)，Assoc Innovat & Biomed Res Light & Image AIBILI, Coimbra, Portugal.; Alves, CH (通讯作者)，Clin Acad Ctr Coimbra CACC, Coimbra, Portugal.
EM chalves@fmed.uc.pt
RI Alves, Henrique/AAH-3017-2019; Moreira, Paula/B-3608-2009; Quinn, Peter
   M.J./AAF-7201-2019
OI Alves, Henrique/0000-0001-9776-5701; Moreira, Paula/0000-0001-5177-6747;
   Quinn, Peter M.J./0000-0001-9940-4264; Ambrosio, Antonio
   F/0000-0002-0477-1641
FU Foundation for Science and Technology (FCT), Portugal [UIDB/04539/2020,
   UIDP/04539/2020, CEECIND/00886/2017]; Curing Retinal Blindness
   Foundation (CRBF); Knights Templar Eye Foundation (KTEF)
FX Foundation for Science and Technology (FCT), Portugal [Strategic
   Projects: UIDB/04539/2020 and UIDP/04539/2020 (Center for Innovative
   Biomedicine and Biotechnology) to AFA; and CEECIND/00886/2017 to CHA].
   PMJQ is funded by the Curing Retinal Blindness Foundation (CRBF) and the
   Knights Templar Eye Foundation (KTEF). Foundation for Science and
   Technology (FCT), Portugal [Strategic Projects: UIDB/04539/2020 and
   UIDP/04539/2020 (Center for Innovative Biomedicine and Biotechnology) to
   AFA; and CEECIND/00886/2017 to CHA]. The funding bodies had no role in
   writing the manuscript.
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NR 215
TC 80
Z9 85
U1 16
U2 36
PU BMC
PI LONDON
PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2051-5960
J9 ACTA NEUROPATHOL COM
JI Acta Neuropathol. Commun.
PD NOV 9
PY 2020
VL 8
IS 1
AR 189
DI 10.1186/s40478-020-01062-w
PG 20
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA OT3AS
UT WOS:000590723000006
PM 33168089
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Kiel, C
   Berber, P
   Karlstetter, M
   Aslanidis, A
   Strunz, T
   Langmann, T
   Grassmann, F
   Weber, BHF
AF Kiel, Christina
   Berber, Patricia
   Karlstetter, Marcus
   Aslanidis, Alexander
   Strunz, Tobias
   Langmann, Thomas
   Grassmann, Felix
   Weber, Bernhard H. F.
TI A Circulating MicroRNA Profile in a Laser-Induced Mouse Model of
   Choroidal Neovascularization
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE cmiRNA regulation; age-related macular degeneration; laser-induced
   choroidal neovascularization; biomarker
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL-PIGMENT EPITHELIUM; MACULAR
   DEGENERATION; POTENTIAL BIOMARKERS; NATURAL-HISTORY; IN-VITRO;
   EXPRESSION; CELLS; ANGIOGENESIS; GENETICS
AB Choroidal neovascularization (CNV) is a pathological process in which aberrant blood vessels invade the subretinal space of the mammalian eye. It is a characteristic feature of the prevalent neovascular age-related macular degeneration (nAMD). Circulating microRNAs (cmiRNAs) are regarded as potentially valuable biomarkers for various age-related diseases, including nAMD. Here, we investigated cmiRNA expression in an established laser-induced CNV mouse model. Upon CNV induction in C57Bl/6 mice, blood-derived cmiRNAs were initially determined globally by RNA next generation sequencing, and the most strongly dysregulated cmiRNAs were independently replicated by quantitative reverse transcription PCR (RT-qPCR) in blood, retinal, and retinal pigment epithelium (RPE)/choroidal tissue. Our findings suggest that two miRNAs, mmu-mir-486a-5p and mmur-mir-92a-3p, are consistently dysregulated during CNV formation. Furthermore, in functional in vitro assays, a significant impact of mmu-mir-486a-5p and mmu-mir-92a-3p on murine microglial cell viability was observed, while mmu-mir-92a-3p also showed an impact on microglial mobility. Taken together, we report a robust dysregulation of two miRNAs in blood and RPE/choroid after laser-induced initiation of CNV lesions in mice, highlighting their potential role in pathology and eventual therapy of CNV-associated complications.
C1 [Kiel, Christina; Berber, Patricia; Strunz, Tobias; Grassmann, Felix; Weber, Bernhard H. F.] Univ Regensburg, Inst Human Genet, D-93053 Regensburg, Germany.
   [Karlstetter, Marcus; Aslanidis, Alexander; Langmann, Thomas] Fac Med, Dept Ophthalmol, Lab Expt Immunol Eye, D-50931 Cologne, Germany.
   [Karlstetter, Marcus; Aslanidis, Alexander; Langmann, Thomas] Univ Hosp Cologne, D-50931 Cologne, Germany.
   [Grassmann, Felix] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
   [Weber, Bernhard H. F.] Univ Clin Regensburg, Inst Clin Human Genet, D-93053 Regensburg, Germany.
C3 University of Regensburg; University of Cologne; University of Cologne;
   Karolinska Institutet; University of Regensburg
RP Weber, BHF (通讯作者)，Univ Regensburg, Inst Human Genet, D-93053 Regensburg, Germany.; Weber, BHF (通讯作者)，Univ Clin Regensburg, Inst Clin Human Genet, D-93053 Regensburg, Germany.
EM Christina.Kiel@klinik.uni-regensburg.de;
   Patricia.Berber@klinik.uni-regensburg.de; marcus.karlstetter@gmail.com;
   Alexander.Aslanidis@janvier-labs.com;
   Tobias.Strunz@klinik.uni-regensburg.de; Thomas.Langmann@uk-koeln.de;
   Felix.Grassmann@ki.se; bweb@klinik.uni-regensburg.de
RI Strunz, Tobias/ABB-6300-2020; Strunz, Tobias/ABD-9798-2021
OI Strunz, Tobias/0000-0002-3744-9595; Grassmann,
   Felix/0000-0003-1390-7528; Weber, Bernhard H.F./0000-0002-8808-7723;
   Kiel, Christina/0000-0003-3154-4847
FU Deutsche Forschungsgemeinschaft [GR5065/1-1]
FX This research was funded by the Deutsche Forschungsgemeinschaft
   (GR5065/1-1).
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NR 75
TC 7
Z9 7
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 APR
PY 2020
VL 21
IS 8
AR 2689
DI 10.3390/ijms21082689
PG 18
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA LR3AC
UT WOS:000535565300031
PM 32294914
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Yiu, G
   Chung, SH
   Mollhoff, IN
   Wang, YW
   Nguyen, UT
   Shibata, B
   Cunefare, D
   Farsiu, S
   Roberts, J
   Thomasy, SM
AF Yiu, Glenn
   Chung, Sook Hyun
   Mollhoff, Iris Natalie
   Wang, Yinwen
   Uyen Tu Nguyen
   Shibata, Bradley
   Cunefare, David
   Farsiu, Sina
   Roberts, Jeffrey
   Thomasy, Sara M.
TI Long-term Evolution and Remodeling of Soft Drusen in Rhesus Macaques
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE drusen; macular degeneration; retina; rhesus macaques; optical coherence
   tomography
ID OPTICAL COHERENCE TOMOGRAPHY; ONSET MACULAR DEGENERATION;
   RETINAL-PIGMENT EPITHELIUM; CHOROIDAL THICKNESS MEASUREMENTS;
   AGE-RELATED MACULOPATHY; GEOGRAPHIC ATROPHY; AUTOMATIC SEGMENTATION;
   REFRACTILE DRUSEN; NATURAL-HISTORY; BRUCHS MEMBRANE
AB PURPOSE. To characterize the evolution and structure of soft drusen in aged rhesus macaques using in vivo multimodal retinal imaging and ex vivo histologic and ultrastructural analyses as a nonhuman primate model of early age-related macular degeneration (AMD).
   METHODS. Multimodal imaging including fundus photography, spectral domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) were used to characterize and track individual drusen lesions in 20 aged rhesus macaques (mean age 23.3 +/- 2.7 years) with drusenoid lesions over 2 years, followed by semithin histologic analysis and transmission electron microscopy (TEM).
   RESULTS. Although most drusen gradually increased in size, a portion spontaneously regressed or collapsed over 2 years. Histologic analyses showed that soft drusen exhibit hypertrophy and dysmorphia of overlying retinal pigment epithelium (RPE), as seen in early and intermediate AMD, but do not exhibit RPE atrophy, RPE migration, or photoreceptor degeneration characteristic of advanced AMD. Ultrastructure of soft drusen showed abundant lipid particles within Bruch's membrane and AMD-related basal linear deposits (BlinD) resembling those in human drusen.
   CONCLUSIONS. The dynamic remodeling, histologic findings, and ultrastructural features of soft drusen in aged rhesus macaques support nonhuman primates as an animal model of early AMD and reveal important insights into drusen biogenesis and AMD development.
C1 [Yiu, Glenn; Chung, Sook Hyun; Mollhoff, Iris Natalie; Wang, Yinwen; Uyen Tu Nguyen; Shibata, Bradley; Thomasy, Sara M.] Univ Calif Davis, Dept Ophthalmol & Vis Sci, 4860 Y St,Suite 2400, Sacramento, CA 95817 USA.
   [Cunefare, David; Farsiu, Sina] Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA.
   [Roberts, Jeffrey] Calif Natl Primate Res Ctr, Davis, CA USA.
   [Thomasy, Sara M.] Univ Calif Davis, Sch Vet Med, Dept Surg & Radiol Sci, Davis, CA 95616 USA.
C3 University of California System; University of California Davis; Duke
   University; University of California System; University of California
   Davis
RP Yiu, G (通讯作者)，Univ Calif Davis, Dept Ophthalmol & Vis Sci, 4860 Y St,Suite 2400, Sacramento, CA 95817 USA.
EM gyiu@ucdavis.edu
FU California National Primate Research Center [NIH P510D011107]; NIA Set
   Aside program; NIH [K08 EY026101, R21 EY031108, P30 EY005722, K08
   EY021142, U24 U24EY029904, P30 EY012576]; E. Matilda Ziegler Foundation
   for the Blind; Barr Foundation for Retinal Research; ARVO Foundation;
   Macula Society
FX Supported by the California National Primate Research Center pilot grant
   program and base grant NIH P510D011107. A portion of the aged rhesus
   studied is supported by the NIA Set Aside program. Supported by NIH K08
   EY026101, NIH R21 EY031108, the E. Matilda Ziegler Foundation for the
   Blind, Barr Foundation for Retinal Research, ARVO Foundation, and Macula
   Society (GY). Supported by NIH P30 EY005722 (SF). Supported by NIH K08
   EY021142 and U24 U24EY029904 (ST). Histologic and ultrastructural
   studies were conducted at the Center for Vision Sciences
   structure-function core facility, which is supported by NIH P30
   EY012576. No funding organizations had any role in the design or conduct
   of this research. The content is solely the responsibility of the
   authors and does not necessarily represent the official views of the
   funding agencies.
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NR 82
TC 13
Z9 13
U1 1
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD FEB
PY 2020
VL 61
IS 2
AR 32
DI 10.1167/iovs.61.2.32
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA KR6TJ
UT WOS:000517748100032
PM 32084273
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Nakano, Y
   Kataoka, K
   Takeuchi, J
   Fujita, A
   Kaneko, H
   Shimizu, H
   Ito, Y
   Terasaki, H
AF Nakano, Yuyako
   Kataoka, Keiko
   Takeuchi, Jun
   Fujita, Ai
   Kaneko, Hiroki
   Shimizu, Hideyuki
   Ito, Yasuki
   Terasaki, Hiroko
TI Vascular maturity of type 1 and type 2 choroidal neovascularization
   evaluated by optical coherence tomography angiography
SO PLOS ONE
LA English
DT Article
ID MACULAR DEGENERATION; RANIBIZUMAB; MECHANISMS; THERAPY
AB Purpose
   Vessel maturation is considered to proceed by pruning branches resulting in less branching vessels. This study investigated the vessel junction densities of type 1 and type 2 choroidal neovascularizations (CNVs) using optical coherence tomography angiography (OCTA).
   Methods
   We collected consecutive data from treatment-naive eyes diagnosed with typical age-related macular degeneration (AMD). The OCTA images with CNV were analyzed to calculate vessel areas, vessel lengths, and vessel junction densities.
   Results
   Of 60 eyes in 60 patients, type 1 CNV diagnoses had been made in 40 eyes, and type 2 CNV in 20 eyes. We found no significant difference in vessel areas between type 1 CNV and type 2 CNV (type 1 CNV, 0.44 +/- 0.37 mm 2; type 2 CNV, 0.37 +/- 0.48 mm(2)), and no significant difference in vessel lengths (type 1 CNV, 18.24 +/- 15.96 mm; type 2 CNV, 16.13 +/- 21.45 mm). However, the vessel junction density of type 1 CNV was significantly lower than that of type 2 CNV by 16.0% (P = 0.008).
   Conclusion
   OCTA revealed that the vessel junction densities of type 1 CNVs were lower than those of type 2 CNVs, suggesting type 1 CNV vessels are more mature than type 2 CNV vessels.
C1 [Nakano, Yuyako; Kataoka, Keiko; Takeuchi, Jun; Fujita, Ai; Kaneko, Hiroki; Shimizu, Hideyuki; Ito, Yasuki; Terasaki, Hiroko] Nagoya Univ, Grad Sch Med, Dept Ophthalmol, Nagoya, Aichi, Japan.
C3 Nagoya University
RP Kataoka, K (通讯作者)，Nagoya Univ, Grad Sch Med, Dept Ophthalmol, Nagoya, Aichi, Japan.
EM kkeiko@med.nagoya-u.ac.jp
RI Kaneko, Hiroki/O-7695-2015; Kaneko, Hiroki/AHA-2461-2022; Ito,
   Yasuki/M-4876-2014; Kataoka, Keiko/B-2806-2016
OI Kaneko, Hiroki/0000-0003-0731-6465; Kaneko, Hiroki/0000-0003-0731-6465;
   Ito, Yasuki/0000-0001-9219-9261; Kataoka, Keiko/0000-0002-8795-6536
FU Japan Society for the Promotion of Science KAKENHI [16K20313, 16K11265]
FX This work was supported by the Japan Society for the Promotion of
   Science KAKENHI, grant numbers 16K20313 (KK) and 16K11265 (YI). The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
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NR 28
TC 15
Z9 15
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 29
PY 2019
VL 14
IS 4
AR e0216304
DI 10.1371/journal.pone.0216304
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA HV6ZL
UT WOS:000466131200054
PM 31034505
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Piippo, N
   Korhonen, E
   Hytti, M
   Skottman, H
   Kinnunen, K
   Josifovska, N
   Petrovski, G
   Kaarniranta, K
   Kauppinen, A
AF Piippo, Niina
   Korhonen, Eveliina
   Hytti, Maria
   Skottman, Heli
   Kinnunen, Kati
   Josifovska, Natasha
   Petrovski, Goran
   Kaarniranta, Kai
   Kauppinen, Anu
TI Hsp90 inhibition as a means to inhibit activation of the NLRP3
   inflammasome
SO SCIENTIFIC REPORTS
LA English
DT Article
ID PIGMENT EPITHELIAL-CELLS; ENDOTOXIN-INDUCED UVEITIS; ADVANCED SOLID
   TUMORS; I DOSE-ESCALATION; MACULAR DEGENERATION; MOLECULAR-MECHANISMS;
   ARPE-19 CELLS; GELDANAMYCIN; PREVENTION; EXPRESSION
AB Once activated, the intracellular receptor NLRP3 assembles an inflammasome protein complex that facilitates the caspase-1-mediated maturation of IL-1 beta and IL-18. Inactive NLRP3 is guarded by a protein complex containing Hsp90. In response to stress stimuli, Hsp90 is released, and NLRP3 can be activated to promote inflammation. In this study, we blocked Hsp90 with geldanamycin and studied the fate of NLRP3 in human retinal pigment epithelial (RPE) cells. RPE cells play a central role in the development of age-related macular degeneration (AMD), a progressive eye disease causing severe vision loss in the elderly. IL-1 alpha-primed ARPE-19 cells, human embryonal stem cell (hESC)-derived RPE cells, and primary human RPE cells were exposed to MG-132 and bafilomycin A to activate NLRP3 via the inhibition of proteasomes and autophagy, respectively. Additionally, RPE cells were treated with geldanamycin at different time points and the levels of NLRP3 and IL-1 beta were determined. Caspase-1 activity was measured using a commercial assay. Geldanamycin prevented the activation of the inflammasome in human RPE cells. NLRP3 released from its protective complex became degraded by autophagy or secreted from the cells. Controlled destruction of NLRP3 is a potential way to regulate the inflammation associated with chronic diseases, such as AMD.
C1 [Piippo, Niina; Korhonen, Eveliina; Hytti, Maria; Kauppinen, Anu] Univ Eastern Finland, Sch Pharm, Kuopio 70211, Finland.
   [Skottman, Heli] Univ Tampere, Fac Med & Life Sci, BioMediTech, Tampere 33014, Finland.
   [Kinnunen, Kati; Kaarniranta, Kai] Kuopio Univ Hosp, Dept Ophthalmol, Kuopio 70211, Finland.
   [Josifovska, Natasha; Petrovski, Goran] Univ Szeged, Dept Ophthalmol, Albert Szent Gyorgyi Clin Ctr, Stem Cells & Eye Res Lab,Fac Med, Szeged, Hungary.
   [Petrovski, Goran] Univ Oslo, Oslo Univ Hosp, Dept Ophthalmol, Ctr Eye Res, Oslo, Norway.
   [Kaarniranta, Kai] Univ Eastern Finland, Inst Clin Med, Dept Ophthalmol, Kuopio 70211, Finland.
C3 University of Eastern Finland; Tampere University; Kuopio University
   Hospital; University of Eastern Finland; Szeged University; University
   of Oslo; University of Eastern Finland
RP Kauppinen, A (通讯作者)，Univ Eastern Finland, Sch Pharm, Kuopio 70211, Finland.
EM anu.kauppinen@uef.fi
RI Hytti, Maria/AAE-4016-2019
OI Hytti, Maria/0000-0003-2150-6847; Korhonen,
   Eveliina/0000-0002-5360-7258; Skottman, Heli/0000-0002-4127-8792;
   Petrovski, Goran/0000-0003-2905-9252; Josifovska,
   Natasha/0000-0002-3898-9729
FU Paivikki ja Sakari Sohlberg Foundation; Finnish Eye Foundation; Finnish
   Cultural Foundation (Central and North-Savo Regional Fund); Orion-Farmos
   Research Foundation; Alfred Kordelin Foundation; Emil Aaltonen
   Foundation; Kuopio University Hospital (VTR); Academy of Finland (Health
   Research Council) [AK297267, AK307341, KK5503743, HS218050]; EU [GINOP-
   2.3.2-15-2016-00006]; European Regional Development Fund
FX We warmly acknowledge Dr. Ewen MacDonald for the language revision, and
   Res. Dir. Emeritus Antero Salminen for his valuable collaboration,
   discussions, and critical review of the manuscript. Outi Heikkila, Outi
   Melin, and Hanna Pekkanen are thanked for the technical assistance with
   hESC-RPE. This study was financially supported by Paivikki ja Sakari
   Sohlberg Foundation (AK, HS), Finnish Eye Foundation, Finnish Cultural
   Foundation (Central and North-Savo Regional Fund), Orion-Farmos Research
   Foundation, the Alfred Kordelin Foundation, Emil Aaltonen Foundation,
   Kuopio University Hospital (VTR funding), the Academy of Finland (Health
   Research Council projects AK297267, AK307341, KK5503743, and HS218050),
   and GINOP- 2.3.2-15-2016-00006 (Hungary), co-financed by the EU and the
   European Regional Development Fund.
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NR 55
TC 43
Z9 45
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD APR 30
PY 2018
VL 8
AR 6720
DI 10.1038/s41598-018-25123-2
PG 9
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA GE3HR
UT WOS:000431104900021
PM 29712950
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Cascella, R
   Strafella, C
   Longo, G
   Manzo, L
   Ragazzo, M
   De Felici, C
   Gambardella, S
   Marsella, LT
   Novelli, G
   Borgiani, P
   Sangiuolo, F
   Cusumano, A
   Ricci, F
   Giardina, E
AF Cascella, R.
   Strafella, C.
   Longo, G.
   Manzo, L.
   Ragazzo, M.
   De Felici, C.
   Gambardella, S.
   Marsella, L. T.
   Novelli, G.
   Borgiani, P.
   Sangiuolo, F.
   Cusumano, A.
   Ricci, F.
   Giardina, E.
TI Assessing individual risk for AMD with genetic counseling, family
   history, and genetic testing
SO EYE
LA English
DT Article
ID MACULAR DEGENERATION; ARMS2; CFH
AB Purpose The goal was to develop a simple model for predicting the individual risk profile for age-related macular degeneration (AMD) on the basis of genetic information, disease family history, and smoking habits.
   Patients and methods The study enrolled 151 AMD patients following specific clinical and environmental inclusion criteria: age 455 years, positive family history for AMD, presence of at least one first-degree relative affected by AMD, and smoking habits. All of the samples were genotyped for rs1061170 (CFH) and rs10490924 (ARMS2) with a TaqMan assay, using a 7500 Fast Real Time PCR device. Statistical analysis was subsequently employed to calculate the real individual risk (OR) based on the genetic data (ORgn), family history (ORf), and smoking habits (ORsm).
   Results and conclusion The combination of ORgn, ORf, and ORsm allowed the calculation of the Ort that represented the realistic individual risk for developing AMD. In this report, we present a computational model for the estimation of the individual risk for AMD. Moreover, we show that the average distribution of risk alleles in the general population and the knowledge of parents' genotype can be decisive to assess the real disease risk. In this contest, genetic counseling is crucial to provide the patients with an understanding of their individual risk and the availability for preventive actions.
C1 [Cascella, R.; Giardina, E.] Santa Lucia Fdn, UILDM, Mol Genet Lab, Via Ardeatina 354, I-00142 Rome, Italy.
   [Cascella, R.] Catholic Univ Our Lady Good Counsel, Dept Chem Pharmaceut & Biomol Technol, Rruga Dritan Hoxha, Tirane, Albania.
   [Strafella, C.; Longo, G.; Manzo, L.; Ragazzo, M.; Marsella, L. T.; Novelli, G.; Borgiani, P.; Sangiuolo, F.; Giardina, E.] Tor Vergata Univ, Dept Biomed & Prevent, Rome, Italy.
   [Strafella, C.] Emotest Lab, Pozzuoli, Italy.
   [Ragazzo, M.] Catholic Univ Our Lady Good Counsel Laprake, Dept Med Sci, Rruga Dritan Hoxha, Tirane, Albania.
   [De Felici, C.; Cusumano, A.; Ricci, F.] UOSD Retinal Pathol PTV Fdn Policlin Tor Vergata, Rome, Italy.
   [Gambardella, S.] Neuromed IRCCS, Pozzuoli, Italy.
C3 Consiglio Nazionale delle Ricerche (CNR); Istituto di Genetica
   Molecolare (IGM-CNR); IRCCS Santa Lucia; University of Rome Tor Vergata;
   IRCCS Neuromed
RP Cascella, R (通讯作者)，Santa Lucia Fdn, UILDM, Mol Genet Lab, Via Ardeatina 354, I-00142 Rome, Italy.
EM raffaellacascella@virgilio.it
RI Novelli, Giuseppe/A-5195-2013; Novelli, Giuseppe/GQB-3329-2022; ricci,
   federico/AAC-3836-2020; Manzo, Laura/AHE-6262-2022; Strafella,
   Claudia/AAA-5929-2019; Novelli, Giuseppe/T-8822-2019; Cascella,
   Raffaella/G-9040-2019; Gambardella, Stefano/AAN-5212-2020; Gambardella,
   Stefano/K-4514-2016
OI Novelli, Giuseppe/0000-0002-7781-602X; Novelli,
   Giuseppe/0000-0002-7781-602X; ricci, federico/0000-0002-4224-9280;
   Strafella, Claudia/0000-0003-1334-0920; Cascella,
   Raffaella/0000-0002-2148-0758; Gambardella, Stefano/0000-0002-3727-4502
FU Macula Foundation Onlus
FX We acknowledge the Macula Foundation Onlus that supported this work.
CR Amin N, 2009, EUR J EPIDEMIOL, V24, P585, DOI 10.1007/s10654-009-9387-y
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NR 14
TC 12
Z9 12
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 FEB
PY 2018
VL 32
IS 2
BP 446
EP 450
DI 10.1038/eye.2017.192
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA FV5VK
UT WOS:000424650300041
PM 28912512
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Jaadane, I
   Rodriguez, GEV
   Boulenguez, P
   Chahory, S
   Carre, S
   Savoldelli, M
   Jonet, L
   Behar-Cohen, F
   Martinsons, C
   Torriglia, A
AF Jaadane, Imene
   Rodriguez, Gloria Elisa Villalpando
   Boulenguez, Pierre
   Chahory, Sabine
   Carre, Samuel
   Savoldelli, Michele
   Jonet, Laurent
   Behar-Cohen, Francine
   Martinsons, Christophe
   Torriglia, Alicia
TI Effects of white light-emitting diode (LED) exposure on retinal pigment
   epithelium in vivo
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Article
DE light-emitting diode; retinal pigment epithelium degeneration; necrosis;
   oxidative stress; blue light blood-retinal barrier
ID PROTEIN-KINASE-C; LEUKOCYTE-ELASTASE-INHIBITOR; L-DNASE-II; MACULAR
   DEGENERATION; CELL-DEATH; ENDOPLASMIC-RETICULUM; OXIDATIVE STRESS;
   BLUE-LIGHT; PHOTOOXIDATIVE DAMAGE; TIGHT JUNCTIONS
AB Ageing and alteration of the functions of the retinal pigment epithelium (RPE) are at the origin of lost of vision seen in age-related macular degeneration (AMD). The RPE is known to be vulnerable to high-energy blue light. The white light-emitting diodes (LED) commercially available have relatively high content of blue light, a feature that suggest that they could be deleterious for this retinal cell layer. The aim of our study was to investigate the effects of "white LED" exposure on RPE. For this, commercially available white LEDs were used for exposure experiments on Wistar rats. Immunohistochemical stain on RPE flat mount, transmission electron microscopy and Western blot were used to exam the RPE. LED-induced RPE damage was evaluated by studying oxidative stress, stress response pathways and cell death pathways as well as the integrity of the outer blood-retinal barrier (BRB). We show that white LED light caused structural alterations leading to the disruption of the outer blood-retinal barrier. We observed an increase in oxidized molecules, disturbance of basal autophagy and cell death by necrosis. We conclude that white LEDs induced strong damages in rat RPE characterized by the breakdown of the BRB and the induction of necrotic cell death.
C1 [Jaadane, Imene; Rodriguez, Gloria Elisa Villalpando; Savoldelli, Michele; Jonet, Laurent; Behar-Cohen, Francine; Torriglia, Alicia] Univ Paris 06, Univ Paris Descartes, INSERM, U1138,Ctr Rech Cordeliers, Paris, France.
   [Jaadane, Imene; Chahory, Sabine] ENVA, Unite Ophtalmol, Maisons Alfort, France.
   [Boulenguez, Pierre; Carre, Samuel; Martinsons, Christophe] CSTB, Div Eclairage & Electromagnetisme, St Martin Dheres, France.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm);
   UDICE-French Research Universities; Sorbonne Universite; Universite
   Paris Cite; Ecole Nationale Veterinaire d'Alfort (ENVA)
RP Torriglia, A (通讯作者)，Univ Paris 06, Univ Paris Descartes, INSERM, U1138,Ctr Rech Cordeliers, Paris, France.
EM alicia.torriglia@inserm.fr
RI Torriglia, Alicia/Q-3509-2019; Torriglia, Alicia/L-6957-2017
OI Torriglia, Alicia/0000-0003-1181-6710; Martinsons,
   Christophe/0000-0002-2286-5991; Imene, Jaadane/0000-0003-1887-1659;
   Chahory, Sabine/0000-0003-2045-5515
FU INSERM (Institut national de la sante et de la recherche medicale); ENVA
   (Ecole Nationale Veterinaire d'Alfort); CSTB (Centre Scientifique et
   Technique du Batiment); ADEME (Agence de l'environnement et de la
   maitrise de l'energie) grant (RETI-NALED project); ADEME (Agence de
   l'environnement et de la maitrise de l'energie) grant (UV-LED project);
   ADEME
FX Authors are in debt with Dr. Patricia Lassiaz for helpful discussions on
   BRB and with Christophe Klein, Jade Delahaye, Cathy Claramonte and Julia
   Pardo for technical assistance. This work was supported by INSERM
   (Institut national de la sante et de la recherche medicale), ENVA (Ecole
   Nationale Veterinaire d'Alfort), CSTB (Centre Scientifique et Technique
   du Batiment) and by an ADEME (Agence de l'environnement et de la
   maitrise de l'energie) grant (RETI-NALED and UV-LED projects). IJ has a
   fellowship from ADEME.
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NR 71
TC 48
Z9 49
U1 0
U2 20
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
EI 1582-4934
J9 J CELL MOL MED
JI J. Cell. Mol. Med.
PD DEC
PY 2017
VL 21
IS 12
BP 3453
EP 3466
DI 10.1111/jcmm.13255
PG 14
WC Cell Biology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine
GA FQ7WP
UT WOS:000418574500029
PM 28661040
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Kampik, D
   Basche, M
   Luhmann, UFO
   Nishiguchi, KM
   Williams, JAE
   Greenwood, J
   Moss, SE
   Han, H
   Azam, S
   Duran, Y
   Robbie, SJ
   Bainbridge, JWB
   Larkin, DF
   Smith, AJ
   Ali, RR
AF Kampik, D.
   Basche, M.
   Luhmann, U. F. O.
   Nishiguchi, K. M.
   Williams, J. A. E.
   Greenwood, J.
   Moss, S. E.
   Han, H.
   Azam, S.
   Duran, Y.
   Robbie, S. J.
   Bainbridge, J. W. B.
   Larkin, D. F.
   Smith, A. J.
   Ali, R. R.
TI In situ regeneration of retinal pigment epithelium by gene transfer of
   E2F2: a potential strategy for treatment of macular degenerations
SO GENE THERAPY
LA English
DT Article
ID AGE-RELATED MACULOPATHY; BEAVER DAM EYE; LENTIVIRAL VECTOR;
   CELL-DENSITY; AGING RETINA; PROLIFERATION; TRANSPLANTATION;
   TRANSLOCATION; DETACHMENT; GROWTH
AB The retinal pigment epithelium (RPE) interacts closely with photoreceptors to maintain visual function. In degenerative diseases such as Stargardt disease and age-related macular degeneration, the leading cause of blindness in the developed world, RPE cell loss is followed by photoreceptor cell death. RPE cells can proliferate under certain conditions, suggesting an intrinsic regenerative potential, but so far this has not been utilised therapeutically. Here, we used E2F2 to induce RPE cell replication and thereby regeneration. In both young and old (2 and 18 month) wildtype mice, subretinal injection of non-integrating lentiviral vector expressing E2F2 resulted in 47% of examined RPE cells becoming BrdU positive. E2F2 induced an increase in RPE cell density of 17% compared with control vector-treated and 14% compared with untreated eyes. We also tested this approach in an inducible transgenic mouse model of RPE loss, generated through activation of diphtheria toxin-A gene. E2F2 expression resulted in a 10-fold increase in BrdU uptake and a 34% increase in central RPE cell density. Although in mice this localised rescue is insufficiently large to be demonstrable by electroretinography, a measure of massed retinal function, these results provide proof-of-concept for a strategy to induce in situ regeneration of RPE for the treatment of RPE degeneration.
C1 [Kampik, D.; Basche, M.; Luhmann, U. F. O.; Nishiguchi, K. M.; Azam, S.; Duran, Y.; Robbie, S. J.; Bainbridge, J. W. B.; Smith, A. J.; Ali, R. R.] UCL, Inst Ophthalmol, Dept Genet, 11-43 Bath St, London EC1V 9EL, England.
   [Kampik, D.; Han, H.] Univ Hosp Wurzburg, Dept Ophthalmol, Wurzburg, Germany.
   [Luhmann, U. F. O.] Roche Pharmaceut Res & Early Dev Ophthalmol Disco, Basel, Switzerland.
   [Nishiguchi, K. M.] Tohoku Univ, Grad Sch Med, Dept Adv Ophthalm Med, Sendai, Miyagi, Japan.
   [Williams, J. A. E.; Greenwood, J.; Moss, S. E.] UCL, Inst Ophthalmol, Dept Cell Biol, London, England.
   [Bainbridge, J. W. B.; Larkin, D. F.] Moorfields Eye Hosp, London, England.
   [Ali, R. R.] Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr, London, England.
   [Ali, R. R.] UCL, Inst Ophthalmol, London, England.
C3 University of London; University College London; University of Wurzburg;
   Tohoku University; University of London; University College London;
   University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; University of London; University College London;
   Moorfields Eye Hospital NHS Foundation Trust; University of London;
   University College London
RP Ali, RR (通讯作者)，UCL, Inst Ophthalmol, Dept Genet, 11-43 Bath St, London EC1V 9EL, England.
EM r.ali@ucl.ac.uk
RI Kampik, Daniel/AAE-9819-2020
OI Kampik, Daniel/0000-0002-8613-5875; Greenwood, John/0000-0003-4496-2984;
   Bainbridge, James/0000-0003-1318-8201; Luhmann, Ulrich
   F.O./0000-0002-1993-1951; Ali, Robin/0000-0003-3126-6517; Larkin,
   Daniel/0000-0003-2506-0280
FU National Institute for Health Research Biomedical Research Centre at
   Moorfields Eye Hospital; UCL; Moorfields Eye Charity; RP Fighting
   Blindness; National Institute for Health Research [NF-SI-0508-10130,
   NIHR-RP-011-003, NF-SI-0513-10074] Funding Source: researchfish
FX This work was supported by the National Institute for Health Research
   Biomedical Research Centre at Moorfields Eye Hospital and UCL, and also
   by Moorfields Eye Charity and RP Fighting Blindness. The authors
   gratefully acknowledge Anselm Kampik, Augenzentrum im Brienner Hof,
   Munich, Germany, for helpful discussions. The authors thank Nancy Joyce,
   Schepens Eye Research Institute, Harvard Medical School, Boston, USA,
   for providing the human E2F2 cDNA plasmid.
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NR 44
TC 11
Z9 11
U1 0
U2 2
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 DEC
PY 2017
VL 24
IS 12
BP 810
EP 818
DI 10.1038/gt.2017.89
PG 9
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 FR0ZM
UT WOS:000418794600007
PM 29188796
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Ranard, KM
   Jeon, S
   Mohn, ES
   Griffiths, JC
   Johnson, EJ
   Erdman, JW
AF Ranard, Katherine M.
   Jeon, Sookyoung
   Mohn, Emily S.
   Griffiths, James C.
   Johnson, Elizabeth J.
   Erdman, John W., Jr.
TI Dietary guidance for lutein: consideration for intake recommendations is
   scientifically supported
SO EUROPEAN JOURNAL OF NUTRITION
LA English
DT Article
DE Lutein; Intake recommendations; Bioactives; Visual performance; Macular
   degeneration
ID PIGMENT OPTICAL-DENSITY; MACULAR DEGENERATION; ZEAXANTHIN INTAKE; SERUM
   LUTEIN; EYE DISEASE; VITAMIN-E; CAROTENOIDS; AGE; RISK; BIOAVAILABILITY
AB Lutein, a yellow xanthophyll carotenoid found in egg yolks and many colorful fruits and vegetables, has gained public health interest for its putative role in visual performance and reducing the risk of age-related macular degeneration. The National Academies of Sciences, Engineering and Medicine's recommended Dietary Reference Intakes (DRIs) focus on preventing deficiency and toxicity, but there is a budding interest in establishing DRI-like guidelines for non-essential bioactives, like lutein, that promote optimal health and/or prevent chronic diseases. Lupton et al. developed a set of nine criteria to determine whether a bioactive is ready to be considered for DRI-like recommendations. These criteria include: (1) an accepted definition; (2) a reliable analysis method; (3) a food database with known amounts of the bioactive; (4) cohort studies; (5) clinical trials on metabolic processes; (6) clinical trials for dose-response and efficacy; (7) safety data; (8) systematic reviews and/or meta-analyses; (9) a plausible biological rationale. Based on a review of the literature supporting these criteria, lutein is ready to be considered for intake recommendations. Establishing dietary guidance for lutein would encourage the consumption of lutein-containing foods and raise public awareness about its potential health benefits.
C1 [Ranard, Katherine M.; Jeon, Sookyoung; Erdman, John W., Jr.] Univ Illinois, Div Nutr Sci, Urbana, IL 61801 USA.
   [Mohn, Emily S.; Johnson, Elizabeth J.] Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Boston, MA 02111 USA.
   [Griffiths, James C.] Council Responsible Nutr Int, Sci & Int Affairs, Washington, DC USA.
   [Erdman, John W., Jr.] Univ Illinois, Dept Food Sci & Human Nutr, 455 Bevier Hall,905 S Goodwin Ave, Urbana, IL 61801 USA.
C3 University of Illinois System; University of Illinois Urbana-Champaign;
   Tufts University; United States Department of Agriculture (USDA);
   University of Illinois System; University of Illinois Urbana-Champaign
RP Erdman, JW (通讯作者)，Univ Illinois, Div Nutr Sci, Urbana, IL 61801 USA.; Erdman, JW (通讯作者)，Univ Illinois, Dept Food Sci & Human Nutr, 455 Bevier Hall,905 S Goodwin Ave, Urbana, IL 61801 USA.
EM jwerdman@illinois.edu
RI Jeon, Sookyoung/AAL-8526-2021
OI Jeon, Sookyoung/0000-0002-3620-0851
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NR 46
TC 61
Z9 61
U1 2
U2 19
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1436-6207
EI 1436-6215
J9 EUR J NUTR
JI Eur. J. Nutr.
PD DEC
PY 2017
VL 56
SU 3
BP 537
EP 542
DI 10.1007/s00394-017-1580-2
PG 6
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA FX0KO
UT WOS:000425732800001
PM 29149368
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Ryoo, NK
   Lee, J
   Lee, H
   Hong, HK
   Kim, H
   Lee, JB
   Woo, SJ
   Park, KH
   Kim, H
AF Ryoo, Na-Kyung
   Lee, Jihwang
   Lee, Hyunjoo
   Hong, Hye Kyoung
   Kim, Hyejin
   Lee, Jong Bum
   Woo, Se Joon
   Park, Kyu Hyung
   Kim, Hyuncheol
TI Therapeutic effects of a novel siRNA-based anti-VEGF (siVEGF) nanoball
   for the treatment of choroidal neovascularization
SO NANOSCALE
LA English
DT Article
ID MACULAR DEGENERATION; IN-VIVO; OCULAR NEOVASCULARIZATION; CELLULAR
   UPTAKE; GENE-THERAPY; DNA DELIVERY; RETINA; NANOPARTICLES; EXPRESSION;
   MOUSE
AB Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries and is characterized by the development of choroidal neovascularization (CNV). Therapies for AMD have focused on suppressing angiogenic factors, such as vascular endothelial growth factor (VEGF), mainly via conventional anti-VEGF antibody agents. However, additional efforts have been made to develop effective small-interfering RNA (siRNA)-based intracellular therapeutic agents. In this study, we have manufactured a novel siRNA-based anti-VEGF nanoball (siVEGF NB). The siVEGF NB was composed of a siRNA hydrogel with a core of anti-VEGF sequence siRNA coated with branched PEI (bPEI) and hyaluronic acid (HA) in order by applying an electrical force. The novel siVEGF NBs, which were employed in a laser-induced CNV mouse model, were optimized as a retinal and choroidal delivery system through the vitreous humor to the sub-retinal space via CD44 receptor endocytosis on the inner limiting membrane, and showed therapeutic effects via pathways bypassing the TLR3-induced siRNA-class effect. The therapeutic effects of siVEGF NBs lasted for 2 weeks after intravitreal injection showing high targeting efficiency to the sub-retinal space. Thus, the newly developed siVEGF NB may have great potential for the delivery of RNAi-based therapeutics for ocular diseases, including AMD.
C1 [Ryoo, Na-Kyung; Hong, Hye Kyoung; Woo, Se Joon; Park, Kyu Hyung] Seoul Natl Univ, Dept Ophthalmol, Bundang Hosp, Seongnam, South Korea.
   [Ryoo, Na-Kyung; Woo, Se Joon; Park, Kyu Hyung] Seoul Natl Univ, Dept Ophthalmol, Coll Med, Seoul, South Korea.
   [Lee, Jihwang; Lee, Hyunjoo; Kim, Hyuncheol] Sogang Univ, Dept Chem & Biomol Engn, Seoul, South Korea.
   [Kim, Hyejin; Lee, Jong Bum] Univ Seoul, Dept Chem Engn, Seoul, South Korea.
C3 Seoul National University (SNU); Seoul National University (SNU); Sogang
   University; University of Seoul
RP Park, KH (通讯作者)，Seoul Natl Univ, Dept Ophthalmol, Bundang Hosp, Seongnam, South Korea.; Park, KH (通讯作者)，Seoul Natl Univ, Dept Ophthalmol, Coll Med, Seoul, South Korea.; Kim, H (通讯作者)，Sogang Univ, Dept Chem & Biomol Engn, Seoul, South Korea.
EM jiani4@snu.ac.kr; hyuncheol@sogang.ac.kr
RI Kim, Hyejin/K-8782-2018; Woo, Se Joon/I-7357-2013
OI Kim, Hyejin/0000-0002-7937-2733; Woo, Se Joon/0000-0003-3692-7169; Park,
   Kyu Hyung/0000-0002-5516-8121; kim, hyuncheol/0000-0002-7591-3053; Ryoo,
   Na-Kyung/0000-0001-5475-9774
FU Basic Science Research Program through the National Research Foundation
   of Korea (NRF) - Ministry of Education, Science and Technology
   [NRF-2013R1A2A2A04015829, NRF-2016R1A6A-1A03012845,
   NRF-2017R1A2B2003194]
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, Science and Technology (NRF-2013R1A2A2A04015829,
   NRF-2016R1A6A-1A03012845, and NRF-2017R1A2B2003194).
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NR 40
TC 25
Z9 27
U1 4
U2 82
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
   ENGLAND
SN 2040-3364
EI 2040-3372
J9 NANOSCALE
JI Nanoscale
PD OCT 28
PY 2017
VL 9
IS 40
BP 15461
EP 15469
DI 10.1039/c7nr03142d
PG 9
WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials
   Science, Multidisciplinary; Physics, Applied
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry; Science & Technology - Other Topics; Materials Science;
   Physics
GA FL0MJ
UT WOS:000413905200026
PM 28976519
DA 2022-11-30
ER

PT J
AU Cammalleri, M
   Dal Monte, M
   Locri, F
   Lardner, E
   Kvanta, A
   Rusciano, D
   Andre, H
   Bagnoli, P
AF Cammalleri, Maurizio
   Dal Monte, Massimo
   Locri, Filippo
   Lardner, Emma
   Kvanta, Anders
   Rusciano, Dario
   Andre, Helder
   Bagnoli, Paola
TI Efficacy of a Fatty Acids Dietary Supplement in a Polyethylene
   Glycol-Induced Mouse Model of Retinal Degeneration
SO NUTRIENTS
LA English
DT Article
DE complement system; inflammation; macrophage infiltration; dry
   age-related macular degeneration; dietary supplementation
ID MEMBRANE-ATTACK-COMPLEX; MACULAR DEGENERATION; PIVOTAL ROLE;
   GLIAL-CELLS; TNF-ALPHA; OMEGA-3-FATTY-ACIDS; EXPRESSION;
   NEOVASCULARIZATION; PATHOGENESIS; ACTIVATION
AB Current knowledge of the benefits of nutrition supplements for eye pathologies is based largely on the use of appropriate animal models, together with defined dietary supplementation. Here, C57BL6 mice were subretinally injected with polyethylene glycol (PEG)-400, an established model of retinal degeneration with a dry age-related macular degeneration (AMD)-like phenotype, an eye pathology that lacks treatment. In response to PEG-400, markers of the complement system, angiogenesis, inflammation, gliosis, and macrophage infiltration were upregulated in both retinas and retinal pigment epithelium (RPE)/choroids, whereas dietary supplementation with a mixture based on fatty acids counteracted their upregulation. Major effects include a reduction of inflammation, in both retinas and RPE/choroids, and an inhibition of macrophage infiltration in the choroid, yet not in the retina, suggesting a targeted action through the choroidal vasculature. Histological analysis revealed a thinning of the outer nuclear layer (ONL), together with dysregulation of the epithelium layer in response to PEG-400. In addition, immunohistofluorescence demonstrated Muller cell gliosis and macrophage infiltration into subretinal tissues supporting the molecular findings. Reduced ONL thickness, gliosis, and macrophage infiltration were counteracted by the diet supplement. The present data suggest that fatty acids may represent a useful form of diet supplementation to prevent or limit the progression of dry AMD.
C1 [Cammalleri, Maurizio; Dal Monte, Massimo; Locri, Filippo; Bagnoli, Paola] Univ Pisa, Dept Biol, Via San Zeno 31, I-56127 Pisa, Italy.
   [Cammalleri, Maurizio; Dal Monte, Massimo] Univ Pisa, Interdept Res Ctr Nutrafood Nutraceut & Food Hlth, Via Borghetto 80, I-56124 Pisa, Italy.
   [Locri, Filippo; Lardner, Emma; Kvanta, Anders; Andre, Helder] St Erik Hosp, Dept Clin Neurosci, Sect Eye & Vis, Karolinska Inst, Polhemsgatan 50, SE-11282 Stockholm, Sweden.
   [Rusciano, Dario] Sooft Fidia Pharma, Contrada Molino 17, I-63833 Montegiorgio, FM, Italy.
C3 University of Pisa; University of Pisa; Karolinska Institutet
RP Dal Monte, M; Bagnoli, P (通讯作者)，Univ Pisa, Dept Biol, Via San Zeno 31, I-56127 Pisa, Italy.; Dal Monte, M (通讯作者)，Univ Pisa, Interdept Res Ctr Nutrafood Nutraceut & Food Hlth, Via Borghetto 80, I-56124 Pisa, Italy.
EM maurizio.cammalleri@unipi.it; massimo.dalmonte@unipi.it;
   filippo.locri1@gmail.com; emma.lardner@sll.se; anders.kvanta@ki.se;
   dario.rusciano@sooft.it; helder.andre@ki.se; paola.bagnoli@unipi.it
RI Rusciano, Dario/AAP-7450-2020; Andre, Helder/AAC-5220-2019; Dal Monte,
   Massimo/AAA-9275-2022
OI Rusciano, Dario/0000-0002-9577-2585; Andre, Helder/0000-0002-2926-2376;
   CAMMALLERI, MAURIZIO/0000-0001-8934-5838
FU Sooft Fidia Pharma; Italian Ministry of Health [RF-201102351158];
   Karolinska Institute foundation; Cronqvist foundation
FX This work was supported by a grant from Sooft Fidia Pharma to M.C., by a
   grant from the Italian Ministry of Health (RF-201102351158) to P.B., and
   by grants from the Karolinska Institute foundation and the Cronqvist
   foundation to H.A. The authors wish to thank Angelo Gazzano and Gino
   Bertolini for assistance with the mouse colonies.
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NR 56
TC 8
Z9 8
U1 0
U2 2
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 2072-6643
J9 NUTRIENTS
JI Nutrients
PD OCT
PY 2017
VL 9
IS 10
AR 1079
DI 10.3390/nu9101079
PG 18
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA FM0DM
UT WOS:000414629900035
PM 28961167
OA Green Published, Green Submitted, gold
DA 2022-11-30
ER

PT J
AU Yang, XW
   Chen, H
   Zhu, MH
   Zhu, RR
   Qin, B
   Fang, HD
   Dai, M
   Sang, AM
   Liu, XJ
AF Yang, Xiaowei
   Chen, Hui
   Zhu, Manhui
   Zhu, Rongrong
   Qin, Bai
   Fang, Hongda
   Dai, Ming
   Sang, Aimin
   Liu, Xiaojuan
TI Up-Regulation of PKM2 Relates to Retinal Ganglion Cell Apoptosis After
   Light-Induced Retinal Damage in Adult Rats
SO CELLULAR AND MOLECULAR NEUROBIOLOGY
LA English
DT Article
DE PKM2; Light-induced retinal damage; RGCs; Apoptosis; Cyclin D1; ERK; Rat
ID PYRUVATE-KINASE M2; HYPOXIA-INDUCIBLE FACTOR-1; MACULAR DEGENERATION;
   NUCLEAR TRANSLOCATION; ALZHEIMERS-DISEASE; GLUCOSE-METABOLISM; SUNLIGHT
   EXPOSURE; EGFR ACTIVATION; CANCER-CELLS; CYCLIN D1
AB Pyruvate kinase isozyme type M2 (PKM2), a key glycolytic enzyme, which is involved in ATP generation and pyruvate production, participates in tumor metabolism, growth, and other multiple cellular processes. However, one attractive biological function of PKM2 is that it translocates to the nucleus and induces cell apoptosis. Recently, increased PKM2 has been found in age-related macular degeneration (AMD), but little is known regarding its function in the AMD pathophysiology. To investigate whether PKM2 participated in retinal degeneration, we performed a light-induced retinal damage model in adult rats. Western blot and immunohistochemistry analysis showed a significant up-regulation of PKM2 in retinal ganglion cells (RGCs) layer (GCL) after light exposure. Immunofluorescent labeling indicated that PKM2 located mainly in RGCs. Co-localization of PKM2 and active caspase-3 as well as TUNEL in RGCs suggested that PKM2 might participate in RGC apoptosis. In addition, the expression patterns of cyclin D1 and phosphorylated extracellular signal-regulated kinase (p-ERK) were parallel with that of PKM2. Furthermore, PKM2, cyclin D1, and active caspase-3 protein expression decreased by intravitreal injection of U0126, a highly selective inhibitor of MAPK/ERK kinase. Collectively, we hypothesized that PKM2 might participate in RGC apoptosis after light-induced retinal damage medicated by p-ERK through cycle re-entry mechanism.
C1 [Yang, Xiaowei; Chen, Hui; Zhu, Manhui; Zhu, Rongrong; Qin, Bai; Fang, Hongda; Dai, Ming; Sang, Aimin] Nantong Univ, Affiliated Hosp, Dept Ophthalmol, Nantong 226001, Jiangsu, Peoples R China.
   [Liu, Xiaojuan] Nantong Univ, Coll Med, Dept Pathogen Biol, Nantong 226001, Jiangsu, Peoples R China.
   [Yang, Xiaowei; Chen, Hui; Zhu, Manhui; Dai, Ming; Sang, Aimin; Liu, Xiaojuan] Nantong Univ, Coll Med, Jiangsu Prov Key Lab Inflammat & Mol Drug Target, Nantong 226001, Jiangsu, Peoples R China.
C3 Nantong University; Nantong University; Nantong University
RP Sang, AM (通讯作者)，Nantong Univ, Affiliated Hosp, Dept Ophthalmol, Nantong 226001, Jiangsu, Peoples R China.
EM sangam@ntu.edu.cn; ntlxj0305@163.com
FU National Natural Science Foundation of China [81401365]; Priority
   Academic Program Development of Jiangsu Higher Education Institutions
   (PAPD)
FX This work was supported in part by the National Natural Science
   Foundation of China (No. 81401365); a project funded by the Priority
   Academic Program Development of Jiangsu Higher Education Institutions
   (PAPD).
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NR 56
TC 11
Z9 11
U1 2
U2 23
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0272-4340
EI 1573-6830
J9 CELL MOL NEUROBIOL
JI Cell. Mol. Neurobiol.
PD NOV
PY 2015
VL 35
IS 8
BP 1175
EP 1186
DI 10.1007/s10571-015-0211-9
PG 12
WC Cell Biology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Neurosciences & Neurology
GA CT5WR
UT WOS:000362882300011
PM 25990228
DA 2022-11-30
ER

PT J
AU Nezhad, ZK
   Nagai, N
   Yamamoto, K
   Kaji, H
   Nishizawa, M
   Saya, H
   Nakazawa, T
   Abe, T
AF Nezhad, Zhaleh Kashkouli
   Nagai, Nobuhiro
   Yamamoto, Kotaro
   Kaji, Hirokazu
   Nishizawa, Matsuhiko
   Saya, Hideyuki
   Nakazawa, Toru
   Abe, Toshiaki
TI Application of clotrimazole via a novel controlled release device
   provides potent retinal protection
SO JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; DRUG-DELIVERY; MACULAR DEGENERATION; POSTERIOR
   SEGMENT; PHOTIC INJURY; LIGHT DAMAGE; PREVALENCE; PERMEABILITY;
   INHIBITORS; CELLS
AB Age-related macular degeneration is the leading cause of legal blindness among older individuals. Therefore, the development of new therapeutic agents and optimum drug delivery systems for its treatment are crucial. In this study, we investigate whether clotrimazole (CLT) is capable of protecting retinal cells against oxidative-induced injury and the possible inhibitory effect of a sustained CLT-release device against light-induced retinal damage in rats. In vitro results indicated pretreatment of immortalized retinal pigment epithelium cells (RPE-J cells) with 10-50 mu M CLT before exposure to oxygen/glucose deprivation conditions for 48 h decreased the extent of cell death, attenuated the percentage of reactive oxygen species-positive cells, and decreased the levels of cleaved caspase-3. The device consists of a separately fabricated reservoir, a CLT formulation, and a controlled release cover, which are made of poly(ethyleneglycol) dimethacrylate (PEGDM) and tri(ethyleneglycol) dimethacrylate (TEGDM). The release rate of CLT was successfully tuned by changing the ratio of PEGDM/TEGDM in the cover. In vivo results showed that use of a CLT-loaded device lessened the reduction of electroretinographic amplitudes after light exposure. These findings indicate that the application of a polymeric CLT-loaded device may be a promising method for the treatment of some retinal disorders.
C1 [Nezhad, Zhaleh Kashkouli; Nagai, Nobuhiro; Abe, Toshiaki] Tohoku Univ, Div Clin Cell Therapy, United Ctr Adv Res & Translat Med ART, Grad Sch Med,Aoba Ku, Sendai, Miyagi 9808575, Japan.
   [Yamamoto, Kotaro; Nakazawa, Toru] Tohoku Univ, Grad Sch Med, Dept Ophthalmol, Aoba Ku, Sendai, Miyagi 9808574, Japan.
   [Kaji, Hirokazu; Nishizawa, Matsuhiko] Tohoku Univ, Dept Bioengn & Robot, Grad Sch Engn, Aoba Ku, Sendai, Miyagi 9808579, Japan.
   [Saya, Hideyuki] Keio Univ, Div Gene Regulat, Inst Adv Med Res, Sch Med,Shinjuku Ku, Tokyo 1608582, Japan.
C3 Tohoku University; Tohoku University; Tohoku University; Keio University
RP Nakazawa, T (通讯作者)，Tohoku Univ, Grad Sch Med, Dept Ophthalmol, Aoba Ku, 1-1 Seiryo Machi, Sendai, Miyagi 9808574, Japan.
EM ntoru@oph.med.tohoku.ac.jp; toshi@oph.med.tohoku.ac.jp
RI Saya, Hideyuki/J-4325-2013; Kaji, Hirokazu/T-2219-2019
OI Kaji, Hirokazu/0000-0003-2566-4172; Saya, Hideyuki/0000-0001-6610-1902
FU KAKENHI from the Ministry of Education, Culture, Sports, Science, and
   Technology [23680054, 26560232, 15H03015]; Health Labour Sciences
   Research Grant from the Ministry of Health Labour and Welfare
   [H23-iryokiki-wakate-003, H23-kankaku-ippan-004,
   H24-nanchitoh-ippan-067]
FX This study was supported by KAKENHI (23680054, 26560232, 15H03015) from
   the Ministry of Education, Culture, Sports, Science, and Technology, and
   Health Labour Sciences Research Grant from the Ministry of Health Labour
   and Welfare (H23-iryokiki-wakate-003, H23-kankaku-ippan-004,
   H24-nanchitoh-ippan-067). We thank S. Ito for help with device mold
   preparation.
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NR 44
TC 5
Z9 5
U1 1
U2 4
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 SEP
PY 2015
VL 26
IS 9
AR 230
DI 10.1007/s10856-015-5561-9
PG 8
WC Engineering, Biomedical; Materials Science, Biomaterials
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Materials Science
GA CS0NC
UT WOS:000361756500003
PM 26335210
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Simcock, P
   Kingett, B
   Mann, N
   Reddy, V
   Park, J
AF Simcock, P.
   Kingett, B.
   Mann, N.
   Reddy, V.
   Park, J.
TI A safety audit of the first 10 000 intravitreal ranibizumab injections
   performed by nurse practitioners
SO EYE
LA English
DT Article
ID MACULAR DEGENERATION
AB Purpose To evaluate the safety of a nurse practitioner (NP)-delivered injection service for the treatment of wet age-related macular degeneration (wAMD) with ranibizumab.
   Methods An evaluation of medical staffing resources for providing an injection service for wAMD highlighted difficulties covering lists. An alternative strategy of an NP-delivered injection service was evaluated. Two suitable NPs with previous extensive experience in minor surgical procedures were identified. The department's senior vitreo-retinal consultant supervised the NP's training programme. A prospective safety audit was conducted for the first 5.5 years of the service.
   Results The NPs administered 10 006 injections in the first 5.5 years of the service (1 May 2008 to 8 October 2013). This represented 84.1% of the total injections performed during this period. Four patients developed presumed infectious endophthalmitis (1 was culture positive and 3 were culture negative). The incidence of post-injection endophthalmitis was 0.04%. There was no evidence of lens touch, retinal detachment, or systemic thrombo-embolic events.
   Conclusions Carefully selected and well-trained NPs are capable of delivering a safe and effective wAMD injection treatment service. This work demonstrates how such a service can be established and provides safety data that other units can use as a benchmark when evaluating their own practice.
C1 [Simcock, P.; Kingett, B.; Mann, N.; Reddy, V.; Park, J.] Royal Devon & Exeter NHS Fdn Trust, West England Eye Unit, Exeter EX2 5DW, Devon, England.
C3 University of Exeter
RP Simcock, P (通讯作者)，Royal Devon & Exeter NHS Fdn Trust, West England Eye Unit, Barrack Rd, Exeter EX2 5DW, Devon, England.
EM peter.simcock@nhs.net
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TC 26
Z9 26
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 OCT
PY 2014
VL 28
IS 10
BP 1161
EP 1164
DI 10.1038/eye.2014.153
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA AR7PG
UT WOS:000343771100003
PM 25033899
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Mihai, DM
   Washington, I
AF Mihai, D. M.
   Washington, I.
TI Vitamin A dimers trigger the protracted death of retinal pigment
   epithelium cells
SO CELL DEATH & DISEASE
LA English
DT Article
ID PHOTORECEPTOR OUTER SEGMENTS; MACULAR DEGENERATION; BINDING-PROTEIN;
   LIPOFUSCIN FLUOROPHORE; HUMAN RPE; BRUCHS MEMBRANE; VISUAL CYCLE; A2E;
   RETINOIDS; DISEASE
AB Cellular events responsible for the initiation of major neurodegenerative disorders of the eye leading to blindness, including age-related macular degeneration, Stargardt and Best diseases, are poorly understood. Accumulation of vitamin A dimers, such as N-retinylidene-N-retinylethanolamine (A2E) in the retinal pigment epithelium (RPE), is one of the earliest measurable events preceding retinal degeneration. However, the extent to which these dimers contribute to tissue degeneration is not clear. To determine if A2E could trigger morphological changes associated with the degenerating RPE and subsequent cell death, we evaluated its toxicity to cultured human RPE cells (ARPE-19). We show that A2E triggered the accumulation of debris followed by a protracted death. A2E was up to approximate to 14-fold more toxic than its precursor, retinaldehyde. Measurements reveal that the concentration of A2E in the aged human eye could exceed the concentration of all other retinoids, opening the possibility of A2E-triggered cell death by several reported mechanisms. Findings suggest that accumulation of vitamin A dimers such as A2E in the human eye might be responsible for the formation of ubiquitous RPE debris, an early indication of retinal degeneration, and that preventing or reducing the accumulation of vitamin A dimers is a prudent strategy to prevent blindness.
C1 [Mihai, D. M.; Washington, I.] Columbia Univ, Med Ctr, Dept Ophthalmol, New York, NY 10032 USA.
C3 Columbia University
RP Washington, I (通讯作者)，Columbia Univ, Med Ctr, Dept Ophthalmol, 160 Ft Washington Ave, New York, NY 10032 USA.
EM iw2101@columbia.edu
OI W, I/0000-0002-2238-7918
FU National Institute of Health, National Eye Institute [1R01EY021207-01];
   Brightfocus Foundation [M2010096]; NATIONAL EYE INSTITUTE [R01EY021207]
   Funding Source: NIH RePORTER
FX We thank the National Institute of Health, National Eye Institute (grant
   number 1R01EY021207-01) and the Brightfocus Foundation (grant number
   M2010096) for financial support.
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NR 67
TC 15
Z9 15
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD JUL
PY 2014
VL 5
AR e1348
DI 10.1038/cddis.2014.314
PG 11
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA AO8XO
UT WOS:000341639300039
PM 25058422
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Semeraro, F
   Romano, MR
   Danzi, P
   Angi, M
   Costagliola, C
AF Semeraro, F.
   Romano, M. R.
   Danzi, P.
   Angi, M.
   Costagliola, C.
TI INTRAVITREAL INFLIXIMAB FOR CHOROIDAL NEOVASCULARIZATION IN PATIENTS
   REFRACTORY TO CONVENTIONAL TREATMENTS
SO INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY
LA English
DT Article
DE choroid neovascularization; age-related macular degeneration; retinal
   angiomatous proliferation; central retina venous occlusion; infliximab;
   bevacizumab
AB The aim of the study is to evaluate the effectiveness and safety of intravitreal infliximab in the course of compassionate use in patients affected by choroidal neovascularization. This prospective interventional case series includes four eligible patients, affected by exudative age-related macular degeneration (2/4), retinal angiomatous proliferation (1/4) and central retinal vein occlusion (1/4), who were refractory to conventional treatments. The patients received a single intravitreal injection of 0.05 ml of reconstituted infliximab solution (20mg/ml). The main outcomes measure were changes in best-corrected visual acuity and central retinal thickness. Patients were evaluated at baseline, every week for the first month, then every two weeks, and on demand. Morphologic parameters improved after a single infliximab intravitreal injection. However, all patients developed acute uveitis in a period ranging from 4 to 7 weeks after treatment. Control of the intraocular inflammation was achieved with topical and systemic steroids in 3 patients, whereas in one case pars plana vitrectomy was needed. A single intravitreal injection of infliximab does not seem to improve the natural history of CNV from different aetiologies. However, all patients in our series developed a serious inflammatory response that required surgical management in one case. The intravitreal administration of infliximab is hence not safe and not recommended in clinical practice.
C1 [Semeraro, F.; Danzi, P.; Angi, M.] Univ Brescia, Dipartimento Oftalmol, Brescia, Italy.
   [Romano, M. R.] Ist Clin & Ric Humanitas, Dipartimento Oftalmol, Milan, Italy.
   [Romano, M. R.; Costagliola, C.] Univ Molise, Dipartimento Sci Salute, Campobasso, Italy.
C3 University of Brescia; University of Molise
RP Romano, MR (通讯作者)，IRCCS, Ist Clin & Ric Humanitas, Via Manzoni 56, I-20089 Milan, Italy.
EM mario.romano@humanitas.it
RI Costagliola, Ciro/G-5707-2012; Angi, Martina/C-9462-2017; Semeraro,
   Francesco fs/K-8667-2016
OI Costagliola, Ciro/0000-0001-8477-6188; Angi,
   Martina/0000-0003-2703-2056; Semeraro, Francesco fs/0000-0002-2275-4917
CR Arias L, 2010, RETINA-J RET VIT DIS, V30, P1601, DOI 10.1097/IAE.0b013e3181e9f942
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   Zeltser R, 2001, ARCH DERMATOL, V137, P893
NR 7
TC 6
Z9 6
U1 0
U2 1
PU BIOLIFE SAS
PI SILVA MARINA (TE)
PA VIA S STEFANO 39 BIS, 64029 SILVA MARINA (TE), ITALY
SN 0394-6320
J9 INT J IMMUNOPATH PH
JI Int. J. Immunopathol. Pharmacol.
PD JUL-SEP
PY 2013
VL 26
IS 3
BP 765
EP 768
DI 10.1177/039463201302600321
PG 4
WC Immunology; Pathology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology; Pathology; Pharmacology & Pharmacy
GA 237ZP
UT WOS:000325910500021
PM 24067474
DA 2022-11-30
ER

PT J
AU Supanji
   Shimomachi, M
   Hasan, MZ
   Kawaichi, M
   Oka, C
AF Supanji
   Shimomachi, Mari
   Hasan, Md. Zobaer
   Kawaichi, Masashi
   Oka, Chio
TI HtrA1 is induced by oxidative stress and enhances cell senescence
   through p38 MAPK pathway
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE HtrA1; age-related macular degeneration; AMD; p38 MAPK; retinal pigment
   epithelium; senescence; oxidative stress
ID RETINAL-PIGMENT EPITHELIUM; ACTIVATED PROTEIN-KINASES; SERINE-PROTEASE;
   MACULAR DEGENERATION; PROMOTER POLYMORPHISM; UP-REGULATION; EXPRESSION;
   GENE; SMOKING; RISK
AB Genetic predisposition and senescence of retinA1 pigment epithelium induced by oxidative stress are major contributors to age-related macular degeneration (AMD). Single-nucleotide polymorphisms in HTRA1 are strongly linked to the onset of AMD. In this study, we examine the role of HtrA1 in premature senescence and cell death induced by oxidative stress. HtrA1 mRNA and protein were up-regulated during premature senescence induced by H2O2 in both mouse embryonic fibroblasts (MEFs) and ARPE-19 cells. Expression of the senescence markers p21(CIP1/WAF1) and p16(INK4a), and SA-beta-gA1actosidase activity, were higher in HtrA1+/- MEFs than in HtrA1-/- MEFs. HtrA1+/+ and HtrA1+/- MEFs were more resistant than HtrA1-/- MEFs to H2O2-induced cell death. Activation of p38 MAPK by oxidative stress was quicker in HtrA1+/- MEFs than in HtrA1-/- MEFs. The effects of excess HtrA1 were examined by transient transfection of cells with HtrA1 expression vectors or by addition of recombinant proteins. Excess wild type HtrA1 accelerated premature senescence of MEFs and ARPE-19 cells, while the protease-inactive HtrA1 S328A did not. HtrA1-induced senescence was abrogated by inhibition of p38 MAPK. We conclude that HtrA1 is induced by oxidative stress and promotes premature cell senescence through p38 MAPK in a protease activity-dependent manner. (C) 2013 Elsevier Ltd. A1l rights reserved.
C1 [Supanji; Shimomachi, Mari; Hasan, Md. Zobaer; Kawaichi, Masashi; Oka, Chio] Nara Inst Sci & Technol, Div Gene Funct Anim, Nara 6300192, Japan.
   [Supanji] Gadjah Mada Univ, Dept Ophthalmol, Fac Med, Yogyakarta 55281, Indonesia.
C3 Nara Institute of Science & Technology; Gadjah Mada University
RP Oka, C (通讯作者)，Nara Inst Sci & Technol, Div Gene Funct Anim, 8916-5 Takayama, Nara 6300192, Japan.
EM coka@bs.naist.jp
OI Hasan, Md Zobaer/0000-0001-7174-4443; Supanji,
   Supanji/0000-0001-6911-9382
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NR 78
TC 36
Z9 39
U1 1
U2 11
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD JUL
PY 2013
VL 112
BP 79
EP 92
DI 10.1016/j.exer.2013.04.013
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 180OS
UT WOS:000321605100010
PM 23623979
DA 2022-11-30
ER

PT J
AU Amadi-Obi, A
   Yu, CR
   Dambuza, I
   Kim, SH
   Marrero, B
   Egwuagu, CE
AF Amadi-Obi, Ahjoku
   Yu, Cheng-Rong
   Dambuza, Ivy
   Kim, Sung-Hye
   Marrero, Bernadette
   Egwuagu, Charles E.
TI Interleukin 27 Induces the Expression of Complement Factor H (CFH) in
   the Retina
SO PLOS ONE
LA English
DT Article
ID TRANSCRIPTION FACTORS; MACULAR DEGENERATION; EPITHELIAL-CELLS; B-CELL;
   INFLAMMATION; UVEITIS; CYTOKINE; REGION; IRF8; PATHOGENESIS
AB Complement factor H (CFH) is a central regulator of the complement system and has been implicated in the etiology of age-related macular degeneration (AMD), a leading cause of blindness in the elderly. In view of previous studies showing that reduced expression of CFH in the retina is a risk factor for developing AMD, there is significant interest in understanding how CFH expression is regulated in the retina. In this study, we have shown that the anti-inflammatory cytokine, IL-27, induced CFH expression in mouse retinal cells and human retinal pigmented epithelial cells (RPE) through STAT1-mediated up-regulation of Interferon Regulatory Factor-1 (IRF-1) and IRF-8. We further show that cells in the ganglion and inner-nuclear layers of the retina constitutively express IRF-1 and IRF-8 and enhanced CFH expression in the retina during ocular inflammation correlated with significant increase in the expression of IRF-1, IRF-8 and IL-27 (IL-27p28 and Ebi3). Our data thus reveal a novel role of IL-27 in regulating complement activation through up-regulation of CFH and suggest that defects in IL-27 signaling or expression may contribute to the reduction of CFH expression in the retina of patients with AMD.
C1 [Amadi-Obi, Ahjoku; Yu, Cheng-Rong; Dambuza, Ivy; Kim, Sung-Hye; Marrero, Bernadette; Egwuagu, Charles E.] NEI, Mol Immunol Sect, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Eye Institute
   (NEI)
RP Egwuagu, CE (通讯作者)，NEI, Mol Immunol Sect, NIH, Bethesda, MD 20892 USA.
EM egwuaguc@nei.nih.gov
RI Dambuza, Ivy/M-2484-2019
OI Yu, Cheng-Rong/0000-0001-7246-0362
FU National Eye Institute; National Institutes of Health; NATIONAL EYE
   INSTITUTE [ZIAEY000372, ZIAEY000262] Funding Source: NIH RePORTER
FX The Intramural Research Programs of the National Eye Institute and
   National Institutes of Health provided funding for this research. The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
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   Xu HP, 2008, EXP EYE RES, V87, P319, DOI 10.1016/j.exer.2008.06.012
   Yang ZL, 2006, SCIENCE, V314, P992, DOI 10.1126/science.1133811
   Yu CR, 2011, INVEST OPHTH VIS SCI, V52, P6978, DOI 10.1167/iovs.11-7688
   Zhang JD, 2010, J BIOL CHEM, V285, P21269, DOI 10.1074/jbc.M110.100818
   Zhu JF, 2010, ANNU REV IMMUNOL, V28, P445, DOI 10.1146/annurev-immunol-030409-101212
   Zipfel PF, 2001, SEMIN THROMB HEMOST, V27, P191, DOI 10.1055/s-2001-15248
NR 43
TC 22
Z9 23
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 20
PY 2012
VL 7
IS 9
AR e45801
DI 10.1371/journal.pone.0045801
PG 9
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 014PT
UT WOS:000309388900101
PM 23029250
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Gamulescu, MA
   Helbig, H
AF Gamulescu, Maria-Andreea
   Helbig, Horst
TI Lack of Therapeutic Effect of Ranibizumab in Fellow Eyes After
   Intravitreal Administration
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; BEVACIZUMAB AVASTIN;
   CEREBROVASCULAR ACCIDENTS; PHARMACOKINETICS; INJECTIONS
AB Purpose: In patients with exudative age-related macular degeneration (AMD), intravitreal anti-vascular endothelial growth factor (VEGF) therapy can lead to stabilization and even improvement of visual acuity in the treated eye, as proven by multiple studies. Some case reports, however, also suspect an effect in the untreated fellow eye.
   Methods: Prospective case series of 26 patients treated with intravitreal ranibizumab injections in both eyes because of bilateral exudative AMD. In all patients, central retinal thickness (CRT) was measured by optical coherence tomography (OCT) in both eyes: before first treatment of the first eye, as well as 2 weeks later, just before first treatment of the second eye.
   Results: While mean CRT was significantly reduced in the treated first eye 2 weeks after intravitreal injection from 369.46 mu m (+/- 170.88) to 275.04 mu m (+/- 113.04), P = 0.0005, mean CRT in the untreated fellow eye increased significantly: from 349.08 mu m (+/- 118.93) to 403.46 mu m (+/- 173.14) 2 weeks later, P = 0.017.
   Conclusions: A therapeutic effect of ranibizumab in the untreated fellow eye could not be demonstrated. Overall, mean CRT in the untreated eye increased as would be expected for the normal course of this disease.
C1 [Gamulescu, Maria-Andreea; Helbig, Horst] Univ Eye Clin, Dept Ophthalmol, D-93051 Regensburg, Germany.
C3 University of Regensburg
RP Gamulescu, MA (通讯作者)，Univ Eye Clin, Dept Ophthalmol, Franz Josef Str Allee 11, D-93051 Regensburg, Germany.
EM gamulescu@eye-regensburg.de
FU Novartis Pharma GmbH
FX M.A. Gamulescu and H. Helbig both occasionally receive lecture fees from
   Novartis Pharma GmbH.
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NR 28
TC 19
Z9 19
U1 0
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1080-7683
EI 1557-7732
J9 J OCUL PHARMACOL TH
JI J. Ocular Pharmacol. Ther.
PD APR
PY 2010
VL 26
IS 2
BP 213
EP 216
DI 10.1089/jop.2009.0126
PG 4
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA 587KF
UT WOS:000276990000013
PM 20415626
DA 2022-11-30
ER

PT J
AU Wickham, L
   Lewis, GP
   Charteris, DG
   Fisher, SK
   Da Cruz, L
AF Wickham, L.
   Lewis, G. P.
   Charteris, D. G.
   Fisher, S. K.
   Da Cruz, L.
TI Histological analysis of retinas sampled during translocation surgery: a
   comparison with normal and transplantation retinas
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR TRANSLOCATION; PIGMENT EPITHELIUM; MULLER CELL; EXPRESSION;
   REATTACHMENT; DETACHMENT; PROLIFERATION; DEGENERATION; EVENTS; GFAP
AB Aims: To carry out a histopathological analysis of retinal specimens of patients undergoing translocation surgery for age-related macular degeneration (ARMD).
   Methods: A histopathological analysis, using confocal microscopy, was performed on six retinal specimens. Results were compared with those from two further retinal specimens, collected during RPE transplantation, to control for the effects of vitrectomy and ARMD. In addition, a third control specimen from a cadaver with no history of ophthalmic disease was also analysed.
   Results: In the translocation specimens, rods and cones were relatively well preserved but showed reduced density and outer segment length. In four specimens, there were focal areas of rod opsin redistribution to the inner segment, but this was not observed in the controls. Staining with calbindin was decreased in cones compared with controls but normal in horizontal and amacrine cells. Rod bipolar cells were mildly disorganised, and in one there was evidence of neurite sprouting. Glial fibrillar acidic protein was raised in both translocation and transplantation retinae but not in the cadaver control.
   Conclusions: In this study, there was little evidence of cellular injury following iatrogenic detachment; however, the rate of PVR following translocation surgery infers that cellular events set in motion may continue despite early reattachment.
C1 [Wickham, L.; Charteris, D. G.; Da Cruz, L.] Moorfields Eye Hosp, Vitreoretinal Dept, London EC1V 2PD, England.
   [Lewis, G. P.; Fisher, S. K.] Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA 93106 USA.
C3 University of London; University College London; Moorfields Eye Hospital
   NHS Foundation Trust; University of California System; University of
   California Santa Barbara
RP Wickham, L (通讯作者)，Moorfields Eye Hosp, Vitreoretinal Dept, City Rd, London EC1V 2PD, England.
EM louisa.wickham@moorfields.nhs.uk
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NR 24
TC 4
Z9 5
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 JUL
PY 2009
VL 93
IS 7
BP 969
EP 973
DI 10.1136/bjo.2008.146613
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 462HO
UT WOS:000267341900027
PM 19091855
DA 2022-11-30
ER

PT J
AU Fang, IM
   Yang, CH
   Yang, CM
   Chen, MS
AF Fang, I-Mo
   Yang, Chang-Hao
   Yang, Chung-May
   Chen, Muh-Shy
TI Comparative effects of fatty acids on proinflammatory gene
   cyclooxygenase 2 and inducible nitric oxide synthase expression in
   retinal pigment epithelial cells
SO MOLECULAR NUTRITION & FOOD RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Cyclooxygenase-2; Dietary fatty acid;
   Inducible nitric oxide synthase; Lutein
ID MACULAR DEGENERATION; DIETARY-FAT; CHOROIDAL NEOVASCULARIZATION;
   DOCOSAHEXAENOIC ACID; LINOLEIC-ACID; LUTEIN; RECEPTORS; PREVALENCE;
   MODULATION; HEALTH
AB Dietary fat modification is a promising approach to prevent age-related macular degeneration (AMD). However, which types of fatty acids carry a greater risk for AMD remains unclear. In this study, we compared the effects of 18-carbon fatty acids with different degrees of unsaturation on the expression of the proinflammatory genes cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) in human retinal pigment epithelium (RPE). Additionally, we investigated whether lutein could modulate these genes induced by fatty acids in RPE. Treatment with oleic acid, linoleic acid (LA), or linolenic acid increased the expression of iNOS and COX-2 genes and the production of prostaglandin E-2 and nitric oxide (NO) in RPE, whereas the saturated fatty acid stearic acid had little effect on these genes. Of the fatty acids Studied, LA had the greatest effects on the induction of these genes. Furthermore, LA also induced NF-kappa B transcriptional activation the most. Lutein inhibited LA-induced expression of COX-2 and iNOS in a dose-dependent manner. These data suggested that specific unsaturated fatty acids, particularly LA, can stimulate RPE cells to express proinflammatory genes, which may contribute to the pathogenesis of AMD. Lutein inhibited the expression of these genes induced by LA through blockade of NF-kappa B activation.
C1 [Fang, I-Mo; Yang, Chang-Hao; Yang, Chung-May; Chen, Muh-Shy] Natl Taiwan Univ Hosp, Dept Ophthalmol, Taipei, Taiwan.
   [Fang, I-Mo] Taipei City Hosp, Dept Ophthalmol, Zhongxiao Branch, Taipei, Taiwan.
C3 National Taiwan University; National Taiwan University Hospital; Taipei
   City Hospital
RP Yang, CH (通讯作者)，Natl Taiwan Univ Hosp, Dept Ophthalmol, 7 Chung Shan S Rd, Taipei, Taiwan.
EM DAH75@tpech.gov.tw
RI Yang, Chang-Hao/AAR-3759-2021; Yang, Chung-May/AAV-3737-2020
OI YANG, CHUNG-MAY/0000-0003-4082-420X; YANG, CHANG-HAO/0000-0002-4328-8716
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NR 45
TC 19
Z9 19
U1 0
U2 0
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 JUN
PY 2009
VL 53
IS 6
BP 739
EP 750
DI 10.1002/mnfr.200800220
PG 12
WC Food Science & Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Food Science & Technology
GA 462ZR
UT WOS:000267398200007
PM 19437483
DA 2022-11-30
ER

PT J
AU Roduit, R
   Schorderet, DF
AF Roduit, Raphael
   Schorderet, Daniel F.
TI MAP kinase pathways in UV-induced apoptosis of retinal pigment
   epithelium ARPE19 cells
SO APOPTOSIS
LA English
DT Article
DE retinal pigment epithelium cells; apoptosis; MAP kinases; ultra violet;
   AP-1; kinases inhibitors
ID ACTIVATED PROTEIN-KINASE; C-JUN; OXIDATIVE STRESS; GENE-EXPRESSION; JNK;
   PHOSPHORYLATION; AP-1; FOS; INVOLVEMENT; INHIBITORS
AB The retinal pigment epithelium (RPE) is constantly exposed to external injuries which lead to degeneration, dysfunction or loss of RPE cells. The balance between RPE cells death and proliferation may be responsible for several diseases of the underlying retina, including age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR). Signaling pathways able to control cells proliferation or death usually involve the MAPK (mitogen-activated protein kinases) pathways, which modulate the activity of transcription factors by phosphorylation. UV exposure induces DNA breakdown and causes cellular damage through the production of reactive oxygen species (ROS) leading to programmed cell death. In this study, human retinal pigment epithelial cells ARPE19 were exposed to 100 J/m(2) stop of UV-C and MAPK pathways were studied. We first showed the expression of the three major MAPK pathways. Then we showed that activator protein-1 (AP-1) was activated through phosphorylation of cJun and cFos, induced by JNK and p38, respectively. Specific inhibitors of both kinases decreased their respective activities and phosphorylation of their nuclear targets (cJun and cFos) and reduced UV-induced cell death. The use of specific kinases inhibitors may provide excellent tools to prevent RPE apoptosis specifically in RPE diseases involving ROS and other stress-related compounds such as in AMD.
C1 [Roduit, Raphael; Schorderet, Daniel F.] Inst Rech Ophthalmol, IRO, CH-1950 Sion, Switzerland.
   [Roduit, Raphael; Schorderet, Daniel F.] Univ Lausanne, Dept Ophthalmol, CH-1007 Lausanne, Switzerland.
   [Schorderet, Daniel F.] Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland.
C3 University of Lausanne; Swiss Federal Institutes of Technology Domain;
   Ecole Polytechnique Federale de Lausanne
RP Roduit, R (通讯作者)，Inst Rech Ophthalmol, IRO, Gd Champsec 64, CH-1950 Sion, Switzerland.
EM raphael.roduit@irovision.ch
RI Roduit, Raphael/AAC-3890-2021
OI Roduit, Raphael/0000-0001-7440-2799; Schorderet,
   Daniel/0000-0002-1331-504X
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NR 50
TC 96
Z9 110
U1 1
U2 15
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1360-8185
EI 1573-675X
J9 APOPTOSIS
JI Apoptosis
PD MAR
PY 2008
VL 13
IS 3
BP 343
EP 353
DI 10.1007/s10495-008-0179-8
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA 268IR
UT WOS:000253574000002
PM 18253836
OA Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Gatta, LB
   Vitali, M
   Zanola, A
   Venturelli, E
   Fenoglio, C
   Galimberti, D
   Scarpini, E
   Finazzi, D
AF Gatta, Luisa Benerini
   Vitali, Massimiliano
   Zanola, Alessandra
   Venturelli, Eliana
   Fenoglio, Chiara
   Galimberti, Daniela
   Scarpini, Elio
   Finazzi, Dario
TI Polymorphisms in the LOC387715/ARMS2 putative gene and the risk for
   Alzheimer's disease
SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS
LA English
DT Article
DE Alzheimer's disease, genetic study; risk factors; age-related macular
   degeneration; LOC387715/ARMS2 gene polymorphisms
ID AGE-RELATED MACULOPATHY; COMPLEMENT FACTOR-H; MACULAR DEGENERATION;
   CHROMOSOME 10Q26; AMYLOID-BETA; VARIANT; SUSCEPTIBILITY; LINKAGE; HTRA1;
   INCREASES
AB Background: Age-related macular degeneration (ARMD) and Alzheimer's disease (AD) are neurodegenerative disorders that share a high prevalence among elderly people, the extracellular deposition of beta-amyloid and the involvement of genetic factors in their aetiology. Genetic linkage with the chromosome regions 10q26 and 10q24-25 have been shown for ARMD and AD, respectively. The rs10490924 polymorphism, the major determinant of the 10q26 association with ARMD, determines the A69S substitution in the LOC387715/ARMS2 gene. Little information is available about the expression of the gene in humans. Methods: We analysed the expression of the gene by RT-PCR in the brain and we looked for nucleotide variations in the gene sequence by DHPLC. Results: We found specific gene transcripts in the hippocampus, cortex and cerebellum. The genetic analysis identified two other common variations, which determine the R3H change (rs10490923) and a premature stop codon (rs2736911), respectively. The analysis of their distribution in 213 AD patients and 149 controls revealed a trend for a reduced frequency of the variant allele of rs2736911 in AD patients (p = 0.038), with an odds ratio of 0.631. Conclusion: The LOC387715/ARMS2 gene is expressed in the human brain, and it may concur to the individual risk for AD. Copyright (C) 2008 S. Karger AG, Basel.
C1 [Gatta, Luisa Benerini; Vitali, Massimiliano; Zanola, Alessandra; Finazzi, Dario] Univ Brescia, Fac Med, Biochem Sect, IT-25123 Brescia, Italy.
   [Finazzi, Dario] Spedali Civil Brescia, Terzo Lab Anal Chim Clin, I-25125 Brescia, Italy.
   [Venturelli, Eliana; Fenoglio, Chiara; Galimberti, Daniela; Scarpini, Elio] Univ Milan, Dept Neurol Sci, Dino Ferrari Ctr, Fdn IRCCS Osped Maggiore Policlin, Milan, Italy.
C3 University of Brescia; Hospital Spedali Civili Brescia; IRCCS Ca Granda
   Ospedale Maggiore Policlinico; University of Milan
RP Finazzi, D (通讯作者)，Univ Brescia, Fac Med, Biochem Sect, Viale Europa 11, IT-25123 Brescia, Italy.
EM finazzi@med.unibs.it
RI finazzi, dario/GYV-1567-2022; Galimberti, Daniela/N-7209-2019; Scarpini,
   Elio/K-6547-2016
OI Galimberti, Daniela/0000-0002-9284-5953; Finazzi,
   Dario/0000-0001-5176-2839; Scarpini, Elio/0000-0002-6395-2119
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NR 28
TC 5
Z9 6
U1 0
U2 1
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 1420-8008
J9 DEMENT GERIATR COGN
JI Dement. Geriatr. Cogn. Disord.
PY 2008
VL 26
IS 2
BP 169
EP 174
DI 10.1159/000151050
PG 6
WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry
GA 356NM
UT WOS:000259784900010
PM 18688167
DA 2022-11-30
ER

PT J
AU Chen, X
   Liu, CT
   Zhang, M
   Zhang, H
AF Chen, Xiang
   Liu, Ching-Ti
   Zhang, Meizhuo
   Zhang, Heping
TI A forest-based approach to identifying gene and gene-gene interactions
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE age-related macular degeneration; genomewide association; haplotype;
   single-nucleotide polymorphism; tree and forest methods
ID GENOME-WIDE ASSOCIATION; FACTOR-H POLYMORPHISM; HAPLOTYPE INFERENCE;
   VARIANT; COMPONENTS; INCREASES; SMOKING; LOCI
AB Multiple genes, gene-by-gene interactions, and gene-by-environment interactions are believed to underlie most complex diseases. However, such interactions are difficult to identify. Although there have been recent successes in identifying genetic variants for complex diseases, it still remains difficult to identify gene-gene and gene-environment interactions. To overcome this difficulty, we propose a forest-based approach and a concept of variable importance. The proposed approach is demonstrated by simulation study for its validity and illustrated by a real data analysis for its use. Analyses of both real data and simulated data based on published genetic models show the effectiveness of our approach. For example, our analysis of a published data set on age-related macular degeneration (AMD) not only confirmed a known genetic variant (P value = 2E-6) for AMD, but also revealed an unreported haplotype surrounding single-nucleotide polymorphism (SNP) rs10272438 on chromosome 7 that was significantly associated with AMD (Pvalue = 0.0024). These significance levels are obtained after the consideration for a large number of SNPs. Thus, the importance of this work is twofold: it proposes a powerful and flexible method to identify high-risk haplotypes and their interactions and reveals a potentially protective variant for AMD.
C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA.
   Jiangxi Normal Univ, Jiangxi 330027, Peoples R China.
C3 Yale University; Jiangxi Normal University
RP Zhang, H (通讯作者)，Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, 333 Cedar St, New Haven, CT 06520 USA.
EM heping.zhang@yale.edu
RI Chen, Xiang/N-2524-2018
OI Chen, Xiang/0000-0002-2499-8261; Liu, Ching-Ti/0000-0002-0703-0742
FU EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN
   DEVELOPMENT [U01HD050062] Funding Source: NIH RePORTER; NATIONAL
   INSTITUTE ON DRUG ABUSE [R01DA016750, K02DA017713] Funding Source: NIH
   RePORTER
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NR 40
TC 67
Z9 69
U1 0
U2 6
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 DEC 4
PY 2007
VL 104
IS 49
BP 19199
EP 19203
DI 10.1073/pnas.0709868104
PG 5
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 239NU
UT WOS:000251525800009
PM 18048322
OA Bronze, Green Published
DA 2022-11-30
ER

PT J
AU Hirsch, JD
   Morello, C
   Singh, R
   Robbins, SL
AF Hirsch, Jan D.
   Morello, Candis
   Singh, Renu
   Robbins, Shira L.
TI Pharmacoeconomics of new medications for common chronic ophthalmic
   diseases
SO SURVEY OF OPHTHALMOLOGY
LA English
DT Review
DE age-related macular degeneration; cost-effectiveness; cost-minimization;
   cost-utility; dry eye disease; economics; glaucoma; pharmacoeconomic
   analyses
ID OPEN-ANGLE GLAUCOMA; OCULAR-HYPERTENSION-TREATMENT; COST-EFFECTIVENESS;
   PHOTODYNAMIC THERAPY; MACULAR DEGENERATION; BIMATOPROST 0.03-PERCENT;
   TOPICAL TREATMENTS; CLINICAL-OUTCOMES; ECONOMIC-ANALYSIS; BETA-BLOCKER
AB There is increasing pressure for medical care reimbursement to be linked to outcomes. New medications approved for glaucoma, age-related macular degeneration (AMD), and dry eye disease may, offer improved outcomes, but they have higher acquisition costs. This article reviews published pharmacoeconomic studies assessing the incremental change in outcomes achieved vs. the increased medication costs incurred. The different types of pharmacoeconomic evaluations are described. Identified pharmacoeconomic evaluations range front simple cost-consequence statements to more complex cost-utility analyses conducted across many healthcare systems. Notably missing in all analyses are the effects of improved treatment oil patient productivity. Although the diversity and small number of studies limit conclusions, there is sonic evidence that, the newer glaucoma medications, as a group, produce economic offsets such its reduced glaucoma surgeries and fewer physician Visits. Photodynamic therapy for AMD may be cost-effective when used early in patients with better visual acuity allowing cost-offsets over longer periods of time to lie considered. The single pharmacoeconomic analysis of topical cyclosporine for dry eye disease was only hypothesis-generating. Comprehensive studies that investigate clinical, economic, and humanistic outcomes for the patient and society are needed to adequately assess the comparative value of current and future oplithalmic medications.
C1 Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
   Univ Calif San Diego, Anne & Abraham Ratner Childrens Eye Ctr, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego
RP Hirsch, JD (通讯作者)，Skaggs Sch Pharm & Pharmaceut Sci, 9500 Gilman Dr,Mail Code 0714, La Jolla, CA 92093 USA.
RI Morello, Candis M./L-5519-2019
OI Morello, Candis M./0000-0001-6812-0234
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   2003, MED LETT DRUGS THER, V45, P42
NR 69
TC 6
Z9 6
U1 2
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 2007
VL 52
IS 6
BP 618
EP 633
DI 10.1016/j.survophthal.2007.08.017
PG 16
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 238OI
UT WOS:000251456700004
PM 18029270
DA 2022-11-30
ER

PT J
AU Munch, IC
   Sander, B
   Kessel, L
   Hougaard, JL
   Taarnhoj, NCBB
   Sorensen, TIA
   Kyvik, KO
   Larsen, M
AF Munch, Inger Christine
   Sander, Birgit
   Kessel, Line
   Hougaard, Jesper Leth
   Taarnhoj, Nina Charlotte Bille Brahe
   Sorensen, Thorkild I. A.
   Kyvik, Kirsten Ohm
   Larsen, Michael
TI Heredity of small hard drusen in twins aged 20-46 years
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID COMPLEMENT FACTOR-H; MACULAR DEGENERATION; CIGARETTE-SMOKING;
   BLOOD-PRESSURE; MACULOPATHY; HERITABILITY; POLYMORPHISM; DETERMINANT;
   PREVALENCE; LOC387715
AB PURPOSE. To examine the prevalence and heredity of small hard drusen in 220 healthy twins aged 20 - 46 years.
   METHODS. Grayscale digital fundus photography, four-field 50 degrees nonstereoscopic, in red-free illumination was performed in 58 pairs of monozygotic (MZ) twins and 52 pairs of dizygotic (DZ) twins as part of a detailed biometric characterization. Small hard drusen (diameters, < 63 mu m) were counted and graded by distribution type.
   RESULTS. Small hard drusen were present in 212 of the 220 subjects. Five or more drusen per eye were found in 89 subjects, in three patterns of distribution: scattered drusen (66 subjects), macular drusen (18 subjects), and stippled, innumerable drusen (5 subjects). When analyzed as a continuous trait, the heritability of small hard drusen was 63% (95% confidence interval [CI], 43% to 77%). More than 20 drusen per eye were found in 26 subjects, and the heritability of this phenotype was 99% (95% CI, 82% to 100%).
   CONCLUSIONS. Hard drusen are prevalent in young adults, and having more than 20 drusen per eye is a highly hereditary feature. Additional research is needed to determine whether the presence of small hard drusen correlates with the development of age-related macular degeneration later in life and to explore the relation to AMD genotypes.
C1 Univ Copenhagen, Dept Ophthalmol, Glostrup Hosp, DK-2600 Glostrup, Denmark.
   Univ Copenhagen Hosp, Inst Prevent Med, Danish Epidemiol Sci Ctr, DK-2100 Copenhagen, Denmark.
   Univ So Denmark, Danish Twin Reg, Odense, Denmark.
   Natl Eye Clin, Kennedy Inst, Hellerup, Denmark.
C3 University of Copenhagen; Aarhus University; University of Copenhagen;
   University of Southern Denmark
RP Munch, IC (通讯作者)，Univ Copenhagen, Dept Ophthalmol, Glostrup Hosp, Nordre Ringvej 57, DK-2600 Glostrup, Denmark.
EM icm@dadlnet.dk
RI Larsen, Michael/E-9620-2010; Munch, Inger Christine/E-9652-2010; Kyvik,
   Kirsten O/K-5680-2016
OI Larsen, Michael/0000-0002-5172-5891; Kyvik, Kirsten
   O/0000-0003-2981-0245; Kessel, Line/0000-0002-9375-1510; Hougaard,
   Jesper/0000-0002-8549-8885
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NR 36
TC 22
Z9 23
U1 0
U2 0
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD FEB
PY 2007
VL 48
IS 2
BP 833
EP 838
DI 10.1167/iovs.06-0529
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 129KV
UT WOS:000243729300048
PM 17251485
DA 2022-11-30
ER

PT J
AU Lutty, GA
   McLeod, DS
AF Lutty, GA
   McLeod, DS
TI Phosphatase enzyme histochemistry for studying vascular hierarchy,
   pathology, and endothelial cell dysfunction in retina and choroid
SO VISION RESEARCH
LA English
DT Article
DE phosphatase; enzyme histochemistry; adenosine diphosphatase; alkaline
   phosphatase; blood vessels
ID OXYGEN-INDUCED RETINOPATHY; DEGENERATION; MODEL; EYES
AB Phosphatase enzymes cleave an inorganic phosphate from a substrate. Phosphatase enzyme histochemistry followed by flat-embedding in glycol methacrylate is extremely useful in studying retinal and choroidal vascular development and loss, since only viable blood vessels have these enzyme activities. Sites of occlusion and remodeling can be identified and analysed, resulting in new insights into the cause of occlusion. The phosphatase activities are elevated in neovascularization making possible high resolution analysis of neovascularization, the feeder vessels, and the retinal milieu in which angiogenesis occurs. Adenosine diphosphatase (ADPase) catalyzes ADP to an inorganic phosphate plus adenosine monophosphate, preventing accumulation of ADP, one of the most potent stimuli for platelet aggregation. The ADPase technique can be used in any species but this report highlights its use in dog and human retinas. The ADPase technique has yielded important insights into vaso-occlusive and vasoproliferative processes in retinopathy of prematurity, sickle cell and diabetic retinopathies. The alkaline phosphatase flatembedding technique is useful in evaluating dog, cat, and human choroidal vasculatures. It has permitted quantification of the loss of choriocapillaris in diabetic choroidopathy and of the RPE and choriocapillaris in geographic atrophy and exudative age-related macular degeneration. (c) 2005 Elsevier Ltd. All rights reserved.
C1 Johns Hopkins Univ Hosp, Wilmer Ophthalmol Inst, 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, Baltimore, MD 21287 USA.
EM galutty@jhmi.edu
FU NEI NIH HHS [R01 EY009357-16, EY 01765, R01 EY009357, EY09357, P30
   EY001765, R01 EY016151, R01 EY016151-05] Funding Source: Medline; NHLBI
   NIH HHS [HL45922, R01 HL045922] Funding Source: Medline; NATIONAL EYE
   INSTITUTE [R01EY016151, P30EY001765, R01EY009357] Funding Source: NIH
   RePORTER; NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL045922]
   Funding Source: NIH RePORTER
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NR 16
TC 21
Z9 21
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0042-6989
J9 VISION RES
JI Vision Res.
PD DEC
PY 2005
VL 45
IS 28
BP 3504
EP 3511
DI 10.1016/j.visres.2005.08.022
PG 8
WC Neurosciences; Ophthalmology; Psychology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Ophthalmology; Psychology
GA 997FN
UT WOS:000234230600008
PM 16213000
OA Bronze, Green Accepted
DA 2022-11-30
ER

PT J
AU Calvo, MM
AF Calvo, MM
TI Lutein: A valuable ingredient of fruit and vegetables
SO CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
LA English
DT Review
DE lutein; health; fruit and vegetables concentration; quantification
   methods; lutein isomerization and degradation
ID PERFORMANCE LIQUID-CHROMATOGRAPHY; BEANS PHASEOLUS-VULGARIS; VIRGIN
   OLIVE OILS; LUNG-CANCER RISK; CAROTENOID COMPOSITION; BETA-CAROTENE;
   DIETARY CAROTENOIDS; MACULAR PIGMENT; VITAMIN-A;
   QUANTITATIVE-DETERMINATION
AB Lutein is a human serum carotenoid which is not synthesized by humans and thus must be obtained by the ingestion of food containing it such as fruits and vegetables. Lutein is present in different forms in those foods as all-trans-lutein, cis-lutein, epoxi-lutein, and lutein linked to proteins. It discusses if the intake of lutein or diets supplemented with lutein or diets rich in fruits and vegetables are important in the prevention of diseases like some cancers, cardiovascular diseases, etc., that may be affected by the antioxidant effect of lutein; or in the prevention of age-related macular degeneration and other eye diseases. The concentration of lutein in fruits and vegetables depends on the species. We've included the concentration of lutein in 74 species reported by, different authors since 1990. Currently the quantification of lutein is mainly performed by HPLC, but more investigations into a quantification method for lutein, lutein isomers, and epoxi-lutein are necessary. Improvement of lutein extraction methods is important as well. Methods commonly used in the vegetable and fruit industry like heat treatment, storage conditions, etc. can change lutein concentrations; other factors depend on the plant, for instance the variety, the stage of maturity, etc.
C1 CSIC, Inst Fermentac Ind, E-28006 Madrid, Spain.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto
   de Fermentaciones Industriales (IFI)
RP Calvo, MM (通讯作者)，CSIC, Inst Fermentac Ind, Juan Cierva 3, E-28006 Madrid, Spain.
EM mmcalvo@ifi.csic.es
RI Calvo, Marta/H-5841-2012
OI Calvo, Marta/0000-0002-7428-446X
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NR 172
TC 96
Z9 102
U1 7
U2 91
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1040-8398
EI 1549-7852
J9 CRIT REV FOOD SCI
JI Crit. Rev. Food Sci. Nutr.
PY 2005
VL 45
IS 7-8
BP 671
EP 696
DI 10.1080/10408690590957034
PG 26
WC Food Science & Technology; Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Food Science & Technology; Nutrition & Dietetics
GA 997TV
UT WOS:000234272600010
PM 16371334
DA 2022-11-30
ER

PT J
AU Janeschitz-Kriegl, L
   Cattaneo, M
   Scholl, HPN
AF Janeschitz-Kriegl, Lucas
   Cattaneo, Marco
   Scholl, Hendrik P. N.
TI Baseline Levels of Retinol-Binding Protein 4 and Vitamin A in Healthy
   Subjects, Stargardt Disease, and Geographic Atrophy Patients
SO OPHTHALMIC RESEARCH
LA English
DT Article
DE Retinal diseases; Retinol-binding protein 4; Stargardt disease;
   Age-related macular degeneration; Visual cycle
ID INSULIN-RESISTANCE; SERUM RETINOL; VISUAL CYCLE; LIPOFUSCIN;
   RETINOL-BINDING-PROTEIN-4; BISRETINOIDS; ACCUMULATION; PATHOGENESIS;
   OBESITY; RATIO
AB Introduction: The accumulation of lipofuscin is a hallmark in the pathogenesis of Stargardt disease type 1 (STGD1) and geographic atrophy (GA) secondary to age-related macular degeneration. Limiting lipofuscin accumulation by inhibiting the retinol-binding protein 4 (RBP4) is being explored as a potential treatment target for those diseases. In this study, we aimed to establish the concentration of RBP4 in the systemic circulation in different age cohorts of healthy individuals and to check if patients with STGD1 or GA may show abnormal RBP4 levels. Methods: Forty healthy subjects of various age-groups, 15 Stargardt patients, and 15 GA patients were included in the study. We measured RBP4 levels, serum retinol (SR) levels, complete blood count, and blood chemistry including liver function tests. Results: Mean RBP4 for all cohorts was 26,911.40 +/- 6,198.61 ng/mL, and mean SR 1.75 +/- 0.36 mu mol/L. Age was not found to significantly impact levels neither of RBP4 and SR nor of the RBP4-to-SR ratio. Also, the 2 patient groups showed similar blood levels to their age-matched controls. Conclusion: Serum RBP4 and SR do not appear to be affected by age in healthy individuals and remain within normal limits in both STGD1 and GA.
C1 [Janeschitz-Kriegl, Lucas; Scholl, Hendrik P. N.] Univ Basel, Dept Ophthalmol, Basel, Switzerland.
   [Janeschitz-Kriegl, Lucas; Cattaneo, Marco; Scholl, Hendrik P. N.] Inst Mol & Clin Ophthalmol Basel, Basel, Switzerland.
   [Cattaneo, Marco] Univ Basel, Dept Clin Res, Basel, Switzerland.
C3 University of Basel; University of Basel
RP Janeschitz-Kriegl, L (通讯作者)，Univ Basel, Dept Ophthalmol, Basel, Switzerland.; Janeschitz-Kriegl, L (通讯作者)，Inst Mol & Clin Ophthalmol Basel, Basel, Switzerland.
EM lucas.janeschitz@iob.ch
RI Cattaneo, Marco/I-5934-2013
OI Cattaneo, Marco/0000-0002-6610-8431
FU Stargazer pharmaceuticals
FX The research project was fully funded by Stargazer pharmaceuticals.
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NR 36
TC 0
Z9 0
U1 0
U2 1
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3747
EI 1423-0259
J9 OPHTHALMIC RES
JI Ophthalmic Res.
PD JUN
PY 2022
VL 65
IS 3
BP 351
EP 360
DI 10.1159/000522365
PG 10
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 2E4DS
UT WOS:000812179100013
PM 35108705
OA hybrid
DA 2022-11-30
ER

PT J
AU Gu, YJ
   Sun, Y
   Shang, JL
   Li, F
   Guan, BX
   Liu, JX
AF Gu, Yijun
   Sun, Yan
   Shang, Junliang
   Li, Feng
   Guan, Boxin
   Liu, Jin-Xing
TI Multi-Objective Artificial Bee Colony Algorithm Based on Scale-Free
   Network for Epistasis Detection
SO GENES
LA English
DT Article
DE artificial bee colony; scale-free network; epistasis detection; single
   nucleotide polymorphism; complex disease
ID OPTIMIZATION ALGORITHM; INFERENCE; GENE
AB In genome-wide association studies, epistasis detection is of great significance for the occurrence and diagnosis of complex human diseases, but it also faces challenges such as high dimensionality and a small data sample size. In order to cope with these challenges, several swarm intelligence methods have been introduced to identify epistasis in recent years. However, the existing methods still have some limitations, such as high-consumption and premature convergence. In this study, we proposed a multi-objective artificial bee colony (ABC) algorithm based on the scale-free network (SFMOABC). The SFMOABC incorporates the scale-free network into the ABC algorithm to guide the update and selection of solutions. In addition, the SFMOABC uses mutual information and the K2-Score of the Bayesian network as objective functions, and the opposition-based learning strategy is used to improve the search ability. Experiments were performed on both simulation datasets and a real dataset of age-related macular degeneration (AMD). The results of the simulation experiments showed that the SFMOABC has better detection power and efficiency than seven other epistasis detection methods. In the real AMD data experiment, most of the single nucleotide polymorphism combinations detected by the SFMOABC have been shown to be associated with AMD disease. Therefore, SFMOABC is a promising method for epistasis detection.
C1 [Gu, Yijun; Sun, Yan; Shang, Junliang; Li, Feng; Guan, Boxin; Liu, Jin-Xing] Qufu Normal Univ, Sch Comp Sci, Rizhao 276826, Peoples R China.
C3 Qufu Normal University
RP Shang, JL (通讯作者)，Qufu Normal Univ, Sch Comp Sci, Rizhao 276826, Peoples R China.
EM sunyan225@126.com; lifeng_10_28@163.com; jlshang@qfnu.edu.cn;
   lifeng_10_28@163.com; neuguanboxin@163.com; sdcavell@126.com
OI Junliang, Shang/0000-0002-8488-2228
FU National Natural Science Foundation of China [61972226, 61902216,
   61872220]
FX This work was supported by the National Natural Science Foundation of
   China (61972226, 61902216, and 61872220).
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PG 18
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA 1Q1GJ
UT WOS:000802444900001
PM 35627256
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Ray, SK
   Manz, SN
AF Ray, Subhransu K.
   Manz, Sarah N.
TI BRAIN HEALTH ASSESSMENT IN MACULAR DEGENERATION PATIENTS UNDERGOING
   INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTIONS (THE
   BHAM STUDY) An Interim Analysis
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE ARMD; cognitive impairment; intravitreal injections; VEGF
ID OPTIC-NERVE; BEVACIZUMAB; RANIBIZUMAB; AFLIBERCEPT
AB Purpose: After intravitreal injection, anti-vascular endothelial growth factor (VEGF) agents are found in the systemic circulation and can suppress systemic VEGF levels. Neuronal health and cognitive function in the central nervous system have been associated with normal physiological levels of VEGF expression. We wished to determine whether there was an association between cumulative anti-VEGF exposure and cognitive function. Methods: One hundred and seventy-five patients aged 65 to 85 with vision of at least 20/50 or better in one eye and a diagnosis of age-related macular degeneration took an iPad-based brain health assessment to determine their risk of mild cognitive impairment. The result for each patient was compared with the total number of anti-VEGF injections per individual patient. Patients were then stratified into groups with 0 injections (control), 1 to 9 injections, 10 to 20 injections, or greater than 20 injections. Results: The group of patients with more than 20 injections had a higher likelihood of mild cognitive impairment compared with the control group, with statistically significant worse mean Z-scores (P = 0.04). Conclusion: Our study is the first to associate worsening cognitive health with higher cumulative anti-VEGF injections. This study was not designed to show a causal link, but does suggest that additional investigation is warranted.
C1 [Ray, Subhransu K.; Manz, Sarah N.] Bay Area Retina Associates, 365 Lennon Lane,Suite 250, Walnut Creek, CA 94598 USA.
RP Ray, SK (通讯作者)，Bay Area Retina Associates, 365 Lennon Lane,Suite 250, Walnut Creek, CA 94598 USA.
EM sray@bayarearetina.com
FU Bay Area Retina Associates
FX The authors would like to thank Joel Kramer, PsyD, John Douglas French
   Alzheimer's Foundation Endowed Professor of Neuropsychology in
   Neurology, and Sabrina Erlhoff at the UCSF Department of Neurology for
   their guidance and for providing unrestricted access to the BHA
   protocol. The authors also wish to acknowledge the physicians at Bay
   Area Retina Associates for their intellectual and financial support.
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NR 23
TC 2
Z9 2
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 AUG
PY 2021
VL 41
IS 8
BP 1748
EP 1753
DI 10.1097/IAE.0000000000003066
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA WN5JN
UT WOS:000711803800022
PM 33346625
DA 2022-11-30
ER

PT J
AU Pishavar, E
   Luo, HR
   Bolander, J
   Atala, A
   Ramakrishna, S
AF Pishavar, Elham
   Luo, Hongrong
   Bolander, Johanna
   Atala, Antony
   Ramakrishna, Seeram
TI Nanocarriers, Progenitor Cells, Combinational Approaches, and New
   Insights on the Retinal Therapy
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Review
DE retinal pigment; Bruch&#8217; s membrane; nanofibrous scaffolds; drug
   delivery; stem cell therapy
AB Progenitor cells derived from the retinal pigment epithelium (RPECs) have shown promise as therapeutic approaches to degenerative retinal disorders including diabetic retinopathy, age-related macular degeneration and Stargardt disease. However, the degeneration of Bruch's membrane (BM), the natural substrate for the RPE, has been identified as one of the major limitations for utilizing RPECs. This degeneration leads to decreased support, survival and integration of the transplanted RPECs. It has been proposed that the generation of organized structures of nanofibers, in an attempt to mimic the natural retinal extracellular matrix (ECM) and its unique characteristics, could be utilized to overcome these limitations. Furthermore, nanoparticles could be incorporated to provide a platform for improved drug delivery and sustained release of molecules over several months to years. In addition, the incorporation of tissue-specific genes and stem cells into the nanostructures increased the stability and enhanced transfection efficiency of gene/drug to the posterior segment of the eye. This review discusses available drug delivery systems and combination therapies together with challenges associated with each approach. As the last step, we discuss the application of nanofibrous scaffolds for the implantation of RPE progenitor cells with the aim to enhance cell adhesion and support a functionally polarized RPE monolayer.
C1 [Pishavar, Elham] Mashhad Univ Med Sci, Pharmaceut Res Ctr, Pharmaceut Technol Inst, Mashhad 91735, Razavi Khorasan, Iran.
   [Pishavar, Elham; Bolander, Johanna; Atala, Antony] Wake Forest Sch Med, Wake Forest Inst Regenerat Med, Med Ctr Blvd, Winston Salem, NC 27157 USA.
   [Luo, Hongrong] Sichuan Univ, Engn Res Ctr Biomat, Chengdu 610064, Peoples R China.
   [Ramakrishna, Seeram] Natl Univ Singapore, Ctr Nanofibers & Nanotechnol, Singapore 117581, Singapore.
C3 Mashhad University Medical Science; Wake Forest University; Sichuan
   University; National University of Singapore
RP Atala, A (通讯作者)，Wake Forest Sch Med, Wake Forest Inst Regenerat Med, Med Ctr Blvd, Winston Salem, NC 27157 USA.; Ramakrishna, S (通讯作者)，Natl Univ Singapore, Ctr Nanofibers & Nanotechnol, Singapore 117581, Singapore.
EM pishavare931@mums.ac.ir; hluo@scu.edu.cn; jbolande@wakehealth.edu;
   aatala@wakehealth.edu; seeram@nus.edu.sg
RI Ramakrishna, Seeram/E-5186-2011; Ramakrishna, Seeram/AAY-4113-2021
OI Ramakrishna, Seeram/0000-0001-8479-8686; Ramakrishna,
   Seeram/0000-0001-8479-8686; Bolander, Johanna/0000-0002-6915-9509;
   Atala, Anthony/0000-0001-8186-2160
FU UParis-NUS 2020;  [ANR-18-IDEX-00001]
FX This research was funded by S.R.and H.L. Grant number
   [ANR-18-IDEX-00001], and the APC was funded by [UParis-NUS 2020].
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NR 100
TC 2
Z9 2
U1 1
U2 5
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD FEB
PY 2021
VL 22
IS 4
AR 1776
DI 10.3390/ijms22041776
PG 14
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA QP4WU
UT WOS:000623838200001
PM 33579019
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Feng, YF
   Zou, R
   Zhang, X
   Shen, MQ
   Chen, XP
   Wang, J
   Niu, WR
   Yuan, YZ
   Yuan, F
AF Feng, Yifan
   Zou, Rong
   Zhang, Xi
   Shen, Minqian
   Chen, Xiuping
   Wang, Jing
   Niu, Weiran
   Yuan, Yuanzhi
   Yuan, Fei
TI YAP promotes ocular neovascularization by modifying PFKFB3-driven
   endothelial glycolysis
SO ANGIOGENESIS
LA English
DT Article
DE Neovascularization; Endothelial cells; YAP; PFKFB3; Glycolysis
ID HIPPO SIGNALING PATHWAY; GROWTH-FACTOR THERAPY; CHOROIDAL
   NEOVASCULARIZATION; CELL METABOLISM; HYPOXIA; YAP/TAZ; HEALTH;
   PROLIFERATION; ANGIOGENESIS; ACTIVATION
AB Ocular neovascularization is the leading cause of vision impairment in a variety of ocular diseases, such as age-related macular degeneration and retinopathy of prematurity. Emerging studies have suggested that the yes-associated protein (YAP), a downstream effector of the Hippo pathway, is involved in the pathological angiogenesis, but the mechanism are largely unknown. Here, we demonstrated that hypoxic treatment triggered YAP expression and nuclear translocation in human umbilical vein endothelial cells (HUVECs). YAP acted as a transcriptional co-activator working together with transcriptional enhancer activator domain 1 (TEAD1) to binds the promoter of the key glycolytic regulator 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase3 (PFKFB3), and thereby increases PFKFB3 expression. Moreover, silencing of YAP inhibited glycolysis as well as proliferation, migration, sprouting and tube formation of HUVECs under hypoxia, all of which could be reversed by enforced expression of PFKFB3. Finally, our animal study also showed that intravitreal injection of small interfering RNA of YAP or PFKFB3 dramatically suppressed the neovascular growth in mouse models of choroidal neovascularization and oxygen-induced retinopathy. These findings provide new insights into a previously unrecognized effect of YAP on endothelial glycolysis and highlight the potential of targeting YAP/PFKFB3 axis in the treatment of ocular neovascularization.
C1 [Feng, Yifan; Zou, Rong; Zhang, Xi; Shen, Minqian; Chen, Xiuping; Wang, Jing; Niu, Weiran; Yuan, Yuanzhi; Yuan, Fei] Fudan Univ, Zhongshan Hosp, Dept Ophthalmol, 180 Fenglin Rd, Shanghai 200032, Peoples R China.
C3 Fudan University
RP Yuan, YZ; Yuan, F (通讯作者)，Fudan Univ, Zhongshan Hosp, Dept Ophthalmol, 180 Fenglin Rd, Shanghai 200032, Peoples R China.
EM yuan.yuanzhi@zs-hospital.sh.cn; yuanfei_zs@126.com
FU National Nature Science Foundation of China [81970817, 81873680,
   81800843, 81600735]; Excellent Youth Talent Program of Zhongshan
   Hospital [2017ZSYXQN30]
FX This study was supported by grants from the National Nature Science
   Foundation of China (No. 81970817, 81873680, 81800843 and 81600735) and
   the Excellent Youth Talent Program of Zhongshan Hospital (2017ZSYXQN30).
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NR 57
TC 12
Z9 12
U1 7
U2 8
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0969-6970
EI 1573-7209
J9 ANGIOGENESIS
JI Angiogenesis
PD AUG
PY 2021
VL 24
IS 3
BP 489
EP 504
DI 10.1007/s10456-020-09760-8
EA JAN 2021
PG 16
WC Peripheral Vascular Disease
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cardiovascular System & Cardiology
GA TL6NZ
UT WOS:000605097800001
PM 33400016
DA 2022-11-30
ER

PT J
AU Kim, HM
   Woo, SJ
AF Kim, Hyeong Min
   Woo, Se Joon
TI Ocular Drug Delivery to the Retina: Current Innovations and Future
   Perspectives
SO PHARMACEUTICS
LA English
DT Review
DE intravitreal injection; ocular drug delivery; nanoparticle; implant;
   hydrogel
AB Treatment options for retinal diseases, such as neovascular age-related macular degeneration, diabetic retinopathy, and retinal vascular disorders, have markedly expanded following the development of anti-vascular endothelial growth factor intravitreal injection methods. However, because intravitreal treatment requires monthly or bimonthly repeat injections to achieve optimal efficacy, recent investigations have focused on extended drug delivery systems to lengthen the treatment intervals in the long term. Dose escalation and increasing molecular weight of drugs, intravitreal implants and nanoparticles, hydrogels, combined systems, and port delivery systems are presently under preclinical and clinical investigations. In addition, less invasive techniques rather than intravitreal administration routes, such as topical, subconjunctival, suprachoroidal, subretinal, and trans-scleral, have been evaluated to reduce the treatment burden. Despite the latest advancements in the field of ophthalmic pharmacology, enhancing drug efficacy with high ocular bioavailability while avoiding systemic and local adverse effects is quite challenging. Consequently, despite the performance of numerous in vitro studies, only a few techniques have translated to clinical trials. This review discusses the recent developments in ocular drug delivery to the retina, the pharmacokinetics of intravitreal drugs, efforts to extend drug efficacy in the intraocular space, minimally invasive techniques for drug delivery to the retina, and future perspectives in this field.
C1 [Kim, Hyeong Min; Woo, Se Joon] Seoul Natl Univ, Bundang Hosp, Coll Med, Dept Ophthalmol, Seongnam 13620, South Korea.
C3 Seoul National University (SNU)
RP Woo, SJ (通讯作者)，Seoul Natl Univ, Bundang Hosp, Coll Med, Dept Ophthalmol, Seongnam 13620, South Korea.
EM hmkim3@gmail.com; sejoon1@snu.ac.kr
RI Woo, Se Joon/I-7357-2013
OI Woo, Se Joon/0000-0003-3692-7169
FU National Research Foundation of Korea (NRF) - Korean government (MSIT)
   [2020R1F1A1072795]; Bio & Medical Technology Development Program of the
   National Research Foundation (NRF) - Korean government (MSIT)
   [2018M3A9B5021319]
FX This work was supported by the National Research Foundation of Korea
   (NRF) grant funded by the Korean government (MSIT) (No.
   2020R1F1A1072795) and the Bio & Medical Technology Development Program
   of the National Research Foundation (NRF) funded by the Korean
   government (MSIT) (No. 2018M3A9B5021319); the funding organization had
   no role in the design or performance of this study.
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NR 202
TC 37
Z9 39
U1 23
U2 59
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 1999-4923
J9 PHARMACEUTICS
JI Pharmaceutics
PD JAN
PY 2021
VL 13
IS 1
AR 108
DI 10.3390/pharmaceutics13010108
PG 32
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA PW4ZJ
UT WOS:000610678700001
PM 33467779
OA Green Published, gold
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Rieveschl, NB
   Song, WL
   Li, A
   Conti, TF
   Hom, GL
   Tsai, GJ
   Conti, FF
   Babiuch, AS
   Singh, RP
AF Rieveschl, Nathaniel B.
   Song, Weilin
   Li, Ang
   Conti, Thais F.
   Hom, Grant L.
   Tsai, Grace J.
   Conti, Felipe F.
   Babiuch, Amy S.
   Singh, Rishi P.
TI Macular Atrophy Affecting Visual Outcomes in Patients Undergoing
   Anti-VEGF Treatment in Routine Clinical Practice
SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; GEOGRAPHIC ATROPHY; SUBGROUP ANALYSIS;
   DEGENERATION; RANIBIZUMAB; PROGRESSION; BEVACIZUMAB; PREVALENCE;
   SECONDARY; ANCHOR
AB BACKGROUND AND OBJECTIVE: To explore how baseline macular atrophy (MA) affects visual acuity (VA) in patients receiving intravitreal anti-vascular endothelial growth factor (VEGF) injections for neovascular age-related macular degeneration (nAMD).
   PATIENTS AND METHODS: A retrospective, case control series. Patients were grouped into three cohorts based on baseline spectral-domain optical coherence tomography image findings: foveal MA, non-foveal MA, and no MA. Outcomes were assessed at 1, 2, and 3 years following anti-VEGF therapy.
   RESULTS: No differences existed in MA growth between eyes with foveal and nonfoveal MA (0.89 mm 2 195% confidence interval (CI), 0.64-1.141 vs. 0.88 mm 2 [95% CI, 0.72-1.051) after adjusting for baseline lesion sizes at 3years. Foveal MA patients lost an average of 19.4 ETDRS letters (95% CI, -30.8 to -8.0) after 3 years. Nonfoveal MA patients gained an average of 1.1 ETDRS letters (95% CI, -6.8 to 9.0), and patients without MA averaged a gain of 9.7 ETDRS letters (95% CI, 5.5-14.0).
   CONCLUSION: In patients with nAMD receiving anti-VEGF in routine clinical practice, presence of baseline foveal MA was associated with significant vision loss.
C1 [Rieveschl, Nathaniel B.; Singh, Rishi P.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA.
   [Song, Weilin] Case Western Reserve Univ, Sch Med, Cleveland Clin, Lerner Coll Med, Cleveland, OH USA.
   [Song, Weilin; Li, Ang; Conti, Thais F.; Hom, Grant L.; Tsai, Grace J.; Conti, Felipe F.; Babiuch, Amy S.; Singh, Rishi P.] Cleveland Clin Fdn, Cole Eye Inst, 9500 Euclid Ave,Mail Code I-32, Cleveland, OH 44195 USA.
   [Conti, Thais F.; Hom, Grant L.; Conti, Felipe F.; Babiuch, Amy S.; Singh, Rishi P.] Cleveland Clin Fdn, Cole Eye Inst, Ctr Ophthalm Bioinformat, Cleveland, OH 44195 USA.
   [Tsai, Grace J.] Royal Coll Surgeons Ireland, Sch Med, Dublin, Ireland.
C3 Case Western Reserve University; Case Western Reserve University;
   Cleveland Clinic Foundation; Cleveland Clinic Foundation; Cleveland
   Clinic Foundation; Royal College of Surgeons - Ireland
RP Singh, RP (通讯作者)，Cleveland Clin Fdn, Cole Eye Inst, 9500 Euclid Ave,Mail Code I-32, Cleveland, OH 44195 USA.
EM singhr@ccf.org
OI Hom, Grant/0000-0002-1047-7609; Conti, Thais/0000-0003-4729-0706
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NR 22
TC 1
Z9 1
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 2020
VL 51
IS 2
BP 68
EP 75
DI 10.3928/23258160-20200129-01
PG 8
WC Ophthalmology; Surgery
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Surgery
GA KQ3EI
UT WOS:000516809400001
PM 32084278
DA 2022-11-30
ER

PT J
AU Palanisamy, K
   Raman, R
   Sulochana, KN
   Chidambaram, S
AF Palanisamy, Karthikka
   Raman, Rajiv
   Sulochana, Konerirajapuram Natarajan
   Chidambaram, Subbulakshmi
TI Adiponectin: A potential candidate for treating fibrosis in posterior
   segment of the eye
SO MEDICAL HYPOTHESES
LA English
DT Article
ID INDUCED CHOROIDAL NEOVASCULARIZATION; ENDOTHELIAL GROWTH-FACTOR;
   MICROVASCULAR COMPLICATIONS; EXPRESSION; PATHWAY; INHIBITION;
   FIBROBLAST; MECHANISMS; CYTOKINES; DISEASES
AB Fibrosis in ocular tissues causes severe visual deterioration and blindness in patients with glaucoma, cataract, age related macular degeneration (AMD) and diabetic retinopathy (DR). Currently available anti-fibrotic agents exhibit undesirous cytotoxic effects and thus prove ineffective to treat post-surgical fibrosis. Accordingly, there is a need to develop efficient and novel anti-fibrotic agents. Adiponectin (APN), an adipokine from adipocytes is increased in the aqueous and vitreous humor of the patients with micro-angiopathy and chronic inflammation. Furthermore, it is reported to be elevated in the subretinal fluid, vitreous and epiretinal membrane of patients with AMD, proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR) respectively.
   Since APN has anti-angiogenic activity and reduces VEGF levels, we hypothesize that APN might regulate the angio-fibrotic switch and drive the formation of fibrovascular membrane at advanced stages of AMD, PVR and PDR. Intriguingly, APN is shown to inhibit liver, cardiac and pulmonary fibrosis, yet it accelerates renal fibrosis. Therefore, the factors such as tissue and cell type, disease specific pathological milieu and the choice of APN receptor interaction could determine the pro- or anti-fibrotic nature of APN. We speculate that APN could play a profibrotic role in the posterior segment of the eye.
C1 [Palanisamy, Karthikka; Raman, Rajiv; Sulochana, Konerirajapuram Natarajan; Chidambaram, Subbulakshmi] Vis Res Fdn, KBIRVO, RS Mehta Jain Dept Biochem & Cell Biol, Chennai, India.
   [Palanisamy, Karthikka] SASTRA Univ, Sch Chem & Biotechnol, Thanjavur, India.
   [Chidambaram, Subbulakshmi] Pondicherry Univ, Dept Biochem & Mol Biol, Pondicherry 605014, India.
C3 Shanmugha Arts, Science, Technology & Research Academy (SASTRA);
   Pondicherry University
RP Chidambaram, S (通讯作者)，Pondicherry Univ, Dept Biochem & Mol Biol, Pondicherry 605014, India.
EM csubbulakshmi@gmail.com
RI Raman, Rajiv/A-7234-2009
OI Raman, Rajiv/0000-0001-5842-0233
FU DBT Neurobiology Taskforce [BT/PR5055/MED/30/761/2012]; DBT-RGYI
   [BT/PR15023/GBD/27/282/2010]
FX We thank DBT-RGYI BT/PR15023/GBD/27/282/2010 and DBT Neurobiology
   Taskforce "BT/PR5055/MED/30/761/2012" grants for supporting this work.
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NR 45
TC 5
Z9 5
U1 0
U2 2
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
   LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0306-9877
EI 1532-2777
J9 MED HYPOTHESES
JI Med. Hypotheses
PD FEB
PY 2019
VL 123
BP 9
EP 12
DI 10.1016/j.mehy.2018.12.005
PG 4
WC Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine
GA HL3DZ
UT WOS:000458594400004
PM 30696604
DA 2022-11-30
ER

PT J
AU Cai, H
   Gong, J
   Del Priore, LV
   Tezel, TH
   Fields, MA
AF Cai, Hui
   Gong, Jie
   Del Priore, Lucian V.
   Tezel, Tongap H.
   Fields, Mark A.
TI Culturing of Retinal Pigment Epithelial Cells on an Ex Vivo Model of
   Aged Human Bruch's Membrane
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Developmental Biology; Issue 134; Bruch's membrane; retinal pigment
   epithelial cells; geographic atrophy; age-related macular degeneration;
   ex vivo model; donor globe
ID MACULAR DEGENERATION; EXTRACELLULAR-MATRIX; IN-VITRO; REATTACHMENT;
   DRUSEN; LAYERS; REPOPULATION; RPE
AB Aside from vitamins and antioxidants recommended by the Age-Related Eye Disease Study, there is no effective therapy for "dry," or atrophic age-related macular degeneration (AMD) which represents 90% of the cases. Therapies are needed to slow or retard the development of geographic atrophy (GA), and understanding Bruch's membrane pathology is part of this process. Alterations in human Bruch's membrane precede the progression of AMD by contributing to the damage of retinal pigment epithelial (RPE) cells. Given the lack of sufficient animal models to study AMD, ex vivo models of aged human Bruch's membrane serve as a useful tool to study the behavior of RPE cells from immortalized and primary cell lines as well as RPE lines derived from induced pluripotent stem cells (iPSCs). Here, we present a detailed method that allows one to determine the effects of RPE cell behavior seeded on harvested human Bruch's membrane explants from human donors, including attachment, apoptosis and proliferation, ability to phagocytize photoreceptor outer segments, establishment of polarity, and gene expression. This assay provides an ex vivo model of aged Bruch's membrane to assess the functional characteristics of RPE cells when seeded on aged/compromised extracellular matrix.
C1 [Cai, Hui; Gong, Jie; Del Priore, Lucian V.; Fields, Mark A.] Yale Sch Med, Dept Ophthalmol & Visual Sci, New Haven, CT 06510 USA.
   [Tezel, Tongap H.] Columbia Univ, Sch Med, Edward S Harkness Eye Inst, New York, NY 10027 USA.
C3 Yale University; Columbia University
RP Fields, MA (通讯作者)，Yale Sch Med, Dept Ophthalmol & Visual Sci, New Haven, CT 06510 USA.
EM mark.fields@yale.edu
FU Research to Prevent Blindness, New York; Greater New York Center for
   Retinal Degenerative Disease Foundation Fighting Blindness; NATIONAL
   CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR001863] Funding
   Source: NIH RePORTER
FX This research is supported by Research to Prevent Blindness, New York,
   www.rpbusa.org, and the Greater New York Center for Retinal Degenerative
   Disease Foundation Fighting Blindness, www.blindness.org. The authors
   would like to thank Luanna Bartholomew, Ph.D., for her critical review
   of this manuscript.
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NR 25
TC 8
Z9 8
U1 0
U2 1
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 APR
PY 2018
IS 134
AR e57084
DI 10.3791/57084
PG 8
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA GS9OW
UT WOS:000444051300044
PM 29708536
OA Green Published
DA 2022-11-30
ER

PT J
AU Ho, CPS
   Lai, TYY
AF Ho, Christine P. S.
   Lai, Timothy Y. Y.
TI Pharmacotherapy for Choroidal Neovascularization Due to Uncommon Causes
SO CURRENT PHARMACEUTICAL DESIGN
LA English
DT Review
DE Choroidal neovascularization; anti-VEGF therapy; uveitis; angioid
   streak; central serous chorioretinopathy; pathologic myopia
ID PUNCTATE INNER CHOROIDOPATHY; CENTRAL SEROUS CHORIORETINOPATHY;
   GROWTH-FACTOR THERAPY; INTRAVITREAL BEVACIZUMAB INJECTION; VERTEPORFIN
   PHOTODYNAMIC THERAPY; TERM-FOLLOW-UP; MACULAR DEGENERATION; ANGIOID
   STREAKS; RANIBIZUMAB TREATMENT; SUBRETINAL FIBROSIS
AB Background: Choroidal neovascularization (CNV) in adults is most commonly associated with neovascular age-related macular degeneration (AMD) and pathologic myopia. Though less common, CNV can also develop from other conditions such as uveitis, central serous chorioretinopathy, angioid streaks, intraocular tumors, hereditary chorioretinal dystrophies, or can be idiopathic in origin. If left untreated, CNV may cause visual loss because of exudation of intraretinal or subretinal fluid, retinal or subretinal hemorrhage, or fibrosis involving the macula. It is well known that one of the main drivers of angiogenesis in CNV development is vascular endothelial growth factor (VEGF) and therefore inhibitors of VEGF might be an effective treatment for CNV.
   Methods: The goal of this review is to provide an overview and summary in the use of pharmacotherapy especially anti-VEGF therapy, in the treatment of CNV due to uncommon causes.
   Results: Results from uncontrolled case series and controlled clinical trials have reported good efficacy and safety in using anti-VEGF agents including bevacizumab, ranibizumab, aflibercept and ziv-aflibercept in the treatment of CNV due to uncommon causes. Anti-VEGF has also been used in combination with verteporfin PDT and anti-inflammatory agents for treating CNV of various causes.
   Conclusion: Pharmacotherapy with anti-VEGF agents is an effective treatment option for CNV due to uncommon etiologies.
C1 [Ho, Christine P. S.] Univ Hong Kong, Fac Med, Kowloon, Hong Kong, Peoples R China.
   [Lai, Timothy Y. Y.] Chinese Univ Hong Kong, Hong Kong Eye Hosp, Dept Ophthalmol & Visual Sci, Kowloon, 147K Argyle St, Hong Kong, Peoples R China.
   [Lai, Timothy Y. Y.] 2010 Retina & Macula Ctr, Kowloon, Hong Kong, Peoples R China.
C3 University of Hong Kong; Chinese University of Hong Kong
RP Lai, TYY (通讯作者)，Chinese Univ Hong Kong, Hong Kong Eye Hosp, Dept Ophthalmol & Visual Sci, Kowloon, 147K Argyle St, Hong Kong, Peoples R China.
EM tyylai@cuhk.edu.hk
RI Lai, Timothy Y Y/AAC-2120-2020
OI Lai, Timothy Y Y/0000-0002-7832-6428
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NR 126
TC 2
Z9 2
U1 1
U2 6
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 1381-6128
EI 1873-4286
J9 CURR PHARM DESIGN
JI Curr. Pharm. Design
PY 2018
VL 24
IS 41
BP 4882
EP 4895
DI 10.2174/1381612825666190206105943
PG 14
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA HP5XU
UT WOS:000461757700008
PM 30727875
DA 2022-11-30
ER

PT J
AU Gupta, V
   Gupta, VB
   Chitranshi, N
   Gangoda, S
   Wall, RV
   Abbasi, M
   Golzan, M
   Dheer, Y
   Shah, T
   Avolio, A
   Chung, R
   Martins, R
   Graham, S
AF Gupta, Vivek
   Gupta, Veer B.
   Chitranshi, Nitin
   Gangoda, Sumudu
   Wall, Roshana Vander
   Abbasi, Mojdeh
   Golzan, Mojtaba
   Dheer, Yogita
   Shah, Tejal
   Avolio, Alberto
   Chung, Roger
   Martins, Ralph
   Graham, Stuart
TI One protein, multiple pathologies: multifaceted involvement of amyloid
   beta in neurodegenerative disorders of the brain and retina
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Review
DE Neurotrophic factors; Mitochondrial impairment; Protein aggregation;
   Inflammation; Oxidative stress; Electroretinogram; Optical coherence
   tomography; Metal ions; Vascular dysfunction
ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; MACULAR DEGENERATION;
   NEUROTROPHIC FACTOR; PRECURSOR PROTEIN; MOUSE MODEL; APOLIPOPROTEIN-E;
   A-BETA; OXIDATIVE STRESS; GANGLION-CELLS
AB Accumulation of amyloid beta (A beta) and its aggregates in the ageing central nervous system is regarded synonymous to Alzheimer's disease (AD) pathology. Despite unquestionable advances in mechanistic and diagnostic aspects of the disease understanding, the primary cause of A beta accumulation as well as its in vivo roles remains elusive; nonetheless, the majority of the efforts to address pathological mechanisms for therapeutic development are focused towards moderating A beta accumulation in the brain. More recently, A beta deposition has been identified in the eye and is linked with distinct age-related diseases including age-related macular degeneration, glaucoma as well as AD. Awareness of the A beta accumulation in these markedly different degenerative disorders has led to an increasing body of work exploring overlapping mechanisms, a prospective biomarker role for A beta and the potential to use retina as a model for brain related neurodegenerative disorders. Here, we present an integrated view of current understanding of the retinal A beta deposition discussing the accumulation mechanisms, anticipated impacts and outlining ameliorative approaches that can be extrapolated to the retina for potential therapeutic benefits. Further longitudinal investigations in humans and animal models will determine retinal A beta association as a potential pathognomonic, diagnostic or prognostic biomarker.
C1 [Gupta, Vivek; Chitranshi, Nitin; Gangoda, Sumudu; Wall, Roshana Vander; Abbasi, Mojdeh; Golzan, Mojtaba; Dheer, Yogita; Avolio, Alberto; Chung, Roger; Graham, Stuart] Macquarie Univ, Fac Med & Hlth Sci, Sydney, NSW, Australia.
   [Gupta, Veer B.; Shah, Tejal; Martins, Ralph] Edith Cowan Univ, Sch Med Sci, Perth, WA, Australia.
   [Graham, Stuart] Univ Sydney, Save Sight Inst, Sydney, NSW, Australia.
C3 Macquarie University; Edith Cowan University; University of Sydney
RP Gupta, VB (通讯作者)，Edith Cowan Univ, Sch Med Sci, Perth, WA, Australia.
EM v.gupta@ecu.edu.au
RI Chung, Roger/ABF-8395-2020; Gupta, Vivek Kumar/AAB-8940-2022;
   Chitranshi, Nitin/AAK-8831-2020
OI Chitranshi, Nitin/0000-0002-6508-9865; Avolio,
   Alberto/0000-0002-8311-2010; Gupta, Veer/0000-0003-4989-0764; Golzan,
   Mojtaba/0000-0002-4479-3917; Gupta, Vivek/0000-0002-0202-7843; Dheer,
   Yogita/0000-0001-7525-7511; Graham, Stuart/0000-0001-7519-969X; Gangoda,
   Sumudu/0000-0001-9303-0812; Abbasi, Mojdeh/0000-0002-3641-0621; Shah,
   Tejal/0000-0002-3069-3835; Chung, Roger/0000-0002-9286-947X; Martins,
   Ralph/0000-0002-4828-9363
FU NHMRC; ORIA; MQRDG; Hillcrest foundation
FX We acknowledge research funding from the NHMRC, ORIA, MQRDG and
   Hillcrest foundation.
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NR 168
TC 44
Z9 44
U1 0
U2 35
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
EI 1420-9071
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD NOV
PY 2016
VL 73
IS 22
BP 4279
EP 4297
DI 10.1007/s00018-016-2295-x
PG 19
WC Biochemistry & Molecular Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Cell Biology
GA DY5SO
UT WOS:000385163300008
PM 27333888
DA 2022-11-30
ER

PT J
AU Reynolds, AL
   Alvarez, Y
   Sasore, T
   Waghorne, N
   Butler, CT
   Kilty, C
   Smith, AJ
   McVicar, C
   Wong, VHY
   Galvin, O
   Merrigan, S
   Osman, J
   Grebnev, G
   Sjolander, A
   Stitt, AW
   Kennedy, BN
AF Reynolds, Alison L.
   Alvarez, Yolanda
   Sasore, Temitope
   Waghorne, Nora
   Butler, Clare T.
   Kilty, Claire
   Smith, Andrew J.
   McVicar, Carmel
   Wong, Vickie H. Y.
   Galvin, Orla
   Merrigan, Stephanie
   Osman, Janina
   Grebnev, Gleb
   Sjolander, Anita
   Stitt, Alan W.
   Kennedy, Breandan N.
TI Phenotype-based Discovery of 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol as a
   Novel Regulator of Ocular Angiogenesis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CYSTEINYL LEUKOTRIENE RECEPTOR; OXYGEN-INDUCED RETINOPATHY; ENDOTHELIAL
   GROWTH-FACTOR; PATHOLOGICAL NEOVASCULARIZATION; RETINAL ANGIOGENESIS;
   ZEBRAFISH; MOUSE; D-4; RANIBIZUMAB; VASCULATURE
AB Retinal angiogenesis is tightly regulated to meet oxygenation and nutritional requirements. In diseases such as proliferative diabetic retinopathy and neovascular age-related macular degeneration, uncontrolled angiogenesis can lead to blindness. Our goal is to better understand the molecular processes controlling retinal angiogenesis and discover novel drugs that inhibit retinal neovascularization. Phenotype-based chemical screens were performed using the ChemBridge Diverset (TM) library and inhibition of hyaloid vessel angiogenesis in Tg(fli1: EGFP) zebrafish. 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol, (quininib) robustly inhibits developmental angiogenesis at 4-10 mu M in zebrafish and significantly inhibits angiogenic tubule formation in HMEC-1 cells, angiogenic sprouting in aortic ring explants, and retinal revascularization in oxygen-induced retinopathy mice. Quininib is well tolerated in zebrafish, human cell lines, and murine eyes. Profiling screens of 153 angiogenic and inflammatory targets revealed that quininib does not directly target VEGF receptors but antagonizes cysteinyl leukotriene receptors 1 and 2 (CysLT1-2) at micromolar IC50 values. In summary, quininib is a novel anti-angiogenic small-molecule CysLT receptor antagonist. Quininib inhibits angiogenesis in a range of cell and tissue systems, revealing novel physiological roles for CysLT signaling. Quininib has potential as a novel therapeutic agent to treat ocular neovascular pathologies and may complement current anti-VEGF biological agents.
C1 [Reynolds, Alison L.; Alvarez, Yolanda; Sasore, Temitope; Waghorne, Nora; Butler, Clare T.; Kilty, Claire; Smith, Andrew J.; Galvin, Orla; Merrigan, Stephanie; Grebnev, Gleb; Kennedy, Breandan N.] Univ Coll Dublin, Sch Biomol & Biomed Sci, Conway Inst, Dublin 4, Ireland.
   [McVicar, Carmel; Wong, Vickie H. Y.; Stitt, Alan W.] Queens Univ Belfast, Ctr Med Expt, Wellcome Wolfson Bldg,97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland.
   [Osman, Janina; Sjolander, Anita] Lund Univ, Skane Univ Hosp, Dept Translat Med, Div Cell & Expt Pathol, S-20502 Malmo, Sweden.
C3 University College Dublin; Queens University Belfast; Lund University;
   Skane University Hospital
RP Kennedy, BN (通讯作者)，Univ Coll Dublin, Conway Inst, UCD Sch Biomol & Biomed Sci, UCD Conway Inst F062, Dublin 4, Ireland.
EM brendan.kennedy@ucd.ie
RI Wong, Vickie/AAL-5158-2020; Stitt, Alan/A-9842-2009; kennedy,
   Breandan/H-5643-2019
OI Wong, Vickie/0000-0001-9356-7556; Stitt, Alan/0000-0002-8647-9918;
   kennedy, Breandan/0000-0001-7991-4689; Reynolds,
   Alison/0000-0002-3147-0094
FU Enterprise Ireland; Health Research Board Ireland; Science Foundation
   Ireland; Medical Research Council [G0801962] Funding Source:
   researchfish; The Sir Jules Thorn Charitable Trust [10JTA] Funding
   Source: researchfish; MRC [G0801962] Funding Source: UKRI
FX This work was supported by funding from an Enterprise Ireland proof of
   concept award, an Enterprise Ireland Commercialisation Fund award, a
   Health Research Board Ireland Health Research Award, and a Science
   Foundation Ireland Technology innovation development award. B. N. K. and
   Y. A. are authors on granted patent WO2012095836 A1. A. R., C. K., and
   B. N. K. are authors on patent filing WO2014012889 A1.
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NR 67
TC 26
Z9 26
U1 3
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 1
PY 2016
VL 291
IS 14
BP 7242
EP 7255
DI 10.1074/jbc.M115.710665
PG 14
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA DW2BJ
UT WOS:000383447600004
PM 26846851
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Winther, C
   Frisen, L
AF Winther, Christina
   Frisen, Lars
TI New rarebit vision test captures macular deficits hidden to acuity tests
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE age-related macular degeneration; macula; macular oedema; rarebit;
   vision test; visual acuity
ID AGE-RELATED MACULOPATHY; VISUAL-ACUITY; DEGENERATION; PERIMETRY
AB PurposeEvaluation of a new personal-computer-based vision test aimed for rapid and accurate assessment of macular conditions such as age-related macular degeneration (AMD).
   MethodsThe new test depends on segmented digits defined by rarebits, that is, receptive field-size bright dots briefly presented against a dark background. Digit size was fixed at 40x50min of arc. Digit positions were varied at random within a 4.6x3.5-degree test field. There were no fixation demands. The number of rarebits per digit segment could be varied between 3 (the minimum needed for veridical perception) and 128, in 11 preset steps. The test task was to find the smallest rarebit number required to recognize the test digits. Thirty-seven patients with various stages of AMD and 25 control subjects participated in the evaluation, which also included a standard acuity test.
   ResultsAnalysis of receiver operating characteristics indicated significantly better discrimination by the rarebit test. Rarebit numbers >16 appeared to reliably indicate the presence of oedema.
   ConclusionThe rarebit test appeared well suited for fine grading of vision in AMD. The simple set-up and the lack of fixation demands made for practicable examinations of short durations. The test is available for free on the Internet.
C1 [Winther, Christina; Frisen, Lars] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden.
C3 University of Gothenburg
RP Frisen, L (通讯作者)，White St 12 4 SU-S, SE-41345 Gothenburg, Sweden.
EM lars.frisen@gu.se
FU De Blindas Vanner, Gothenburg, Sweden
FX This work was supported by De Blindas Vanner, Gothenburg, Sweden. Author
   LF holds patents on the MacuBit test device mentioned in the text (but
   not used in this study).
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NR 21
TC 6
Z9 6
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
EI 1755-3768
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD AUG
PY 2015
VL 93
IS 5
BP 481
EP 485
DI 10.1111/aos.12659
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA CN5AC
UT WOS:000358440700036
PM 25604486
OA Bronze
DA 2022-11-30
ER

PT J
AU Cachafeiro, M
   Bemelmans, AP
   Samardzija, M
   Afanasieva, T
   Pournaras, JA
   Grimm, C
   Kostic, C
   Philippe, S
   Wenzel, A
   Arsenijevic, Y
AF Cachafeiro, M.
   Bemelmans, A-P
   Samardzija, M.
   Afanasieva, T.
   Pournaras, J-A
   Grimm, C.
   Kostic, C.
   Philippe, S.
   Wenzel, A.
   Arsenijevic, Y.
TI Hyperactivation of retina by light in mice leads to photoreceptor cell
   death mediated by VEGF and retinal pigment epithelium permeability
SO CELL DEATH & DISEASE
LA English
DT Article
DE neurodegeneration; photoreceptor; VEGF; retina; gene therapy
ID ENDOTHELIAL GROWTH-FACTOR; SINGLE-CHAIN ANTIBODY; CHOROIDAL
   NEOVASCULARIZATION; MACULAR DEGENERATION; INDUCED APOPTOSIS; OXIDATIVE
   STRESS; IN-VITRO; ANGIOGENESIS; BARRIER; RAT
AB Light toxicity is suspected to enhance certain retinal degenerative processes such as age-related macular degeneration. Death of photoreceptors can be induced by their exposure to the visible light, and although cellular processes within photoreceptors have been characterized extensively, the role of the retinal pigment epithelium (RPE) in this model is less well understood. We demonstrate that exposition to intense light causes the immediate breakdown of the outer blood-retinal barrier (BRB). In a molecular level, we observed the slackening of adherens junctions tying up the RPE and massive leakage of albumin into the neural retina. Retinal pigment epithelial cells normally secrete vascular endothelial growth factor (VEGF) at their basolateral side; light damage in contrast leads to VEGF increase on the apical side - that is, in the neuroretina. Blocking VEGF, by means of lentiviral gene transfer to express an anti-VEGF antibody in RPE cells, inhibits outer BRB breakdown and retinal degeneration, as illustrated by functional, behavioral and morphometric analysis. Our data show that exposure to high levels of visible light induces hyperpermeability of the RPE, likely involving VEGF signaling. The resulting retinal edema contributes to irreversible damage to photoreceptors. These data suggest that anti-VEGF compounds are of therapeutic interest when the outer BRB is altered by retinal stresses.
C1 [Cachafeiro, M.; Bemelmans, A-P; Kostic, C.; Philippe, S.; Arsenijevic, Y.] Univ Lausanne, Jules Gonin Eye Hosp, Unit Gene Therapy & Stem Cell Biol, Lausanne, Switzerland.
   [Bemelmans, A-P] Univ Paris 06, INSERM, U968, CNRS,UMR 7210,Inst Vis,UM80, Paris, France.
   [Samardzija, M.; Grimm, C.; Wenzel, A.] Univ Zurich, Dept Ophthalmol, Lab Retinal Cell Biol, Zurich, Switzerland.
   [Afanasieva, T.] Univ Zurich Hosp, Dept Pathol, Div Canc Res, CH-8091 Zurich, Switzerland.
   [Pournaras, J-A] Univ Lausanne, Jules Gonin Eye Hosp, Vitreoretinal Surg Unit, Zurich, Switzerland.
C3 University of Lausanne; Centre National de la Recherche Scientifique
   (CNRS); CNRS - National Institute for Biology (INSB); Institut National
   de la Sante et de la Recherche Medicale (Inserm); UDICE-French Research
   Universities; Sorbonne Universite; Universite Paris Cite; University of
   Zurich; University of Zurich; University Zurich Hospital; University of
   Lausanne
RP Arsenijevic, Y (通讯作者)，Hop Ophtalm Jules Gonin, Unit Gene Therapy & Stem Cell Biol, Ave France 15, CH-1004 Lausanne, Switzerland.
EM alexis.bemelmans@cea.fr; yvan.arsenijevic@fa2.ch
RI Bemelmans, Alexis-Pierre/H-4476-2019; Samardzija, Marijana/B-9245-2008
OI Bemelmans, Alexis-Pierre/0000-0001-7605-5225; Samardzija,
   Marijana/0000-0003-0991-4653; Arsenijevic, Yvan/0000-0001-6960-1291;
   Kostic, Corinne/0000-0003-1006-9733; Grimm,
   Christian/0000-0001-9318-4352
FU "Association Francaise contre les Myopthies" (AFM); Provisu Foundation;
   Swiss National Science Foundation; OpenEyes foundation
FX We thank Verene Pignat, Dana Wanner and Meriem Tekaya for their
   excellent technical supports. This work was supported by "Association
   Francaise contre les Myopthies" (AFM), the Provisu Foundation, the Swiss
   National Science Foundation, the OpenEyes foundation.
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NR 56
TC 41
Z9 46
U1 5
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD AUG
PY 2013
VL 4
AR e781
DI 10.1038/cddis.2013.303
PG 11
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA 214PK
UT WOS:000324146000038
PM 23990021
OA Green Published, gold, Green Accepted
DA 2022-11-30
ER

PT J
AU Vera, DMA
   Haynes, MH
   Ball, AR
   Dai, TH
   Astrakas, C
   Kelso, MJ
   Hamblin, MR
   Tegos, GP
AF Adolfo Vera, Domingo Mariano
   Haynes, Mark H.
   Ball, Anthony R.
   Dai, Tianhong
   Astrakas, Christos
   Kelso, Michael J.
   Hamblin, Michael R.
   Tegos, George P.
TI Strategies to Potentiate Antimicrobial Photoinactivation by Overcoming
   Resistant Phenotypes
SO PHOTOCHEMISTRY AND PHOTOBIOLOGY
LA English
DT Review
ID MEDIATED PHOTODYNAMIC THERAPY; PSEUDOMONAS-AERUGINOSA BIOFILMS;
   GRAM-NEGATIVE BACTERIA; N-METHYL-PYRIDYL; STAPHYLOCOCCUS-AUREUS;
   MULTIDRUG TRANSPORTER; CRYSTAL-STRUCTURE; EFFLUX PUMP; IN-VITRO; ABC
   TRANSPORTERS
AB Conventional antimicrobial strategies have become increasingly ineffective due to the emergence of multidrug resistance among pathogenic microorganisms. The need to overcome these deficiencies has triggered the exploration of alternative treatments and unconventional approaches towards controlling microbial infections. Photodynamic therapy (PDT) was originally established as an anticancer modality and is currently used in the treatment of age-related macular degeneration. The concept of photodynamic inactivation requires cell exposure to light energy, typically wavelengths in the visible region that causes the excitation of photosensitizer molecules either exogenous or endogenous, which results in the production of reactive oxygen species (ROS). ROS produce cell inactivation and death through modification of intracellular components. The versatile characteristics of PDT prompted its investigation as an anti-infective discovery platform. Advances in understanding of microbial physiology have shed light on a series of pathways, and phenotypes that serve as putative targets for antimicrobial drug discovery. Investigations of these phenotypic elements in concert with PDT have been reported focused on multidrug efflux systems, biofilms, virulence and pathogenesis determinants. In many instances the results are promising but only preliminary and require further investigation. This review discusses the different antimicrobial PDT strategies and highlights the need for highly informative and comprehensive discovery approaches.
C1 [Tegos, George P.] Univ New Mexico, Sch Med, Dept Pathol, Ctr Mol Discovery, Albuquerque, NM 87131 USA.
   [Adolfo Vera, Domingo Mariano] Univ Nacl Mar del Plata, Fac Ciencias Exactas & Nat, Dept Chem, Mar Del Plata, Buenos Aires, Argentina.
   [Ball, Anthony R.] Toxikon Corp, Bedford, MA USA.
   [Tegos, George P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA.
   [Dai, Tianhong; Hamblin, Michael R.; Tegos, George P.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
   [Astrakas, Christos] Democritus Univ, Thrace Med Sch, Div Internal Med, Alexandroupolis, Greece.
   [Kelso, Michael J.] Univ Wollongong, Sch Chem, Wollongong, NSW 2522, Australia.
   [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA.
C3 University of New Mexico; National University of Mar del Plata; Harvard
   University; Harvard Medical School; Massachusetts General Hospital;
   Harvard University; Harvard Medical School; Democritus University of
   Thrace; University of Wollongong; Harvard University
RP Tegos, GP (通讯作者)，Univ New Mexico, Sch Med, Dept Pathol, Ctr Mol Discovery, Albuquerque, NM 87131 USA.
EM gtegos@salud.unm.edu
RI Hamblin, Michael R/H-2758-2019; Dai, Tianhong/P-5961-2018; Vera,
   Mariano/AAI-1889-2020; Hamblin, Mike/AAB-2511-2022
OI Hamblin, Michael R/0000-0001-6431-4605; Dai,
   Tianhong/0000-0001-8960-8896; Vera, Mariano/0000-0003-1433-4741; Kelso,
   Michael/0000-0001-7809-6637; Ball, Anthony/0000-0002-3212-269X
FU NIH [5U54MH084690-02, RO1 AI050875]; US Air Force MFEL
   [FA9550-04-1-0079]; Bullock-Wellman Fellowship Award; Airlift Research
   Foundation [109421]; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS
   DISEASES [R01AI050875] Funding Source: NIH RePORTER; NATIONAL INSTITUTE
   OF MENTAL HEALTH [U54MH084690] Funding Source: NIH RePORTER
FX George P. Tegos is supported by the NIH (grant 5U54MH084690-02).
   Research conducted in the Hamblin Laboratory was supported by NIH (RO1
   AI050875 to MRH) and US Air Force MFEL Program (FA9550-04-1-0079). TD
   was partially supported by a Bullock-Wellman Fellowship Award and an
   Airlift Research Foundation Extremity Trauma Research Grant (grant
   109421).
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NR 127
TC 91
Z9 95
U1 2
U2 42
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 MAY-JUN
PY 2012
VL 88
IS 3
BP 499
EP 511
DI 10.1111/j.1751-1097.2012.01087.x
PG 13
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 935EH
UT WOS:000303501300003
PM 22242675
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU Barot, M
   Gokulgandhi, MR
   Mitra, AK
AF Barot, Megha
   Gokulgandhi, Mitan R.
   Mitra, Ashim K.
TI Mitochondrial Dysfunction in Retinal Diseases
SO CURRENT EYE RESEARCH
LA English
DT Review
DE Mitochondria; Diabetic retinopathy; Glaucoma; Retinal degeneration;
   Age-related macular degeneration
ID PIGMENT EPITHELIAL-CELLS; COMPLEMENT FACTOR-H; OXIDATIVE STRESS; DNA
   DAMAGE; MACULAR DEGENERATION; EXPERIMENTAL GALACTOSEMIA; TARGETING
   ANTIOXIDANTS; SUPEROXIDE-DISMUTASE; DIABETIC-RETINOPATHY; L-CARNITINE
AB The mitochondrion is a vital intracellular organelle for retinal cell function and survival. There is growing confirmation to support an association between mitochondrial dysfunction and a number of retinal degenerations. Investigations have also unveiled mitochondrial genomic instability as one of the contributing factors for age-related retinal pathophysiology. This review highlights the role of mitochondrial dysfunction originating from oxidative stress in the etiology of retinal diseases including diabetic retinopathy, glaucoma and age-related macular degeneration (AMD). Moreover, mitochondrial DNA (mtDNA) damage associated with AMD due to susceptibility of mtDNA to oxidative damage and failure of mtDNA repair pathways is also highlighted in this review. The susceptibility of neural retina and retinal pigment epithelium (RPE) mitochondria to oxidative damage with ageing appears to be a major factor in retinal degeneration. It thus appears that the mitochondrion is a weak link in the antioxidant defenses of retinal cells. In addition, failure of mtDNA repair pathways can also specifically contribute towards pathogenesis of AMD. This review will further summarize the prospective role of mitochondria targeting therapeutic agents for the treatment of retinal disease. Mitochondria based drug targeting to diminish oxidative stress or promote repair of mtDNA damage may offer potential alternatives for the treatment of various retinal degenerative diseases.
C1 [Mitra, Ashim K.] Univ Missouri, Sch Pharm, Div Pharmaceut Sci, Kansas City, MO 64108 USA.
C3 University of Missouri System; University of Missouri Kansas City
RP Mitra, AK (通讯作者)，Univ Missouri, Sch Pharm, Div Pharmaceut Sci, 2464 Charlotte St, Kansas City, MO 64108 USA.
EM mitraa@umkc.edu
FU NIH [RO1 EY 09171-16, RO1 EY 10659-14]; NATIONAL EYE INSTITUTE
   [R01EY010659, R01EY009171] Funding Source: NIH RePORTER
FX This work has been supported by NIH grants RO1 EY 09171-16 and RO1 EY
   10659-14.
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NR 86
TC 128
Z9 136
U1 0
U2 16
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0271-3683
EI 1460-2202
J9 CURR EYE RES
JI Curr. Eye Res.
PD DEC
PY 2011
VL 36
IS 12
BP 1069
EP 1077
DI 10.3109/02713683.2011.607536
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 847NR
UT WOS:000296980100001
PM 21978133
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Bartling, H
   Wanger, P
   Martin, L
AF Bartling, Herman
   Wanger, Peter
   Martin, Lene
TI Automated quality evaluation of digital fundus photographs
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE automatic; computerized; digital fundus photography; quality evaluation
ID DIABETIC-RETINOPATHY; IMAGES
AB Purpose:
   Retinal images acquired by means of digital photography are often used for evaluation and documentation of the ocular fundus, especially in patients with diabetes, glaucoma or age-related macular degeneration. The clinical usefulness of an image is highly dependent on its quality. We set out to develop and evaluate an automatic method of evaluating the quality of digital fundus photographs.
   Methods:
   A method for making a numerical quantification of image sharpness and illumination was developed using Matlab (TM) image analysis functions. Based on their sharpness and illumination measures, 1000 fundus photographs, randomly selected from a clinical database, were assigned to four predefined quality groups (not acceptable, acceptable, good, very good). Six independent observers, comprising three experienced ophthalmologists and three ophthalmic nurses with extensive experience in fundus image acquisition, classified a selection of 100 of these images into the corresponding quality groups.
   Results:
   Automatic quality evaluation was more sensitive than evaluation by human observers in terms of ability to discriminate between good and very good images. The median concordance between the six human observers and the automatic evaluation was substantial (kappa = 0.64).
   Conclusions:
   The proposed method provides an objective quality assessment of digital fundus photographs which agrees well with evaluations made by qualified human observers and which may be useful in clinical practice.
C1 [Martin, Lene] St Eriks Eye Hosp, Karolinska Inst, Dept Clin Neurosci Ophthalmol & Vis, SE-11282 Stockholm, Sweden.
C3 Karolinska Institutet
RP Martin, L (通讯作者)，St Eriks Eye Hosp, Karolinska Inst, Dept Clin Neurosci Ophthalmol & Vis, SE-11282 Stockholm, Sweden.
EM lene.martin@ki.se
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   WU P, 2005, HPL200514
NR 23
TC 41
Z9 45
U1 1
U2 13
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
EI 1755-3768
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD SEP
PY 2009
VL 87
IS 6
BP 643
EP 647
DI 10.1111/j.1755-3768.2008.01321.x
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 488LF
UT WOS:000269350500009
PM 19719806
DA 2022-11-30
ER

PT J
AU Chen, M
   Muckersie, E
   Robertson, M
   Forrester, JV
   Xu, HP
AF Chen, Mei
   Muckersie, Elizabeth
   Robertson, Marie
   Forrester, John V.
   Xu, Heping
TI Up-regulation of complement factor B in retinal pigment epithelial cells
   is accompanied by complement activation in the aged retina
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE retina; aging; age-related macular degeneration; complement activation;
   complement factor B; inflammation; cytokines; retinal pigment epithelial
   cell
ID PHOTORECEPTOR OUTER SEGMENTS; GEOGRAPHIC ATROPHY FORM; FACTOR-H
   POLYMORPHISM; MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION;
   DRUSEN; INFLAMMATION; PROTEIN; MICE; NEURODEGENERATION
AB Complement activation is involved in the pathogenesis of age-related macular degeneration. How complement is activated in the retina is not known. Previously we have shown that complement factor H (CFH) is constitutively expressed by retinal pigment epithelial (RPE) cells and the production of CFH is negatively regulated by inflammatory cytokines and oxidative insults. Here we investigated the production and regulation of complement factor B (CFB) in RPE cells. Immunohistochemistry showed that CFB is expressed at low levels on the apical portion of the RPE cells in normal physiological conditions. With age, CFB expression increases and extends to the basal part of RPE cells. Confocal microscopy and real-time PCR of RPE cultures indicated that the production of CFB by RPE cells is positively regulated by TNF-alpha, IFN-gamma and long-term (30 days) photoreceptor outer segments treatments. Increased CFB expression in RPE cells in vivo is accompanied by the accumulation of complement C3 and C3a deposition at the Bruch's membrane and the basal layer of RPE cells. Our results suggest that RPE cells play important roles in regulating complement activation in the retina. Increased complement activation in the aged retina may be important for retinal homeostasis in the context of accumulating photoreceptor waste products. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Chen, Mei; Muckersie, Elizabeth; Robertson, Marie; Forrester, John V.; Xu, Heping] Univ Aberdeen, Dept Ophthalmol, Inst Med Sci, Aberdeen AB25 2ZD, Scotland.
C3 University of Aberdeen
RP Xu, HP (通讯作者)，Univ Aberdeen, Dept Ophthalmol, Inst Med Sci, Aberdeen AB25 2ZD, Scotland.
EM hxu@abdn.ac.uk
RI Xu, Heping/A-4430-2008
OI Xu, Heping/0000-0003-4000-931X
FU the American Health Assistance Foundation (AHAF) for Macular
   Degeneration Research; Tenovus Scotland; Department of Trade and
   Industry (DTI); Office of Science and Technology (OST)
FX This project is supported by the American Health Assistance Foundation
   (AHAF) for Macular Degeneration Research and in part by Tenovus
   Scotland. Dr Heping Xu thanks the Department of Trade and Industry (DTI)
   and Office of Science and Technology (OST) for supporting his Research
   Council UK (RCUK) fellowship.
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NR 36
TC 67
Z9 69
U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD DEC
PY 2008
VL 87
IS 6
BP 543
EP 550
DI 10.1016/j.exer.2008.09.005
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 385OQ
UT WOS:000261823900008
PM 18926817
DA 2022-11-30
ER

PT J
AU Greenstein, VC
   Santos, RAV
   Tsang, SH
   Smith, RT
   Barile, GR
   Seiple, W
AF Greenstein, Vivienne C.
   Santos, Rodrigo A. V.
   Tsang, Stephen H.
   Smith, R. Theodore
   Barile, Gaetano R.
   Seiple, William
TI PREFERRED RETINAL LOCUS IN MACULAR DISEASE Characteristics and Clinical
   Implications
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE Preferred retinal location (PRL); microperimetry; fundus
   autofluorescence; Stargardt disease; age-related macular degeneration
ID SCANNING LASER OPHTHALMOSCOPE; FUNDUS AUTOFLUORESCENCE;
   STARGARDT-DISEASE; CENTRAL SCOTOMAS; DEGENERATION; FIXATION; LOCATION;
   FOVEA
AB Purpose: To investigate the location and fixation stability of preferred retinal locations (PRLs) in patients with macular disease, and the relationship among areas of abnormal fundus autofluorescence, the PRL and visual sensitivity.
   Methods: Fifteen patients (15 eyes) were studied. Seven had Stargardt disease, 1 bull's eye maculopathy, 5 age-related macular degeneration, 1 Best disease, and 1 pattern dystrophy. All tested eyes had areas of abnormal fundus autofluorescence. The PRL was evaluated with fundus photography and the Nidek microperimeter. Visual field sensitivity was measured with the Nidek microperimeter.
   Results: Of the 15 eyes, 4 had foveal and 11 had eccentric fixation. Eccentric PRLs were above the atrophic lesion and their stability did not depend on the degree of eccentricity from the fovea. Visual sensitivity was markedly decreased in locations corresponding to hypofluorescent areas. Sensitivity was not decreased in hyperfluorescent areas corresponding to flecks but was decreased if hyperfluorescence was in the form of dense annuli.
   Conclusion: Eccentric PRLs were in the superior retina in regions of normal fundus autofluorescence. Fixation stability was not correlated with the degree of eccentricity from the fovea. To assess the outcomes of treatment trials it is important to use methods that relate retinal morphology to visual function. RETINA 28:1234-1240, 2008
C1 [Greenstein, Vivienne C.; Santos, Rodrigo A. V.; Tsang, Stephen H.; Smith, R. Theodore; Barile, Gaetano R.] Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA.
   [Greenstein, Vivienne C.; Seiple, William] NYU, Dept Ophthalmol, Sch Med, New York, NY 10016 USA.
C3 Columbia University; New York University
RP Greenstein, VC (通讯作者)，Columbia Univ, Dept Ophthalmol, 630 W 165th St, New York, NY 10032 USA.
EM vcg17@columbia.edu
OI smith, theodore/0000-0002-1693-943X; Seiple, William/0000-0002-5750-650X
FU National Eye Institute [EY 02115]; Research to Prevent Blindness, New
   York, NY; Starr Foundation; Foundation Fighting Blindness; NATIONAL EYE
   INSTITUTE [R01EY015520, R01EY018213] Funding Source: NIH RePORTER
FX Supported by a grant from the National Eye Institute EY 02115 Bethesda,
   MD; by unrestricted funds from Research to Prevent Blindness, New York,
   NY; and grants from the Starr Foundation and the Foundation Fighting
   Blindness.
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NR 21
TC 46
Z9 48
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 OCT
PY 2008
VL 28
IS 9
BP 1234
EP 1240
DI 10.1097/IAE.0b013e31817c1b47
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 366IM
UT WOS:000260474200009
PM 18628727
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Chan-Ling, T
   Baxter, L
   Afzal, A
   Sengupta, N
   Caballero, S
   Rosinova, E
   Grant, MB
AF Chan-Ling, T
   Baxter, L
   Afzal, A
   Sengupta, N
   Caballero, S
   Rosinova, E
   Grant, MB
TI Hematopoietic stem cells provide repair functions after laser-induced
   Bruch's membrane rupture model of choroidal neovascularization
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID ADULT BONE-MARROW; PIGMENT EPITHELIAL-CELLS; ENDOTHELIAL-CELLS; S-100
   PROTEIN; MULLER CELLS; DEVELOPING RETINA; PROGENITOR CELLS; CHEMOKINE
   SDF-1; GROWTH-FACTOR; RAT RETINA
AB Vascular repair by adult hematopoietic stem cells (HSCs) is well-appreciated because these cells are known for their plasticity. We have shown that adult HSCs differentiate into endothelial cells and participate in both retinal and choroidal neovascularization. We asked whether HSCs participated in the wounding response by forming astrocytes, retinal pigment epithelia (RPE), macrophages, and pericytes. Lethally irradiated C57BL6/J mice were reconstituted with HSCs from mice homozygous for green fluorescent protein (GFP) and then subjected to laser-induced rupture of Bruch's membrane. After immunohistochemical examination of ocular tissue, GFP(+) astrocytes were observed concentrated along the edge of the laser wound, where they and mural cells closely ensheathed the neovasculature. GFP(+) vascular endothelial cells and macrophages/microglia were also evident. Large irregularly shaped GFP(+) RPE cells constituted similar to 93% of RPE cells adjacent to the edge of the denuded RPE area. in regions farther away from the wound, GFP(+) RPE cells were integrated among the GFP(-) host RPE. Thus, postnatal HSCs can differentiate into cells expressing markers specific to astrocytes, macrophages/microglia, mural cells, or RPE. These studies suggest that HSCs could serve as a therapeutic source for long-term regeneration of injured retina and choroid in diseases such as age-related macular degeneration and retinitis pigmentosa.
C1 Univ Florida, Dept Pharmacol & Therapeut, Gainesville, FL 32610 USA.
   Univ Sydney, Dept Anat & Histol, Sydney, NSW, Australia.
   Univ Sydney, Biomed Res Inst, Sydney, NSW, Australia.
C3 State University System of Florida; University of Florida; University of
   Sydney; University of Sydney
RP Grant, MB (通讯作者)，Univ Florida, Dept Pharmacol & Therapeut, Acad Res Bldg,ARBS-252,1600 SW Archer Rd, Gainesville, FL 32610 USA.
EM grantma@pharmacology.ufl.edu
RI Chan-Ling, Tailoi/X-2718-2019; Chan-Ling, Tailoi/A-2177-2008
OI Chan-Ling, Tailoi/0000-0002-8225-3671; Afzal, Aqeela/0000-0001-6406-2233
FU NEI NIH HHS [R01 EY007739, EY012601, EY007739, R01 EY012601] Funding
   Source: Medline; NATIONAL EYE INSTITUTE [R01EY012601, R01EY007739,
   R29EY007739] Funding Source: NIH RePORTER
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NR 68
TC 65
Z9 77
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD MAR
PY 2006
VL 168
IS 3
BP 1031
EP 1044
DI 10.2353/ajpath.2006.050697
PG 14
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA 017UV
UT WOS:000235719700031
PM 16507916
OA Green Published
DA 2022-11-30
ER

PT J
AU Eklund, K
   Sonn, U
   Dahlin-Ivanoff, S
AF Eklund, K
   Sonn, U
   Dahlin-Ivanoff, S
TI Long-term evaluation of a health education programme for elderly persons
   with visual impairment. A randomized study
SO DISABILITY AND REHABILITATION
LA English
DT Article
AB In order to implement evidence-based practice, a randomized study was set up to evaluate the ADL-based Health Education Programme 'Discovering new ways' for elderly persons with age-related macular degeneration.
   Purpose: To investigate the impact of this program on perceived security in the performance of daily activities 28 months after the intervention.
   Method: Two-hundred and twenty-nine persons randomized to either the Health Education programme or an Individual Intervention Programme participated in the study. At the 28-month follow-up there was a dropout of 98 persons and the results are based on 62 persons participating in the Health Education Programme and 69 persons in the Individual Intervention Programme.
   Results: There were statistically significant differences in perceived security between the groups in 15 out of 28 daily activities. Furthermore, the Health Education Group showed a significant tendency towards an improved level of security while the Individual Intervention Group tended to deteriorate.
   Conclusions: The findings provide strong support for the long-term effect of the programme and for the implementation of evidence-based practice. The study corroborates the effectiveness of the Health Education Programme in enhancing security and hindering a progressive decline in perceived security in daily activities.
C1 Gothenburg Univ, Inst Occupat Therapy & Physiotherapy, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden.
   Gothenburg Univ, Swedish Inst Hlth Sci, Vardal Inst, SE-40530 Gothenburg, Sweden.
C3 University of Gothenburg; University of Gothenburg
RP Eklund, K (通讯作者)，Gothenburg Univ, Inst Occupat Therapy & Physiotherapy, Sahlgrenska Acad, Box 455, SE-40530 Gothenburg, Sweden.
EM kajsa.eklund@fhs.gu.se
RI Dahlin-Ivanoff, Synneve/U-9819-2018
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NR 21
TC 35
Z9 36
U1 0
U2 6
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0963-8288
EI 1464-5165
J9 DISABIL REHABIL
JI Disabil. Rehabil.
PD APR 8
PY 2004
VL 26
IS 7
BP 401
EP 409
DI 10.1080/09638280410001662950
PG 9
WC Rehabilitation
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Rehabilitation
GA 812YU
UT WOS:000220875600003
PM 15204476
DA 2022-11-30
ER

PT J
AU Chen, BY
   Huang, HS
   Tsai, KJ
   Wu, JL
   Chang, YT
   Chang, MC
   Lu, CM
   Yang, SL
   Huang, HS
AF Chen, Bo-Yie
   Huang, Ho-Shin
   Tsai, Kan-Jen
   Wu, Jia-Lain
   Chang, Ya-Ting
   Chang, Ming-Chih
   Lu, Chun-Mei
   Yang, Shih-Liang
   Huang, Hsiang-Shang
TI Protective Effect of a Water-Soluble Carotenoid-Rich Extract of
   Cordyceps militaris against Light-Evoked Functional Vision Deterioration
   in Mice
SO NUTRIENTS
LA English
DT Article
DE Cordyceps militaris; cordyxanthins; water-soluble carotenoids; retinal
   photodamage; photoreceptor; functional vision; visual contrast
   sensitivity function
ID PHOTODEGRADATION; CROCIN
AB Light-evoked retinal photodamage is considered an important factor contributing to functional vision deterioration and can even lead to light maculopathy or dry age-related macular degeneration. Loss of visual acuity (VA) and visual contrast sensitivity function (VCSF) are the major symptoms of retinal degenerative diseases. Cordyceps militaris is a carotenoid-rich Chinese medicinal fungus with antioxidant, anti-inflammatory, and immunomodulatory functions. C. militaris extract is a natural substance, and its bioactive constituents have been shown to confer health benefits, but their application in retinal tissue and functional vision protection in vivo remain incompletely understood. In the present study, we evaluated the influence of water-soluble, carotenoid-rich C. militaris extracts on the visual performance of light-damaged mouse retinas in vivo, using adult female CD-1 (R) (ICR) albino mice. We showed that oral administration of this C. militaris extract (10 mg/kg, twice daily) protected the neural retina tissue against light-evoked photoreceptor cell death, reduced Muller cell hypertrophic gliosis, and elevated GSH levels and promoted the recovery of VA- and VCSF-thresholds, especially for high spatial frequency-characterized vision. These results suggest that, probably because of its water-soluble carotenoids, C. militaris extract has the potential to prevent or treat light-induced visual dysfunction.
C1 [Chen, Bo-Yie; Wu, Jia-Lain; Chang, Ya-Ting] Chung Shan Med Univ, Dept Optometry, Taichung 40201, Taiwan.
   [Chen, Bo-Yie] Chung Shan Med Univ Hosp, Dept Ophthalmol, Taichung 40201, Taiwan.
   [Huang, Ho-Shin; Lu, Chun-Mei] Bioray Biotech Co Ltd, Dept Res & Dev, Pingtung 90846, Taiwan.
   [Tsai, Kan-Jen] Chung Shan Med Univ, Dept Med Lab & Biotechnol, Taichung 40201, Taiwan.
   [Chang, Ming-Chih] Jen Ai Hosp, Dept Med Educ & Res, Taichung 41625, Taiwan.
   [Yang, Shih-Liang] Natl Taiwan Univ Sport, Dept Exercise Hlth Sci, Taichung 40404, Taiwan.
   [Yang, Shih-Liang] Taichung Hosp, Dept Chinese Med, Minist Hlth & Welf, Taichung 40343, Taiwan.
   [Huang, Hsiang-Shang] Jen Ai Hosp, Dept Cardiol, Taichung 41625, Taiwan.
C3 Chung Shan Medical University; Chung Shan Medical University; Chung Shan
   Medical University Hospital; Chung Shan Medical University; National
   Taiwan University of Sport
RP Yang, SL (通讯作者)，Natl Taiwan Univ Sport, Dept Exercise Hlth Sci, Taichung 40404, Taiwan.; Yang, SL (通讯作者)，Taichung Hosp, Dept Chinese Med, Minist Hlth & Welf, Taichung 40343, Taiwan.; Huang, HS (通讯作者)，Jen Ai Hosp, Dept Cardiol, Taichung 41625, Taiwan.
EM boychen@csmu.edu.tw; adinol.huang@gmail.com; kjt@csmu.edu.tw;
   gloriawu7@gmail.com; tinya0821@gmail.com; zon681123@gmail.com;
   cmlu@bio-ray.com.tw; ysl451ysl@yahoo.com.tw; hsiangshang6206@gmail.com
FU Chung Shan Medical University, Taiwan [CSMU-JAH-105-03]; Ministry of
   Science and Technology, Taiwan [MOST 107-2320-B-040-003-MY2]; Pingtung
   Agricultural Biotechnology Park, Pingtung, Taiwan [110-Agricultural
   Biotechnology-1.6.3-Pingtung-f1]; Jen Ai Hospital, Taiwan
   [CSMU-JAH-105-03]
FX This research was funded by Chung Shan Medical University and Jen Ai
   Hospital, Taiwan, grant number CSMU-JAH-105-03 (H.-S.H. (Hsiang-Shang
   Huang), and K.-J.T.), the Ministry of Science and Technology, Taiwan,
   grant number MOST 107-2320-B-040-003-MY2 (B.-Y.C.), and Pingtung
   Agricultural Biotechnology Park, Pingtung, Taiwan, grant number
   110-Agricultural Biotechnology-1.6.3-Pingtung-f1 (C.-M.L.).
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NR 39
TC 1
Z9 1
U1 8
U2 9
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2072-6643
J9 NUTRIENTS
JI Nutrients
PD APR
PY 2022
VL 14
IS 8
AR 1675
DI 10.3390/nu14081675
PG 12
WC Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Nutrition & Dietetics
GA 0R0QM
UT WOS:000785311200001
PM 35458237
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Xu, MH
   Fan, RY
   Fan, XE
   Shao, Y
   Li, XR
AF Xu, Manhong
   Fan, Ruiyan
   Fan, Xiaoe
   Shao, Yan
   Li, Xiaorong
TI Progress and Challenges of Anti-VEGF Agents and Their Sustained-Release
   Strategies for Retinal Angiogenesis
SO DRUG DESIGN DEVELOPMENT AND THERAPY
LA English
DT Review
DE anti-vascular endothelial growth factor; retinal angiogenesis; anti-VEGF
   drugs; sustained-release strategies; ranibizumab; bevacizumab
ID PIGMENT EPITHELIUM TEARS; DRUG-DELIVERY; INTRAVITREAL INJECTION; MACULAR
   DEGENERATION; POSTERIOR SEGMENT; PLGA NANOPARTICLES; BEVACIZUMAB
   AVASTIN(R); INHIBITS ANGIOGENESIS; OCULAR DELIVERY; NATURAL-HISTORY
AB Currently, the treatment for ocular neovascular diseases, including diabetic macular edema (DME) and age-related macular degeneration (AMD), mainly involves repeated intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs. Although it can preserve vision, repeated injections are an invasive treatment modality, leading to serious complications and reducing patient adherence to treatment. To reduce the frequency of administration, prolong the time of drug action, and avoid repeated intravitreal injections, the combination of sustained-release materials with anti-VEGF drug therapy has become an emphasis in ophthalmology. In this review, we highlight the current state of anti-VEGF technology, its challenges, and the sustained-release strategies under investigation or being used in clinical practice. Both continuous release and considerable therapeutic effects can be achieved by encapsulating anti-VEGF drugs in sustained-release materials to minimize the number of intravitreal injections. At present, two sustained-release materials are being tested in clinical research, and although basic research shows the strong therapeutic application prospects of extended-release drugs, its challenges mainly involve the discrepancy between the release rates in vitro and the efficiency of the drugs in vivo. Briefly, sustained release of anti-VEGF agents is an advantageous strategy for treating retinal angiogenesis.
C1 [Xu, Manhong; Fan, Ruiyan; Shao, Yan; Li, Xiaorong] Tianjin Med Univ, Eye Hosp, Sch Optometry, Tianjin, Peoples R China.
   [Xu, Manhong; Fan, Ruiyan; Shao, Yan; Li, Xiaorong] Tianjin Med Univ, Eye Inst, Natl Clin Res Ctr Ocular Dis, Eye Hosp,Tianjin Key Lab Retinal Funct & Dis,Tianj, Tianjin, Peoples R China.
   [Fan, Xiaoe] Jincheng Peoples Hosp, Dept Ophthalmol, Jincheng, Peoples R China.
   [Shao, Yan; Li, Xiaorong] 251 Fukang Rd, Tianjin 300384, Peoples R China.
C3 Tianjin Medical University; Tianjin Medical University
RP Shao, Y; Li, XR (通讯作者)，251 Fukang Rd, Tianjin 300384, Peoples R China.
EM sytmueh@163.com; xiaorli@163.com
FU National Natural Science Foundation of China [82171085]; Tianjin
   Research Innovation Project for Postgraduate Students [2021YJSB271];
   Natural Science Foundation of Tianjin [19JCZDJC64000]
FX The authors thank Prof.Xiaomin Zhang and Ms.Xuezhi Liang for providing
   us the authoring environment, space and time for this review article.
   This work is supported by the National Natural Science Foundation of
   China (82171085) , Tianjin Research Innovation Project for Postgraduate
   Students (2021YJSB271) and Natural Science Foundation of Tianjin
   (19JCZDJC64000) .
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NR 147
TC 0
Z9 0
U1 2
U2 2
PU DOVE MEDICAL PRESS LTD
PI ALBANY
PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND
SN 1177-8881
J9 DRUG DES DEV THER
JI Drug Des. Dev. Ther.
PY 2022
VL 16
BP 3241
EP 3262
DI 10.2147/DDDT.S383101
PG 22
WC Chemistry, Medicinal; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA 4Y4RW
UT WOS:000861516000001
PM 36172053
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Arora, S
   Surakiatchanukul, T
   Arora, T
   Errera, MH
   Agrawal, H
   Lupidi, M
   Chhablani, J
AF Arora, Supriya
   Surakiatchanukul, Thamolwan
   Arora, Tarun
   Errera, Marie Helene
   Agrawal, Hitesh
   Lupidi, Marco
   Chhablani, Jay
TI Retinal toxicities of systemic anticancer drugs
SO SURVEY OF OPHTHALMOLOGY
LA English
DT Review
DE Drug toxicity; targeted agents; conventional chemotherapy; retinal
   toxicity; ocular adverse effects; anticancer drugs; MEK inhibitors; BRAF
   inhibitors; immunotherapy
ID CHRONIC HEPATITIS-C; INTERFERON-ALPHA THERAPY; CENTRAL-NERVOUS-SYSTEM;
   CYSTOID MACULAR EDEMA; RIBAVIRIN COMBINATION THERAPY; CISPLATIN-BASED
   CHEMOTHERAPY; ALBUMIN-BOUND PACLITAXEL; SUPRAOPHTHALMIC CAROTID
   INFUSION; INHIBITOR-ASSOCIATED RETINOPATHY; PEMBROLIZUMAB-INDUCED
   UVEITIS
AB Newer anticancer drugs have revolutionized cancer treatment in the last decade, but conventional chemotherapy still occupies a central position in many cancers, with combination therapy and newer methods of delivery increasing their efficacy while minimizing toxicities. We discuss the retinal toxicities of anticancer drugs with an emphasis on the mechanism of toxicity. Uveitis is seen with the use of v-raf murine sarcoma viral oncogene homolog B editing anticancer inhibitors as well as immunotherapy. Most of the cases are mild with only anterior uveitis, but severe cases of posterior uveitis, panuveitis, and Vogt-KoyanagiHarada-like disease may also occur. In the retina, a transient neurosensory detachment is observed in almost all patients on mitogen-activated protein kinase kinase (MEK) inhibitors. Microvasculopathy is often seen with interferon alpha, but vascular occlusion is a more serious toxicity caused by interferon alpha and MEK inhibitors. Crystalline retinopathy with or without macular edema may occur with tamoxifen; however, even asymptomatic patients may develop cavitatory spaces seen on optical coherence tomography. A unique macular edema with angiographic silence is characteristic of taxanes. Delayed dark adaptation has been observed with fenretinide. Interestingly, this drug is finding potential application in Stargardt disease and age-related macular degeneration. (c) 2021 Elsevier Inc. All rights reserved..
C1 [Arora, Supriya; Arora, Tarun] Bahamas Vis Ctr, Nassau, New Providence, Bahamas.
   [Arora, Supriya; Arora, Tarun] Princess Margaret Hosp, Nassau, New Providence, Bahamas.
   [Surakiatchanukul, Thamolwan] Jamaica Hosp Med Ctr, New York Med Coll, Jamaica, NY USA.
   [Arora, Tarun] Princess Margaret Hosp, Eye Care Ctr, Nassau, New Providence, Bahamas.
   [Errera, Marie Helene] Univ Pittsburgh, Dept Ophthalmol, UPMC Eye Ctr, Pittsburgh, PA 15260 USA.
   [Agrawal, Hitesh] LV Prasad Eye Inst, Uveitis & Ocular Immunol Serv, Hyderabad, India.
   [Lupidi, Marco] Univ Perugia, Dept Biochem & Surg Sci, Sect Ophthalmol, Perugia, Italy.
   [Chhablani, Jay] Univ Pittsburgh, UPMC Eye Ctr, Pittsburgh, PA USA.
C3 New York Medical College; Pennsylvania Commonwealth System of Higher
   Education (PCSHE); University of Pittsburgh; L. V. Prasad Eye Institute;
   University of Perugia; Pennsylvania Commonwealth System of Higher
   Education (PCSHE); University of Pittsburgh
RP Chhablani, J (通讯作者)，Univ Pittsburgh, UPMC Eye Ctr, Dept Ophthalmol, Pittsburgh, PA 15213 USA.
EM supriyaaroragnce@gmail.com; draroratarun@gmail.com;
   jay.chhablani@gmail.com
OI Paez-Escamilla, Manuel/0000-0003-3488-9680; Lupidi,
   Marco/0000-0002-6817-2488
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NR 507
TC 4
Z9 4
U1 2
U2 6
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 JAN-FEB
PY 2022
VL 67
IS 1
BP 97
EP 148
DI 10.1016/j.survophthal.2021.05.007
EA DEC 2021
PG 52
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA XT2FE
UT WOS:000733409100010
PM 34048859
DA 2022-11-30
ER

PT J
AU Ambati, M
   Apicella, I
   Wang, SB
   Narendran, S
   Leung, H
   Pereira, F
   Nagasaka, Y
   Huang, P
   Varshney, A
   Baker, KL
   Marion, KM
   Shadmehr, M
   Stains, CI
   Werner, BC
   Sadda, SR
   Taylor, EW
   Sutton, SS
   Magagnoli, J
   Gelfand, BD
AF Ambati, Meenakshi
   Apicella, Ivana
   Wang, Shao-bin
   Narendran, Siddharth
   Leung, Hannah
   Pereira, Felipe
   Nagasaka, Yosuke
   Huang, Peirong
   Varshney, Akhil
   Baker, Kirstie L.
   Marion, Kenneth M.
   Shadmehr, Mehrdad
   Stains, Cliff, I
   Werner, Brian C.
   Sadda, Srinivas R.
   Taylor, Ethan W.
   Sutton, S. Scott
   Magagnoli, Joseph
   Gelfand, Bradley D.
TI Identification of fluoxetine as a direct NLRP3 inhibitor to treat
   atrophic macular degeneration
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE fluoxetine; macular degeneration; retina; health insurance databases;
   molecular modeling
ID INFLAMMASOME ACTIVATION; METAANALYSIS; BINDING; PROTEIN; TOXINS; BRAIN;
   RNA
AB The atrophic form of age-related macular degeneration (dry AMD) affects nearly 200 million people worldwide. There is no Food and Drug Administration (FDA)-approved therapy for this disease, which is the leading cause of irreversible blindness among people over 50 y of age. Vision loss in dry AMD results from degeneration of the retinal pigmented epithelium (RPE). RPE cell death is driven in part by accumulation of Alu RNAs, which are noncoding transcripts of a human retrotransposon. Alu RNA induces RPE degeneration by activating the NLRP3-ASC inflammasome. We report that fluoxetine, an FDA-approved drug for treating clinical depression, binds NLRP3 in silico, in vitro, and in vivo and inhibits activation of the NLRP3-ASC inflammasome and inflammatory cytokine release in RPE cells and macrophages, two critical cell types in dry AMD. We also dem-onstrate that fluoxetine, unlike several other antidepressant drugs, reduces Alu RNA-induced RPE degeneration in mice. Finally, by an-alyzing two health insurance databases comprising more than 100 million Americans, we report a reduced hazard of developing dry AMD among patients with depression who were treated with flu-oxetine. Collectively, these studies identify fluoxetine as a potential drug-repurposing candidate for dry AMD.
C1 [Ambati, Meenakshi; Apicella, Ivana; Wang, Shao-bin; Narendran, Siddharth; Leung, Hannah; Pereira, Felipe; Nagasaka, Yosuke; Huang, Peirong; Varshney, Akhil; Gelfand, Bradley D.] Univ Virginia, Sch Med, Ctr Adv Vis Sci, Charlottesville, VA 22901 USA.
   [Ambati, Meenakshi; Apicella, Ivana; Wang, Shao-bin; Narendran, Siddharth; Leung, Hannah; Pereira, Felipe; Nagasaka, Yosuke; Huang, Peirong; Varshney, Akhil; Gelfand, Bradley D.] Univ Virginia, Dept Ophthalmol, Sch Med, Charlottesville, VA 22908 USA.
   [Ambati, Meenakshi] Ctr Digital Image Evaluat, Charlottesville, VA 22901 USA.
   [Narendran, Siddharth] Aravind Eye Hosp Syst, Madurai 625020, Tamil Nadu, India.
   [Pereira, Felipe] Univ Fed Sao Paulo, Escola Paulista Med, Dept Oftalmol & Ciencias Visuais, BR-04023062 Sao Paulo, Brazil.
   [Baker, Kirstie L.; Marion, Kenneth M.; Sadda, Srinivas R.] Doheny Eye Inst, Los Angeles, CA 90033 USA.
   [Shadmehr, Mehrdad; Stains, Cliff, I] Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA.
   [Stains, Cliff, I] Univ Virginia, Canc Ctr, Charlottesville, VA 22908 USA.
   [Werner, Brian C.] Univ Virginia, Sch Med, Dept Orthopaed Surg, Charlottesville, VA 22908 USA.
   [Sadda, Srinivas R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
   [Taylor, Ethan W.] Univ N Carolina, Dept Chem & Biochem, Greensboro, NC 27412 USA.
   [Sutton, S. Scott; Magagnoli, Joseph] Univ South Carolina, Coll Pharm, Dept Clin Pharm & Outcomes Sci, Columbia, SC 29208 USA.
   [Gelfand, Bradley D.] Univ Virginia, Sch Med, Dept Biomed Engn, Charlottesville, VA 22908 USA.
   [Varshney, Akhil] Dr Shroffs Char Eye Hosp, 5027 Daryaganj, New Delhi, India.
C3 University of Virginia; University of Virginia; Universidade Federal de
   Sao Paulo (UNIFESP); Doheny Eye Institute; University of Virginia;
   University of Virginia; University of Virginia; 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 North Carolina; University of North Carolina Greensboro;
   University of South Carolina System; University of South Carolina
   Columbia; University of Virginia
RP Gelfand, BD (通讯作者)，Univ Virginia, Sch Med, Ctr Adv Vis Sci, Charlottesville, VA 22901 USA.; Gelfand, BD (通讯作者)，Univ Virginia, Dept Ophthalmol, Sch Med, Charlottesville, VA 22908 USA.; Magagnoli, J (通讯作者)，Univ South Carolina, Coll Pharm, Dept Clin Pharm & Outcomes Sci, Columbia, SC 29208 USA.; Gelfand, BD (通讯作者)，Univ Virginia, Sch Med, Dept Biomed Engn, Charlottesville, VA 22908 USA.
EM bcw4x@hscmail.mcc.virginia.edu; magagnol@mailbox.sc.edu;
   gelfand@virginia.edu
RI WANG, SHAO-BIN/Z-1810-2018
OI WANG, SHAO-BIN/0000-0002-6699-9406; PEREIRA, FELIPE/0000-0001-8884-2816
FU University of Virginia Strategic Investment Fund; NIH [R01EY028027,
   R01EY031039, R01EY032512, R35GM119751]; BrightFocus Foundation; Owens
   Family Foundation; University of Virginia; FP7 WeNMR European
   e-Infrastructure project [261572]; H2020 West-Life European
   e-Infrastructure project [675858]; European Open Science Cloud Hub
   European e-Infrastructure project [777536]; national Grid Initiative of
   Belgium; national Grid Initiative of France; national Grid Initiative of
   Italy; national Grid Initiative of Germany; national Grid Initiative of
   the Netherlands; national Grid Initiative of Poland; national Grid
   Initiative of Portugal; national Grid Initiative of Spain; national Grid
   Initiative of United Kingdom; national Grid Initiative of Taiwan; US
   Open Science Grid
FX We thank D. Robertson, G. Pattison, J. Hu, and K.A. Fox for their
   technical assistance. This work was funded, in part, by the University
   of Virginia Strategic Investment Fund. B.D.G. has received support from
   NIH grants (R01EY028027, R01EY031039, and R01EY032512), BrightFocus
   Foundation, and the Owens Family Foundation. C.I.S. received support
   from the NIH (R35GM119751) and the University of Virginia. The FP7 WeNMR
   (Project No. 261572), H2020 West-Life (Project No. 675858), and the
   European Open Science Cloud Hub (Project No. 777536) European
   e-Infrastructure projects are acknowledged for the use of their web
   portals, which make use of the European Grid Infrastructure with the
   dedicated support of CESNETMetaCloud, Italian Institute of Nuclear
   Physics Padova, NCG-INGRID-PT, Taiwan National Center for
   High-performance Computing, SURFsara, and Dutch National Institute for
   Subatomic Physics and the additional support of the national Grid
   Initiatives of Belgium, France, Italy, Germany, the Netherlands, Poland,
   Portugal, Spain, United Kingdom, Taiwan, and the US Open Science Grid.
   The content of this article is solely our responsibility and does not
   necessarily represent the official views of the NIH. 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 41
TC 9
Z9 9
U1 2
U2 7
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 OCT 12
PY 2021
VL 118
IS 41
AR e2102975118
DI 10.1073/pnas.2102975118
PG 9
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA WH8UU
UT WOS:000707946400008
PM 34620711
OA Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Taibouni, K
   Miere, A
   Samake, A
   Souied, E
   Petit, E
   Chenoune, Y
AF Taibouni, Kawther
   Miere, Alexandra
   Samake, Abdourahmane
   Souied, Eric
   Petit, Eric
   Chenoune, Yasmina
TI Choroidal Neovascularization Screening on OCT-Angiography
   Choriocapillaris Images by Convolutional Neural Networks
SO APPLIED SCIENCES-BASEL
LA English
DT Article
DE age-related macular degeneration; choroidal neovascularization;
   convolutional neural networks; image classification; optical coherence
   tomography angiography
ID MACULAR DEGENERATION
AB Choroidal Neovascularization (CNV) is the advanced stage of Age-related Macular Degeneration (AMD), which is the leading cause of irreversible visual loss for elder people in developed countries. Optical Coherence Tomography Angiography (OCTA) is a recent non-invasive imaging technique widely used nowadays in diagnosis and follow-up of CNV. In this study, an automatic screening of CNV based on deep learning is performed using OCTA choriocapillaris images. CNV eyes (advanced wet AMD) are diagnosed among healthy eyes (no AMD) and eyes with drusen (intermediate AMD). An OCTA dataset of 1396 images is used to train and evaluate the model. A pre-trained convolutional neural network (CNN) is fine-tuned and validated on 80% of the dataset while the remaining 20% is used independently for predictions. The model can accurately detect CNV on the test set with an accuracy of 89.74%, precision of 0.96 and 0.99 area under the curve of the receiver operating characteristic. A good overall classification accuracy of 88.46% is obtained on a balanced test set. Detailed analysis of misclassified images shows that they are also considered ambiguous images for expert clinicians. This novel CNN-based application is truly a breakthrough to assist clinicians in the challenging task of screening for neovascular complications.
C1 [Taibouni, Kawther; Samake, Abdourahmane; Petit, Eric; Chenoune, Yasmina] Univ Paris Est Creteil, Lab Images Signals & Intelligent Syst LISSI, EA 3956, F-94400 Paris, France.
   [Miere, Alexandra; Souied, Eric] Ctr Hosp Intercommunal Creteil, Dept Ophthalmol, 40 Ave Verdun, F-94010 Paris, France.
   [Chenoune, Yasmina] ESME Sudria Res Lab, 34 Rue Fleurus, F-75006 Paris, France.
C3 Universite Paris-Est-Creteil-Val-de-Marne (UPEC); Universite
   Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil
RP Chenoune, Y (通讯作者)，Univ Paris Est Creteil, Lab Images Signals & Intelligent Syst LISSI, EA 3956, F-94400 Paris, France.; Chenoune, Y (通讯作者)，ESME Sudria Res Lab, 34 Rue Fleurus, F-75006 Paris, France.
EM kawther.taibouni@univ-paris-est.fr; alexandra.miere@chicreteil.fr;
   abdou.samake0908@gmail.com; Eric.Souied@chicreteil.fr; petit@u-pec.fr;
   yasmina.chenoune@esme.fr
RI Chenoune Leroul, Yasmina/GSE-3131-2022; Miere, Alexandra/AIC-4074-2022
OI Chenoune Leroul, Yasmina/0000-0002-8143-4796; Miere,
   Alexandra/0000-0003-4123-8210
CR Abadi M., ARXIV160304467
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NR 35
TC 2
Z9 2
U1 2
U2 13
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2076-3417
J9 APPL SCI-BASEL
JI Appl. Sci.-Basel
PD OCT
PY 2021
VL 11
IS 19
AR 9313
DI 10.3390/app11199313
PG 13
WC Chemistry, Multidisciplinary; Engineering, Multidisciplinary; Materials
   Science, Multidisciplinary; Physics, Applied
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry; Engineering; Materials Science; Physics
GA WH2AD
UT WOS:000707486700001
OA gold
DA 2022-11-30
ER

PT J
AU Zhu, MH
   Wang, Y
   Zhu, LL
   Du, S
   Wang, ZZ
   Zhang, YT
   Guo, Y
   Tu, YY
   Song, E
AF Zhu, Manhui
   Wang, Ying
   Zhu, Linling
   Du, Shu
   Wang, Zhenzhen
   Zhang, Yuting
   Guo, Yang
   Tu, Yuanyuan
   Song, E.
TI Crosstalk Between RPE Cells and Choroidal Endothelial Cells via the
   ANXA1/FPR2/SHP2/NLRP3 Inflammasome/Pyroptosis Axis Promotes Choroidal
   Neovascularization
SO INFLAMMATION
LA English
DT Article
DE Age-related macular degeneration (AMD); Choroidal neovascularization
   (CNV); Retinal pigment epithelial (RPE) cells; Choroidal endothelial
   cells (CECs); Annexin A1 (ANXA1); Nod-like receptor family; pyrin domain
   containing 3 (NLRP3) inflammasome
ID ANNEXIN A1; TRANSCRIPTIONAL REGULATION; MACULAR DEGENERATION; FPR2/ALX
   GENE; GROWTH-FACTOR; RECEPTOR; ANGIOGENESIS; IDENTIFICATION; MIGRATION;
   PROTEIN
AB One type of age-related macular degeneration (AMD), neovascular (nAMD), characterized by choroidal neovascularization (CNV), accounts for the majority of the severe central vision impairment associated with AMD. Endothelial cells (ECs) in direct contact with retinal pigment epithelial (RPE) cells are more prone to the pathological angiogenesis involved in CNV. Herein, we investigated the effect of crosstalk between RPE cells and choroidal endothelial cells (CECs) via the ANXA1/FPR2/NLRP3 inflammasome/pyroptosis axis on the development of choroidal neovascularization (CNV) in vitro and in vivo. ANXA1 expression and secretion from ARPE-19 cells were upregulated by hypoxia. FPR2 expression, especially on the plasma membrane, in HCECs was upregulated under hypoxic conditions. ANXA1 secreted from ARPE-19 cells inhibited NLRP3 inflammasome activation and NLRP3 inflammasome-mediated pyroptosis in HCECs by activating the FPR2/SHP2 axis. Moreover, ANXA1 secreted by ARPE-19 cells promoted behaviors of HCECs, including proliferation, migration, and tube formation, by activating the FPR2/SHP2 axis and inhibiting NLRP3 inflammasome-mediated pyroptosis. Inhibiting the upregulated ANXA1/FPR2/SHP2/NLRP3 inflammasome/pyroptosis axis decreased the volume of CNV. Our data suggest that the crosstalk between RPE cells and CECs via the ANXA1/FPR2/NLRP3 inflammasome/pyroptosis axis promotes CNV. This finding could identify a potential target for the prevention and treatment of CNV.
C1 [Zhu, Manhui; Wang, Ying; Zhu, Linling; Du, Shu; Wang, Zhenzhen; Zhang, Yuting; Guo, Yang; Tu, Yuanyuan; Song, E.] Soochow Univ, Lixiang Eye Hosp, Dept Ophthalmol, Suzhou, Jiangsu, Peoples R China.
   [Wang, Ying] Nanjing Med Univ, Affiliated Suzhou Hosp, Suzhou Municipal Hosp, Dept Ophthalmol, Suzhou, Jiangsu, Peoples R China.
C3 Soochow University - China; Nanjing Medical University
RP Tu, YY; Song, E (通讯作者)，Soochow Univ, Lixiang Eye Hosp, Dept Ophthalmol, Suzhou, Jiangsu, Peoples R China.
EM tuyuanyuaneye@163.com; songe@suda.edu.cn
RI 涂, 园园/AGE-3991-2022
OI Song, E/0000-0003-4259-9739
FU Suzhou Science and Technology Bureau [SYS2018005]; National Natural
   Science Foundation of China [81770906]; Jiangsu Provincial Natural
   Science Foundation Project [BK20200209, BK20191177]; Suzhou Commission
   of Health and Family Planning [KJXW2018076]; Project of Suzhou Lixiang
   Eye Hospital [SLKY2020120]
FX The study was supported by the Suzhou Science and Technology Bureau (No.
   SYS2018005), the National Natural Science Foundation of China (No.
   81770906), the Jiangsu Provincial Natural Science Foundation Project
   (Nos. BK20200209 and BK BK20191177), the Suzhou Commission of Health and
   Family Planning (No. KJXW2018076), and the Project of Suzhou Lixiang Eye
   Hospital (No. SLKY2020120).
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NR 39
TC 2
Z9 2
U1 1
U2 7
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0360-3997
EI 1573-2576
J9 INFLAMMATION
JI Inflammation
PD FEB
PY 2022
VL 45
IS 1
BP 414
EP 427
DI 10.1007/s10753-021-01555-3
EA OCT 2021
PG 14
WC Cell Biology; Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Immunology
GA YP9WY
UT WOS:000702229600001
PM 34595678
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Campochiaro, PA
   Akhlaq, A
AF Campochiaro, Peter A.
   Akhlaq, Anam
TI Sustained suppression of VEGF for treatment of retinal/choroidal
   vascular diseases
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Review
DE Age-related macular degeneration; Diabetic retinopathy; Retinal vein
   occlusion; Microparticles; Gene transfer
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL VEIN OCCLUSION; DIABETIC MACULAR
   EDEMA; EPITHELIUM-DERIVED FACTOR; BEVACIZUMAB AVASTIN THERAPY;
   PRO-PERMEABILITY FACTORS; FACTOR-H POLYMORPHISM; LONG-TERM OUTCOMES;
   CHOROIDAL NEOVASCULARIZATION; RETINOPATHY SEVERITY
AB Neovascular age-related macular degeneration (NVAMD) is the most prevalent choroidal vascular disease, and diabetic retinopathy (DR) and retinal vein occlusion (RVO) are the most prevalent retinal vascular diseases. In each of these, hypoxia plays a central role by stabilizing hypoxia-inducible factor-1 which increases production of vascular endothelial growth factor (VEGF) and other hypoxia-regulated gene products. High VEGF causes excessive vascular permeability, neovascularization, and in DR and RVO, promotes closure of retinal vessels exacerbating hypoxia and creating a positive feedback loop. Hence once VEGF expression is elevated it tends to remain elevated and drives disease progression. While other hypoxia-regulated gene products also contribute to pathology in these disease processes, it is remarkable how much pathology is reversed by selective inhibition of VEGF. Clinical trials have demonstrated outstanding visual outcomes in patients with NVAMD, DR, or RVO from frequent intraocular injections of VEGF-neutralizing proteins, but for a variety of reasons injection frequency has been substantially less in clinical practice and visual outcomes are disappointing. Herein we discuss the rationale, preclinical, and early clinical results of new approaches that provide sustained suppression of VEGF. These approaches will revolutionize the management of these prevalent retinal/choroidal vascular diseases.
C1 [Campochiaro, Peter A.; Akhlaq, Anam] Johns Hopkins Univ, Sch Med, Dept Ophthalmol & Neurosci, Baltimore, MD USA.
C3 Johns Hopkins University
RP Campochiaro, PA (通讯作者)，Johns Hopkins Univ Hosp, Wilmer Eye Inst, 815 Maumenee,600 N Wolfe St, Baltimore, MD 21287 USA.
EM pcampo@jhmi.edu
OI Campochiaro, Peter/0000-0003-2531-8229
FU ALLEGRO; SANOFI GENZYME; GRAYBUG VISION; MERCK CO, INC.; PERFUSE;
   REGENERON PHARMACEUTICALS, INC.; REGENXBIO, INC.; WAVE LIFE SCIENCES
FX PAC:AERPIO PHARMACEUTICALS: Advisory Board, Honoraria to JHU,
   Investigator, Grant; ALLEGRO: Advisory Board, Equity; APPLIED GENETIC
   TECHNOLOGIES CORPORATION: Advisory Board, Honoraria; ASCLEPIX
   THERAPEUTICS: Consultant, Honoraria; ASHVATTHA THERAPEUTICS: Consultant,
   Honoraria; BAUCSH and LOMB: Consultant, Honoraria; CLEARSIDE:
   Consultant; CUREVAC: Consultant, Honoraria; EXONATE LTD: Advisory Board,
   Honoraria GENENTECH/ROCHE INC: Advisory Board, Honoraria to JHU,
   Investigator, Grants; SANOFI GENZYME: Investigator, Grant; GRAYBUG
   VISION: Consultant, Honoraria, CoFounder, Equity, Grant; MERCK & CO,
   INC: Advisory Board, Honoraria; OXFORD BIOMEDICA: Investigator, Grant;
   PERFUSE; REGENERON PHARMACEUTICALS, INC: Investigator, Grant; REGENXBIO,
   INC: Investigator, Grant; WAVE LIFE SCIENCES: Consultant, Honoraria.
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NR 153
TC 37
Z9 37
U1 16
U2 22
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1350-9462
EI 1873-1635
J9 PROG RETIN EYE RES
JI Prog. Retin. Eye Res.
PD JUL
PY 2021
VL 83
AR 100921
DI 10.1016/j.preteyeres.2020.100921
EA JUL 2021
PG 15
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA TM9WL
UT WOS:000675896900002
PM 33248215
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Qassim, A
   Souzeau, E
   Hollitt, G
   Hassall, MM
   Siggs, OM
   Craig, JE
AF Qassim, Ayub
   Souzeau, Emmanuelle
   Hollitt, Georgie
   Hassall, Mark M.
   Siggs, Owen M.
   Craig, Jamie E.
TI Risk Stratification and Clinical Utility of Polygenic Risk Scores in
   Ophthalmology
SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
LA English
DT Review
DE polygenic risk scores; risk prediction; common complex disease; GWAS
ID OPEN-ANGLE GLAUCOMA; GENOME-WIDE ASSOCIATION; MACULAR DEGENERATION;
   GENETIC RISK; INTRAOCULAR-PRESSURE; REFRACTIVE ERROR; PROGRESSION;
   MYOPIA; SUSCEPTIBILITY; PREDICTION
AB Combining genetic and clinical data into an informative risk prediction profile has been an important ambition of personalized medicine. Single-nucleotide polymorphisms are commonly found throughout the genome and account for the majority of interindividual genetic variation. To date, genome-wide association studies have led to the discovery of thousands of disease-associated loci, including across dozens of ophthalmic diseases and traits. However, compared with the clinical utility of identifying rare Mendelian variants, the translation of these results to clinical practice has so far been limited because such variants are found commonly in the population, and individually account for a very small risk. Recently, combining large numbers of these genetic variants into polygenic risk scores (PRS) has shown clinically meaningful risk prediction across several common diseases. PRS have the potential to translate the discovery of common risk variants into individualized disease risk prediction, prognostication, and may enable targeted treatments. In this context, we review the clinical utility of PRS in three common, genetically complex ophthalmic conditions: primary open angle glaucoma, age-related macular degeneration, and myopia.
   Translational Relevance: Common genetic variants can be used to effectively stratify the risk of disease development and progression and may be used to guide screening, triaging, monitoring, or treatment thresholds.
C1 [Qassim, Ayub; Souzeau, Emmanuelle; Hollitt, Georgie; Hassall, Mark M.; Siggs, Owen M.; Craig, Jamie E.] Flinders Univ S Australia, Flinders Med Ctr, Dept Ophthalmol, Bedford Pk, SA, Australia.
C3 Flinders Medical Centre; Flinders University South Australia
RP Qassim, A (通讯作者)，Flinders Univ S Australia, Dept Ophthalmol, Level 2 Car Pk Tenancies,1 Flinders Dr, Bedford Pk, SA 5042, Australia.
EM ayub.qassim@flinders.edu.au
RI Souzeau, Emmanuelle/AAB-5608-2022
OI Souzeau, Emmanuelle/0000-0002-2015-6577; Siggs,
   Owen/0000-0003-2840-4851; Hollitt, Georgie/0000-0003-1113-6109; Craig,
   Jamie/0000-0001-9955-9696; Hassall, Mark M./0000-0002-6180-7954; Qassim,
   Ayub/0000-0002-2911-2941
FU National Health and Medical Research Council (NHMRC) [APP1150144,
   APP1157571]; fulltime Avant Doctor in Training scholarship
FX Supported by the National Health and Medical Research Council (NHMRC
   Program Grant APP1150144 and Project Grant APP1157571) . AQ was funded
   by a fulltime Avant Doctor in Training scholarship. JEC was an NHMRC
   Practitioner Fellow.
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NR 97
TC 5
Z9 5
U1 2
U2 7
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 2021
VL 10
IS 6
AR 14
DI 10.1167/tvst.10.6.14
PG 14
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA SL4VP
UT WOS:000656917500008
PM 34111261
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Higgins, BE
   Montesano, G
   Binns, AM
   Crabb, DP
AF Higgins, Bethany E.
   Montesano, Giovanni
   Binns, Alison M.
   Crabb, David P.
TI Optimising assessment of dark adaptation data using time to event
   analysis
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MACULAR DEGENERATION; NATURAL-HISTORY; ROD; CONE
AB In age-related macular degeneration (AMD) research, dark adaptation has been found to be a promising functional measurement. In more severe cases of AMD, dark adaptation cannot always be recorded within a maximum allowed time for the test (similar to 20-30 min). These data are recorded either as censored data-points (data capped at the maximum test time) or as an estimated recovery time based on the trend observed from the data recorded within the maximum recording time. Therefore, dark adaptation data can have unusual attributes that may not be handled by standard statistical techniques. Here we show time-to-event analysis is a more powerful method for analysis of rod-intercept time data in measuring dark adaptation. For example, at 80% power (at alpha=0.05) sample sizes were estimated to be 20 and 61 with uncapped (uncensored) and capped (censored) data using a standard t-test; these values improved to 12 and 38 when using the proposed time-to-event analysis. Our method can accommodate both skewed data and censored data points and offers the advantage of significantly reducing sample sizes when planning studies where this functional test is an outcome measure. The latter is important because designing trials and studies more efficiently equates to newer treatments likely being examined more efficiently.
C1 [Higgins, Bethany E.; Montesano, Giovanni; Binns, Alison M.; Crabb, David P.] City Univ London, Sch Hlth Sci, Optometry & Visual Sci, Northampton Sq, London EC1V 0HB, England.
   [Montesano, Giovanni] Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr, Moorfields Eye Hosp, London, England.
   [Montesano, Giovanni] UCL Inst Ophthalmol, London, England.
C3 City University London; University of London; University College London;
   Moorfields Eye Hospital NHS Foundation Trust; University of London;
   University College London
RP Crabb, DP (通讯作者)，City Univ London, Sch Hlth Sci, Optometry & Visual Sci, Northampton Sq, London EC1V 0HB, England.
EM david.crabb.1@city.ac.uk
OI Crabb, David/0000-0001-8754-3902; Higgins, Bethany/0000-0002-4530-6156;
   Binns, Alison/0000-0001-8621-498X
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NR 33
TC 2
Z9 2
U1 0
U2 2
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD APR 15
PY 2021
VL 11
IS 1
AR 8323
DI 10.1038/s41598-021-86193-3
PG 10
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA RP6NY
UT WOS:000641844600079
PM 33859209
OA Green Accepted, Green Published, gold
DA 2022-11-30
ER

PT J
AU Song, QT
   Zhao, Y
   Yang, YR
   Han, X
   Duan, JG
AF Song, Qiongtao
   Zhao, Ying
   Yang, Yanrong
   Han, Xue
   Duan, Junguo
TI Astragaloside IV protects against retinal iron overload toxicity through
   iron regulation and the inhibition of MAPKs and NF-kappa B activation
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Astragaloside IV; Iron overload; Reactive oxygen species; Inflammation;
   Apoptosis; Iron-handling protein
ID CHELATOR DEFERIPRONE PROTECTS; PIGMENT EPITHELIUM; HEPATIC-FIBROSIS;
   CELLS; DEGENERATION; EXPRESSION; MITOCHONDRIA; KINASE
AB Iron overload toxicity has been implicated in retinal pigment epithelial cell injury in age-related macular degeneration. This study investigates the effects of astragaloside IV (AS-IV), a potential retinal protective agent, on the toxicity process of retinal iron overload in vivo and in vitro. AS-IV partially restored the retinal expression of rhodopsin and retinal pigment epithelium-specific 65 kDa protein, suppressed oxidative stress and inflammatory markers, and alleviated iron deposition and retinal pathological changes in vivo. Also, AS-IV inhibited the phosphorylation of p38 and ERK mitogen-activated protein kinases (MAPKs), as well as the nuclear translocation of nuclear factor-kappa B (NF-kappa B). Furthermore, AS-IV prevented cell death by decreasing the ratio of Bax/Bcl-2, caspase-3, and cleaved caspase-3 expression in vitro. Although there are no chelation effects between AS-IV and iron, AS-IV can reduce intracellular iron by regulating iron-handling proteins in ARPE-1 9 cells (Cav1.2, divalent metal transporter-1, transferrin receptor 1, and heavy-chain ferritin). In conclusion, the results show that AS-IV has significant protective effects against retinal iron overload toxicity and suggest that iron regulation and the inhibition of MAPKs and NF-kappa B activation might be mechanisms underlying the effects of AS-IV.
C1 [Song, Qiongtao; Zhao, Ying; Yang, Yanrong; Duan, Junguo] Chengdu Univ TCM, Eye Sch, 37 Twelve Bridge Rd, Chengdu 610075, Sichuan, Peoples R China.
   [Song, Qiongtao; Zhao, Ying; Yang, Yanrong; Duan, Junguo] Chengdu Univ TCM, Ineye Hosp, 8 Xinghui Rd, Chengdu 610084, Sichuan, Peoples R China.
   [Song, Qiongtao; Zhao, Ying; Yang, Yanrong; Duan, Junguo] Key Lab Sichuan Prov Ophthalmopathy Prevent & Cur, 37 Twelve Bridge Rd, Chengdu 610075, Sichuan, Peoples R China.
   [Han, Xue] Hebei Key Lab Integrat Med Liver Kidney Patterns, 326 Xinshi South Rd, Shijiazhuang 050200, Hebei, Peoples R China.
C3 Chengdu University of Traditional Chinese Medicine; Chengdu University
   of Traditional Chinese Medicine
RP Duan, JG (通讯作者)，Chengdu Univ TCM, Eye Sch, 37 Twelve Bridge Rd, Chengdu 610075, Sichuan, Peoples R China.
EM ineyeduan@126.com
FU Xinglin Scholar Research Promotion Project of Chengdu University of TCM
   [BSH2019007]
FX This work was supported by Xinglin Scholar Research Promotion Project of
   Chengdu University of TCM (grant number BSH2019007).
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NR 42
TC 9
Z9 9
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
EI 1096-0333
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD JAN 1
PY 2021
VL 410
AR 115361
DI 10.1016/j.taap.2020.115361
PG 11
WC Pharmacology & Pharmacy; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy; Toxicology
GA PN9PI
UT WOS:000604805600007
PM 33285147
DA 2022-11-30
ER

PT J
AU Kang, NR
   Pyun, BJ
   Jung, DH
   Lee, IS
   Kim, CS
   Kim, YS
   Kim, JS
AF Kang, Nu Ri
   Pyun, Bo-Jeong
   Jung, Dong Ho
   Lee, Ik Soo
   Kim, Chan-Sik
   Kim, Young Sook
   Kim, Jin Sook
TI Pueraria lobata Extract Protects Hydrogen Peroxide-Induced Human Retinal
   Pigment Epithelial Cells Death and Membrane Permeability
SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
LA English
DT Article
ID OXIDATIVE STRESS; MECHANISMS; RETINOPATHY; DISRUPTION; INDUCTION;
   DEXTRAN; DAMAGE; RADIX
AB Background. Pueraria lobata is used in traditional Asian medicine to treat cardiovascular diseases, diarrhea, diabetes mellitus, and diabetic complications such as diabetic retinopathy. Oxidative stress in retinal pigment epithelial cells is implicated in the pathogenesis of retinopathy and age-related macular degeneration (AMD). Here, we evaluated whether the P. lobata extract can prevent cell death and decrease membrane permeability in oxidative stress-induced human retinal pigment epithelial cells. Methods. The effects of P. lobata extract on hydrogen peroxide- (H2O2-) induced oxidative stress were investigated using 2 ',7 '-dichlorofluorescin diacetate, western blotting, and immunohistochemistry in human retinal pigment epithelial cells. The effects of puerarin, daidzein, and daidzin isolated from P. lobata extract were also studied by determining cell death, reactive oxygen species (ROS) generation, and p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation. Results. Our results showed that the P. lobata extract inhibited ROS generation, suppressed the disruption of zonula occludens-1 (ZO-1), and reduced membrane permeability in H2O2-induced human retinal pigment epithelial cells. Additionally, the P. lobata extract prevented the inhibition of p38 MAPK and JNK phosphorylation. Conclusion. Our findings suggest that the P. lobata extract has the potential to prevent AMD development by inhibiting the mechanism underlying oxidative stress-mediated ocular disorders.
C1 [Kang, Nu Ri; Pyun, Bo-Jeong; Jung, Dong Ho; Lee, Ik Soo; Kim, Chan-Sik; Kim, Young Sook; Kim, Jin Sook] KIOM, Herbal Med Div, Daejeon, South Korea.
   [Kang, Nu Ri; Kim, Young Sook; Kim, Jin Sook] UST, Korean Med Life Sci, 217 Gajeong Ro, Daejeon, South Korea.
   [Kang, Nu Ri] PharmAbcine, Drug Dev Team, Daejeon, South Korea.
   [Lee, Ik Soo; Kim, Young Sook] KIOM, Res Infrastructure Team, Daejeon, South Korea.
   [Kim, Chan-Sik] KIOM, Clin Med Div, Daejeon, South Korea.
C3 Korea Institute of Oriental Medicine (KIOM); University of Science &
   Technology (UST); Korea Institute of Oriental Medicine (KIOM); Korea
   Institute of Oriental Medicine (KIOM)
RP Kim, YS; Kim, JS (通讯作者)，KIOM, Herbal Med Div, Daejeon, South Korea.; Kim, YS; Kim, JS (通讯作者)，UST, Korean Med Life Sci, 217 Gajeong Ro, Daejeon, South Korea.; Kim, YS (通讯作者)，KIOM, Res Infrastructure Team, Daejeon, South Korea.
EM ykim@kiom.re.kr; jskim@kiom.re.kr
OI Kim, Young Sook/0000-0002-5584-402X; jeong, dongho/0000-0002-6250-5720
FU Korea Institute of Oriental Medicine Grant [KSN191171, KSN1812080];
   Korea Institute of Planning and Evaluation for Technology in Food,
   Agriculture, Forestry, and Fisheries (IPET) through the High Value-Added
   Food Technology Development Program; Ministry of Agriculture, Food, and
   Rural Affairs (MAFRA) [317033-03]
FX This work was supported by the Korea Institute of Oriental Medicine
   Grant (KSN191171 and KSN1812080) and the Korea Institute of Planning and
   Evaluation for Technology in Food, Agriculture, Forestry, and Fisheries
   (IPET) through the High Value-Added Food Technology Development Program,
   funded by the Ministry of Agriculture, Food, and Rural Affairs (MAFRA)
   (317033-03).
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NR 33
TC 5
Z9 7
U1 0
U2 3
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 1741-427X
EI 1741-4288
J9 EVID-BASED COMPL ALT
JI Evid.-based Complement Altern. Med.
PD AUG 27
PY 2019
VL 2019
AR 5710289
DI 10.1155/2019/5710289
PG 10
WC Integrative & Complementary Medicine
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Integrative & Complementary Medicine
GA IY5LK
UT WOS:000486433400002
PM 31534464
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Hsu, KS
   Otsu, W
   Li, Y
   Wang, HC
   Chen, SB
   Tsang, SH
   Chuang, JZ
   Sung, CH
AF Hsu, Kuo-Shun
   Otsu, Wataru
   Li, Yao
   Wang, Heuy-Ching
   Chen, Shuibing
   Tsang, Stephen H.
   Chuang, Jen-Zen
   Sung, Ching-Hwa
TI CLIC4 regulates late endosomal trafficking and matrix degradation
   activity of MMP14 at focal adhesions in RPE cells
SO SCIENTIFIC REPORTS
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; 1-MATRIX METALLOPROTEINASE;
   EXTRACELLULAR-MATRIX; INTERPHOTORECEPTOR MATRIX; ENDOCYTIC TRAFFICKING;
   TISSUE INHIBITOR; PLASMA-MEMBRANE; MT1-MMP; EXPRESSION; INVASION
AB Dysregulation in the extracellular matrix (ECM) microenvironment surrounding the retinal pigment epithelium (RPE) has been implicated in the etiology of proliferative vitreoretinopathy and age-related macular degeneration. The regulation of ECM remodeling by RPE cells is not well understood. We show that membrane-type matrix metalloproteinase 14 (MMP14) is central to ECM degradation at the focal adhesions in human ARPE19 cells. The matrix degradative activity, but not the assembly, of the focal adhesion is regulated by chloride intracellular channel 4 (CLIC4). CLIC4 is co-localized with MMP14 in the late endosome. CLIC4 regulates the proper sorting of MMP14 into the lumen of the late endosome and its proteolytic activation in lipid rafts. CLIC4 has the newly-identified "late domain" motif that binds to MMP14 and to Tsg101, a component of the endosomal sorting complex required for transport (ESCRT) complex. Unlike the late domain mutant CLIC4, wild-type CLIC4 can rescue the late endosomal sorting defect of MMP14. Finally, CLIC4 knockdown inhibits the apical secretion of MMP2 in polarized human RPE monolayers. These results, taken together, demonstrate that CLIC4 is a novel matrix microenvironment modulator and a novel regulator for late endosomal cargo sorting. Moreover, the late endosomal sorting of MMP14 actively regulates its surface activation in RPE cells.
C1 [Hsu, Kuo-Shun; Otsu, Wataru; Chuang, Jen-Zen; Sung, Ching-Hwa] Cornell Univ, Dept Ophthalmol, Weill Med Coll, New York, NY 10021 USA.
   [Li, Yao; Tsang, Stephen H.] Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA.
   [Wang, Heuy-Ching] US Army Inst Surg Res, Ocular Trauma Task Area, Joint Base San Antonio Ft Sam Houston, San Antonio, TX USA.
   [Chen, Shuibing] Cornell Univ, Dept Surg, Weill Med Coll, New York, NY 10021 USA.
   [Chen, Shuibing] Cornell Univ, Dept Biochem, Weill Med Coll, New York, NY 10021 USA.
   [Tsang, Stephen H.] Columbia Univ, Inst Human Nutr, Vagelos Coll Phys & Surg, New York, NY 10032 USA.
   [Tsang, Stephen H.] New York Presbyterian Hosp, Edward S Harkness Eye Inst, Jonas Childrens Vis Care & Bernard & Shirlee Brow, New York, NY USA.
   [Tsang, Stephen H.] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY USA.
   [Tsang, Stephen H.] Columbia Univ, Med Ctr, Columbia Stem Cell Initiat, New York, NY USA.
   [Sung, Ching-Hwa] Cornell Univ, Dept Cell & Dev Biol, Weill Med Coll, New York, NY 10021 USA.
   [Hsu, Kuo-Shun] Mem Sloan Kettering Canc Ctr, Dept Surg, Colorectal Serv, New York, NY 10021 USA.
   [Hsu, Kuo-Shun] Mem Sloan Kettering Canc Ctr, Lab Signal Transduct, 1275 York Ave, New York, NY 10021 USA.
   [Otsu, Wataru] Gifu Pharmaceut Univ, Dept Biomed Res Lab, Gifu, Japan.
C3 Cornell University; Columbia University; United States Department of
   Defense; United States Army; Cornell University; Cornell University;
   Columbia University; NewYork-Presbyterian Hospital; Columbia University;
   Columbia University; Cornell University; Memorial Sloan Kettering Cancer
   Center; Memorial Sloan Kettering Cancer Center; Gifu Pharmaceutical
   University
RP Sung, CH (通讯作者)，Cornell Univ, Dept Ophthalmol, Weill Med Coll, New York, NY 10021 USA.; Sung, CH (通讯作者)，Cornell Univ, Dept Cell & Dev Biol, Weill Med Coll, New York, NY 10021 USA.
EM chsung@med.cornell.edu
OI Hsu, Kuo-Shun/0000-0003-4826-506X; Wang, Heuy-Ching/0000-0001-6964-2894;
   Otsu, Wataru/0000-0002-5930-1954
FU NIH [RO1 EY 016805, EY029428]; Research to Prevent Blindness; Bohmfalk
   Charitable Trust; Alcon Research Grant; NATIONAL EYE INSTITUTE
   [R01EY029428] Funding Source: NIH RePORTER
FX We are grateful for the reagents provided by our colleagues (Drs.
   Philippe Chavrier and Francisco SanchezMadrid), the advice in dextran
   uptake experiments (Dr. Frederick Maxfield), the advice in nanopartical
   tracking analysis (Dr. Jae-Hung Shieh) and the usage of NanoSight (Dr.
   Malcom Moore). We also thank for the technical services from Dr. Cheng
   Fu and Ms. Ziqi Guo. This work is supported by NIH RO1 EY 016805,
   EY029428, Research to Prevent Blindness, and Bohmfalk Charitable Trust
   (to C.-H. S.). C.-H. S. is a recipient of Stein Innovation Award from
   Research to Prevent Blindness and Alcon Research Grant.
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NR 99
TC 12
Z9 12
U1 1
U2 4
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD AUG 22
PY 2019
VL 9
AR 12247
DI 10.1038/s41598-019-48438-0
PG 17
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA IS5HC
UT WOS:000482182200022
PM 31439888
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Keeling, E
   Chatelet, DS
   Johnston, DA
   Page, A
   Tumbarello, DA
   Lotery, AJ
   Ratnayaka, JA
AF Keeling, Eloise
   Chatelet, David S.
   Johnston, David A.
   Page, Anton
   Tumbarello, David A.
   Lotery, Andrew J.
   Ratnayaka, J. Arjuna
TI Oxidative Stress and Dysfunctional Intracellular Traffic Linked to an
   Unhealthy Diet Results in Impaired Cargo Transport in the Retinal
   Pigment Epithelium (RPE)
SO MOLECULAR NUTRITION & FOOD RESEARCH
LA English
DT Article
DE cargo trafficking; phagosome and autophagy-lysosomal pathways; oxidative
   stress; retinal pigment epithelium
ID LIPID-PEROXIDATION PRODUCTS; PHOTORECEPTOR OUTER SEGMENTS; MACULAR
   DEGENERATION; LYSOSOMAL ALKALINIZATION; MEDITERRANEAN DIET; AGE PIGMENT;
   CELL-LINE; LIPOFUSCIN; AUTOPHAGY; FAT
AB Scope Oxidative stress and dysregulated intracellular trafficking are associated with an unhealthy diet which underlies pathology. Here, these effects on photoreceptor outer segment (POS) trafficking in the retinal pigment epithelium (RPE), a major pathway of disease underlying irreversible sight-loss, are studied. Methods and results POS trafficking is studied in ARPE-19 cells using an algorithm-based quantification of confocal-immunofluorescence data supported by ultrastructural studies. It is shown that although POS are tightly regulated and trafficked via Rab5, Rab7 vesicles, LAMP1/2 lysosomes and LC3b-autophagosomes, there is also a considerable degree of variation and flexibility in this process. Treatment with H2O2 and bafilomycin A(1) reveals that oxidative stress and dysregulated autophagy target intracellular compartments and trafficking in strikingly different ways. These effects appear limited to POS-containing vesicles, suggesting a cargo-specific effect. Conclusion The findings offer insights into how RPE cells cope with stress, and how mechanisms influencing POS transport/degradation can have different outcomes in the senescent retina. These shed new light on cellular processes underlying retinopathies such as age-related macular degeneration. The discoveries reveal how diet and nutrition can cause fundamental alterations at a cellular level, thus contributing to a better understanding of the diet-disease axis.
C1 [Keeling, Eloise; Lotery, Andrew J.; Ratnayaka, J. Arjuna] Univ Southampton, Clin & Expt Sci, Fac Med, MP806,Tremona Rd, Southampton SO16 6YD, Hants, England.
   [Chatelet, David S.; Johnston, David A.; Page, Anton] Univ Southampton, Biomed Imaging Unit, MP12,Tremona Rd, Southampton SO16 6YD, Hants, England.
   [Tumbarello, David A.] Univ Southampton, Fac Nat & Environm Sci, Biol Sci, Life Sci Bldg 85, Southampton SO17 1B, Hants, England.
   [Lotery, Andrew J.] Univ Hosp Southampton NHS Fdn Trust, Southampton SO16 6YD, Hants, England.
C3 University of Southampton; University of Southampton; University of
   Southampton; University of Southampton; University Hospital Southampton
   NHS Foundation Trust
RP Ratnayaka, JA (通讯作者)，Univ Southampton, Clin & Expt Sci, Fac Med, MP806,Tremona Rd, Southampton SO16 6YD, Hants, England.
EM J.Ratnayaka@soton.ac.uk
OI Ratnayaka, J. Arjuna/0000-0002-1027-6938; Lotery,
   Andrew/0000-0001-5541-4305; Johnston, David/0000-0001-6703-6014;
   Tumbarello, David/0000-0002-5169-0561
FU National Centre for the Replacement, Refinement and Reduction of Animals
   in Research [NC/L001152/1] Funding Source: Medline
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NR 87
TC 9
Z9 9
U1 0
U2 12
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 AUG
PY 2019
VL 63
IS 15
SI SI
AR 1800951
DI 10.1002/mnfr.201800951
PG 18
WC Food Science & Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Food Science & Technology
GA IN8DZ
UT WOS:000478912100014
PM 30835933
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU Naessens, S
   De Zaeytijd, J
   Syx, D
   Vandenbroucke, RE
   Smeets, F
   Van Cauwenberghl, C
   Leroy, BP
   Peelman, F
   Coppieters, F
AF Naessens, Sarah
   De Zaeytijd, Julie
   Syx, Delfien
   Vandenbroucke, Roosmarijn E.
   Smeets, Frederic
   Van Cauwenberghl, Caroline
   Leroy, Bart P.
   Peelman, Frank
   Coppieters, Frauke
TI The N-terminal p.(Ser38Cys) TIMP3 mutation underlying Sorsby fundus
   dystrophy is a founder mutation disrupting an intramolecular disulfide
   bond
SO HUMAN MUTATION
LA English
DT Article
DE aberrant disulfide bonding; dimerization; founder mutation;
   glycosylation; Sorsby fundus dystrophy; TIMP3
ID TISSUE INHIBITOR; METALLOPROTEINASES-3 TIMP3; MATRIX METALLOPROTEINASES;
   GENE; EXPRESSION; STABILITY; PHENOTYPE
AB Sorsby fundus dystrophy (SFD) is a macular degeneration caused by mutations in TIMP3, the majority of which introduce a novel cysteine. However, the exact molecular mechanisms underlying SFD remain unknown. We aimed to provide novel insights into the functional consequences of a distinct N-terminal mutation. Haplotype reconstruction in three SFD families revealed that the identified c.113C>G, p.(Ser38Cys) mutation is a founder in Belgian and northern French families with a late-onset SFD phenotype. Functional consequences of the p.(Ser38Cys) mutation were investigated by high-resolution Western blot analysis of wild type and mutant TIMP3 using patient fibroblasts and in vitro generated proteins, and by molecular modeling of TIMP3 and its interaction partners. We could not confirm a previous hypothesis on dimerization of mutant TIMP3 proteins. However, we identified aberrant intramolecular disulfide bonding. Our data provide evidence for disruption of the established Cys36-Cys143 disulfide bond and formation of a novel Cys36-Cys38 bond, possibly associated with increased glycosylation of the protein. In conclusion, we propose a novel pathogenetic mechanism underlying the p.(Ser38Cys) TIMP3 founder mutation involving intramolecular disulfide bonding. These results provide new insights into the pathogenesis of SFD and other retinopathies linked to mutations in TIMP3, such as age-related macular degeneration.
C1 [Naessens, Sarah; Syx, Delfien; Van Cauwenberghl, Caroline; Leroy, Bart P.; Coppieters, Frauke] Univ Ghent, Ctr Med Genet Ghent, Corneel Heymanslaan 10, B-9000 Ghent, Belgium.
   [Naessens, Sarah; Syx, Delfien; Van Cauwenberghl, Caroline; Leroy, Bart P.; Coppieters, Frauke] Ghent Univ Hosp, Corneel Heymanslaan 10, B-9000 Ghent, Belgium.
   [De Zaeytijd, Julie; Smeets, Frederic; Van Cauwenberghl, Caroline; Leroy, Bart P.] Ghent Univ Hosp, Dept Ophthalmol, Ghent, Belgium.
   [Vandenbroucke, Roosmarijn E.] VIB, VIB Ctr Inflammat Res, Ghent, Belgium.
   [Vandenbroucke, Roosmarijn E.] Univ Ghent, Dept Biomed Mol Biol, Ghent, Belgium.
   [Leroy, Bart P.] Childrens Hosp Philadelphia, Div Ophthalmol, Philadelphia, PA 19104 USA.
   [Peelman, Frank] VIB UGent Ctr Med Biotechnol, Receptor Res Labs, Cytokine Receptor Lab, Ghent, Belgium.
   [Peelman, Frank] Univ Ghent, Dept Biochem, Ghent, Belgium.
C3 Ghent University; Ghent University Hospital; Ghent University; Ghent
   University Hospital; Ghent University; Ghent University Hospital;
   Flanders Institute for Biotechnology (VIB); Ghent University; Ghent
   University; University of Pennsylvania; Pennsylvania Medicine; Childrens
   Hospital of Philadelphia; Flanders Institute for Biotechnology (VIB);
   Ghent University; Ghent University
RP Coppieters, F (通讯作者)，Univ Ghent, Ctr Med Genet Ghent, Corneel Heymanslaan 10, B-9000 Ghent, Belgium.; Coppieters, F (通讯作者)，Ghent Univ Hosp, Corneel Heymanslaan 10, B-9000 Ghent, Belgium.
EM frauke.coppieters@ugent.be
RI De Zaeytijd, Julie/GXA-3099-2022; Vandenbroucke,
   Roosmarijn/AAC-2757-2019; Vandenbroucke, Roosmarijn/B-9419-2009
OI De Zaeytijd, Julie/0000-0003-4035-6389; LEROY, Bart
   Peter/0000-0002-9899-2081; Smeets, Frederic/0000-0002-7191-1456; Syx,
   Delfien/0000-0001-9421-4496; Van Cauwenbergh,
   Caroline/0000-0002-1948-9091; Vandenbroucke,
   Roosmarijn/0000-0002-8327-620X
FU Fund for Scientific Research (FWO), Flanders, Belgium [1S60616N,
   12D8715N, 1515615N, 12Q5917N]
FX Fund for Scientific Research (FWO), Flanders, Belgium (1S60616N,
   12D8715N, 1515615N, 12Q5917N).
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NR 51
TC 7
Z9 7
U1 1
U2 2
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 MAY
PY 2019
VL 40
IS 5
BP 539
EP 551
DI 10.1002/humu.23713
PG 13
WC Genetics & Heredity
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Genetics & Heredity
GA HX0JV
UT WOS:000467076500005
PM 30668888
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU LeBlanc, ME
   Wang, WW
   Ji, YL
   Tian, H
   Liu, DC
   Zhang, XX
   Li, W
AF LeBlanc, Michelle E.
   Wang, Weiwen
   Ji, Yanli
   Tian, Hong
   Liu, Dachuan
   Zhang, Xuxiang
   Li, Wei
TI Secretogranin III as a novel target for the therapy of choroidal
   neovascularization
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Secretogranin III; Scg3; Angiogenic factor; Anti-angiogenic therapy;
   Choroidal neovascularization; CNV; AMD
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; IMMUNOCYTOCHEMICAL
   LOCALIZATION; ANTI-VEGF; RANIBIZUMAB; CELLS; CCR3; INFLAMMATION; MODEL
AB Wet age-related macular degeneration (AMD) with choroidal neovascularization (CNV) is a leading cause of vision loss in the elderly. The advent of anti-vascular endothelial growth factor (VEGF) drugs represents a major breakthrough in wet AMD therapy but with limited efficacy to improve visual acuity. Secretogranin III (Scg3, SgIII) was recently discovered as a novel angiogenic factor with VEGF-independent mechanisms. Scg3-neutralizing monoclonal antibody (mAb) was reported to alleviate pathological retinal neovascularization in oxygen-induced retinopathy mice and retinal vascular leakage in diabetic mice with high efficacy and disease selectivity. Herein we investigated whether Scg3 is a novel angiogenic target for CNV therapy in mouse models. We found that anti-Scg3 ML49.3 mAb inhibited Scg3-induced proliferation and Src phosphorylation in human retinal microvascular endothelial cells. Intravitreal injection of Scg3-neutralizing polyclonal antibodies (pAb) or mAb significantly attenuated laser-induced CNV leakage, CNV 3D volume, lesion area and vessel density. Furthermore, subcutaneous administration of Scg3-neutralizing pAb or mAb significantly prevented Matrigelinduced CNV. The efficacy of anti-Scg3 pAb or mAb was comparable to VEGF inhibitor aflibercept. These findings suggest that Scg3 plays an important role in CNV pathogenesis and that anti-Scg3 mAb efficiently ameliorates laser- or Matrigel-induced CNV.
C1 [LeBlanc, Michelle E.; Wang, Weiwen; Ji, Yanli; Tian, Hong; Li, Wei] Univ Miami, Sch Med, Bascom Palmer Eye Inst, 1638 NW 10th Ave, Miami, FL 33136 USA.
   [Li, Wei] Univ Miami, Vasc Biol Inst, Miami, FL 33136 USA.
   [Ji, Yanli] Zhengzhou Eye Hosp, Dept Ophthalmol, Zhengzhou, Henan, Peoples R China.
   [Tian, Hong] Everlgades Biopharma LLC, Miami, FL USA.
   [Liu, Dachuan; Zhang, Xuxiang] Xuanwu Hosp, Dept Ophthalmol, Beijing, Peoples R China.
C3 Bascom Palmer Eye Institute; University of Miami; University of Miami;
   Capital Medical University
RP Li, W (通讯作者)，Univ Miami, Sch Med, Bascom Palmer Eye Inst, 1638 NW 10th Ave, Miami, FL 33136 USA.
EM w.li@med.miami.edu
FU NIH [P30-EY014801, R01GM094449, R21HD075372, R21EY027065, R41EY027665];
   American Diabetes Association [1-18IBS-172]; Research to Prevent
   Blindness (RPB); American Heart Association Predoctoral Fellowship
   [14PRE18310014, 16PRE27250308]; RPB; NATIONAL EYE INSTITUTE
   [P30EY014801, R21EY027065, R41EY027665] Funding Source: NIH RePORTER
FX We thank Rong Wen, Keith Webster and Philip Rosenfeld for scientific
   advice and discussion; Gabriel Gaidosh for confocal service. Supported
   by NIH R01GM094449 (W.L.), R21HD075372 (W.L.), R21EY027065 (W.L.),
   R41EY027665 (W.L. and H.T.), American Diabetes Association 1-18IBS-172
   (W.L.), Special Scholar Award from Research to Prevent Blindness (RPB)
   (W.L.), American Heart Association Predoctoral Fellowship 14PRE18310014
   and 16PRE27250308 (M.E.L), NIH P30-EY014801 and an institutional grant
   from RPB.
CR [Anonymous], 2011, EYLEA PRESCRIBING IN
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NR 40
TC 9
Z9 9
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 APR
PY 2019
VL 181
BP 120
EP 126
DI 10.1016/j.exer.2019.01.009
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA HT5TJ
UT WOS:000464625900014
PM 30633921
OA Bronze, Green Accepted
DA 2022-11-30
ER

PT J
AU Song, DL
   Ueda, Y
   Bhuyan, R
   Mohammed, I
   Miwa, T
   Gullipali, D
   Kim, H
   Zhou, L
   Song, Y
   Schultz, H
   Bargoud, A
   Dunaief, JL
   Song, WC
AF Song, Delu
   Ueda, Yoshiyasu
   Bhuyan, Rupak
   Mohammed, Imran
   Miwa, Takashi
   Gullipali, Damodar
   Kim, Hangsoo
   Zhou, Lin
   Song, Ying
   Schultz, Hannah
   Bargoud, Albert
   Dunaief, Joshua L.
   Song, Wen-Chao
TI Complement Factor H Mutation W1206R Causes Retinal Thrombosis and
   Ischemic Retinopathy in Mice
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID HEMOLYTIC-UREMIC SYNDROME; OCULAR INVOLVEMENT; PURTSCHER; OCCLUSION;
   MODEL
AB Single-nucleotide polymorphisms and rare mutations in factor H (FH; official name, CFH) are associated with age-related macular degeneration and atypical hemolytic uremic syndrome, a form of thrombotic microangiopathy. Mice with the FH W1206R mutation (FH") share features with human atypical hemolytic uremic syndrome. Herein, we reportthat FH" mice exhibited retinalvascular occlusion and ischemia. Retinal fluorescein angiography demonstrated delayed perfusion and vascular leakage in FH" mice. Optical coherence tomography imaging of FH" mice showed retinal degeneration, edema, and detachment. Histologic analysis of FH" mice revealed retinal thinning, vessel occlusion, as well as degeneration of photoreceptors and retinal pigment epithelium. Immunofluorescence showed albumin Leakage from blood vessels into the neural retina, and electron microscopy demonstrated vascular endothelial cell irregularity with narrowing of retinal and choroidal vessels. Knockout of C6, a component of the membrane attack complex, prevented the aforementioned retinal phenotype in FH" mice, consistent with membrane attack complex mediated pathogenesis. Pharmacologic blockade of C5 also rescued retinas of FH" mice. This FH" mouse strain represents a model for retinal vascular occlusive disorders and ischemic retinopathy. The results suggest complement dysregulation can contribute to retinal vascular occlusion and that an anti-05 antibody might be helpful for C5-mediated thrombotic retinal diseases. (Am Pathol 2019,
C1 [Song, Delu; Bhuyan, Rupak; Song, Ying; Schultz, Hannah; Bargoud, Albert; Dunaief, Joshua L.] Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Ueda, Yoshiyasu; Mohammed, Imran; Miwa, Takashi; Gullipali, Damodar; Kim, Hangsoo; Zhou, Lin; Song, Wen-Chao] Univ Penn, Dept Syst Pharmacol & Translat Therapeut, Perelman Sch Med, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; Pennsylvania Medicine; University of
   Pennsylvania; Pennsylvania Medicine
RP Dunaief, JL (通讯作者)，Univ Penn, Scheie Eye Inst, 305 Stellar Chance Labs,422 Curie Blvd, Philadelphia, PA 19104 USA.; Song, WC (通讯作者)，421 Curie Blvd,Room 1254,BRB 2-3, Philadelphia, PA 19104 USA.
EM jdunaief@pennmedicine.upenn.edu; songwe@pennmedicine.upenn.edu
OI Ueda, Yoshiyasu/0000-0001-5355-5307; Mohammed, Imran/0000-0002-8412-0768
FU NIH [RO1EY023709, RO1AI085596, RO1AI117410, EY023709]; BrightFocus
   Foundation [M2011-051]; Research to Prevent Blindness; F. M. Kirby
   Foundation; Paul and Evanina Bell Mackall Foundation Trust; National
   Center for Advancing Translational Sciences of the NTH [KL2TR001879];
   NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [KL2TR001879]
   Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTE [P30EY001583]
   Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ALLERGY AND
   INFECTIOUS DISEASES [R01AI117410, R01AI085596] Funding Source: NIH
   RePORTER
FX Supported by NIH grants RO1EY023709, RO1AI085596, RO1AI117410, and
   EY023709; a BrightFocus Foundation grant M2011-051 (W.-C.S.); Research
   to Prevent Blindness; the F. M. Kirby Foundation; the Paul and Evanina
   Bell Mackall Foundation Trust; a gift in memory of Dr. Lee F. Mauger
   (J.L.D.); and the National Center for Advancing Translational Sciences
   of the NTH grant KL2TR001879 (D.S.).
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NR 37
TC 3
Z9 3
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 APR
PY 2019
VL 189
IS 4
BP 826
EP 838
DI 10.1016/j.ajpath.2019.01.009
PG 13
WC Pathology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pathology
GA HU1SW
UT WOS:000465053100011
PM 30711487
OA Bronze, Green Published, Green Accepted
DA 2022-11-30
ER

PT J
AU Li, S
   Chaudhary, SC
   Zhao, X
   Gaur, U
   Fang, JK
   Yan, FX
   Zheng, WH
AF Li, Shuai
   Chaudhary, Shubhash Chandra
   Zhao, Xia
   Gaur, Uma
   Fang, Jiankang
   Yan, Fengxia
   Zheng, Wenhua
TI Artemisinin Protects Human Retinal Pigmented Epithelial Cells Against
   Hydrogen Peroxide-induced Oxidative Damage by Enhancing the Activation
   of AMP-active Protein Kinase
SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
LA English
DT Article
DE artemisinin; retinal pigment epithelial cells; oxidative stress; AMPK
ID MACULAR DEGENERATION; SIGNALING PATHWAY; PREVALENCE; MECHANISMS;
   AUTOPHAGY; HOMEOSTASIS; DERIVATIVES; DISEASE; STRESS; BURDEN
AB Dry age-related macular degeneration (AMD), a leading cause of blindness in aged population, is directly associated with oxidative stress induced damage of the retinal pigmented epithelial (RPE) cells. In the current study, we investigated the role of AMPK in the protective effect of artemisinin, an FDA approved anti-malarial Chinese herbal drug, on RPE cell line D407, against H2O2 induced oxidative stress. Our results showed that artemisinin promoted the survival of D407 cells from H2O2. Artemisinin reduced intracellular ROS generation and oxidative stress, decreased LDH release and the loss of mitochondrial membrane potential in D407 cells treated with H2O2. Western blotting showed that artemisinin concentration- and time-dependently stimulated the phosphorylation of AMP-activated protein kinase (AMPK) in D407 cells while AMPK inhibitor Compound C or knock-down of AMPK by si-RNA, inhibited the survival protective effect of artemisinin. More importantly, artemisinin produced a similar protective effect in primary cultured retinal pigment cells which was also blocked by inhibitors of AMPK. Taken together, these results suggested that artemisinin promotes survival of human retinal pigment cells against H2O2-induced cell death at least in part through enhancing the activation of AMPK. Therefore, artemisinin may be a beneficial therapeutic candidate for the treatment of age-related diseases, including retinal disorders like AMD.
C1 [Li, Shuai; Chaudhary, Shubhash Chandra; Zhao, Xia; Gaur, Uma; Fang, Jiankang; Yan, Fengxia; Zheng, Wenhua] Univ Macau, Fac Hlth Sci, Ctr Reprod Dev & Aging, Taipa, Macao, Peoples R China.
   [Li, Shuai; Chaudhary, Shubhash Chandra; Zhao, Xia; Gaur, Uma; Fang, Jiankang; Zheng, Wenhua] Univ Macau, Fac Hlth Sci, Inst Translat Med, Taipa, Macao, Peoples R China.
C3 University of Macau; University of Macau
RP Zheng, WH (通讯作者)，Univ Macau, Fac Hlth Sci, Room 3057,Bldg E12, Taipa, Macao, Peoples R China.
EM wenhuazheng@um.edu.mo
RI Li, Shuai/ABC-5377-2021
FU National Natural Science Foundation of China [31771128]; Science and
   Technology Development Fund (FDCT) of Macao [016/2016/A1, 0113/2018/A3];
   University of Macau [MYRG2016-00052-FHS, MYRG2018-00134-FHS]
FX This research was supported by National Natural Science Foundation of
   China (No. 31771128). The FHS Internal Collaboration Proposals 2017,
   MYRG2016-00052-FHS and MYRG2018-00134-FHS from the University of Macau,
   and the Science and Technology Development Fund (FDCT) of Macao
   (016/2016/A1 and 0113/2018/A3).
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NR 48
TC 9
Z9 9
U1 8
U2 13
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 2019
VL 15
IS 9
BP 2016
EP 2028
DI 10.7150/ijbs.30536
PG 13
WC Biochemistry & Molecular Biology; Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
   Topics
GA IR6VK
UT WOS:000481578100020
PM 31523201
OA gold, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU Atienzar-Aroca, S
   Serrano-Heras, G
   Valls, AF
   de Almodovar, CR
   Muriach, M
   Barcia, JM
   Garcia-Verdugo, JM
   Romero, FJ
   Sancho-Pelluz, J
AF Atienzar-Aroca, Sandra
   Serrano-Heras, Gemma
   Valls, Aida Freire
   de Almodovar, Carmen Ruiz
   Muriach, Maria
   Barcia, Jorge M.
   Garcia-Verdugo, Jose M.
   Romero, Francisco J.
   Sancho-Pelluz, Javier
TI Role of retinal pigment epithelium-derived exosomes and autophagy in new
   blood vessel formation
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Article
DE angiogenesis; autophagy; exosomes; oxidative stress; retina; retinal
   pigment epithelium; siRNA; VEGFR2
ID OXIDATIVE STRESS; CHOROIDAL NEOVASCULARIZATION; FLOW CYTOMETER;
   ANGIOGENESIS; SECRETION; PATHOGENESIS; BIOGENESIS; MECHANISMS;
   EXPRESSION; CELLS
AB Autophagy and exosome secretion play important roles in a variety of physiological and disease states, including the development of age-related macular degeneration. Previous studies have demonstrated that these cellular mechanisms share common pathways of activation. Low oxidative damage in ARPE-19 cells, alters both autophagy and exosome biogenesis. Moreover, oxidative stress modifies the protein and genetic cargo of exosomes, possibly affecting the fate of surrounding cells. In order to understand the connection between these two mechanisms and their impact on angiogenesis, stressed ARPE-19 cells were treated with a siRNA-targeting Atg7, a key protein for the formation of autophagosomes. Subsequently, we observed the formation of multivesicular bodies and the release of exosomes. Released exosomes contained VEGFR2 as part of their cargo. This receptor for VEGF-which is critical for the development of new blood vessels-was higher in exosome populations released from stressed ARPE-19. While stressed exosomes enhanced tube formation, exosomes became ineffective after silencing VEGFR2 in ARPE-19 cells and were, consequently, unable to influence angiogenesis. Moreover, vessel sprouting in the presence of stressed exosomes seems to follow a VEGF-independent pathway. We propose that abnormal vessel growth correlates with VEGFR2-expressing exosomes release from stressed ARPE-19 cells, and is directly linked to autophagy.
C1 [Atienzar-Aroca, Sandra; Barcia, Jorge M.; Sancho-Pelluz, Javier] Catholic Univ Valencia, Sch Med, Valencia, Spain.
   [Serrano-Heras, Gemma] Gen Univ Hosp Albacete, Expt Res Unit, Albacete, Spain.
   [Valls, Aida Freire; de Almodovar, Carmen Ruiz] Heidelberg Univ, Heidelberg Biochem Zentrum BZH, Heidelberg, Germany.
   [Muriach, Maria] Univ Jaume 1, Unidad Predept Med, Castellon De La Plana, Spain.
   [Garcia-Verdugo, Jose M.] Univ Valencia, Dept Comparat Neurobiol, Valencia, Spain.
   [Romero, Francisco J.] Univ Europea Valencia, Fac Hlth Sci, Valencia, Spain.
C3 Universidad Catolica de Valencia San Vicente Martir; Ruprecht Karls
   University Heidelberg; Universitat Jaume I; University of Valencia
RP Romero, FJ (通讯作者)，Univ Europea Valencia, Fac Hlth Sci, Valencia, Spain.
EM franciscojavier.romero@universidadeuropea.es
RI Muriach, María/AAB-2003-2019; García-Verdugo, José Manuel/L-8421-2017;
   Sancho-Pelluz, Javier/AAB-2786-2019; JM, Barcia/ABH-2932-2020
OI García-Verdugo, José Manuel/0000-0001-9872-6499; Sancho-Pelluz,
   Javier/0000-0001-5409-5760; Barcia, Jorge M./0000-0002-3660-7977;
   Serrano-Heras, Gemma/0000-0001-9368-4832; Ruiz de Almodovar,
   Carmen/0000-0001-5975-7815; Romero, Francisco J/0000-0001-8701-5907
FU Generalitat Valenciana [94/2016]
FX Generalitat Valenciana, Grant/Award Number: Prometeo #94/2016
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NR 54
TC 25
Z9 28
U1 1
U2 15
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
EI 1582-4934
J9 J CELL MOL MED
JI J. Cell. Mol. Med.
PD NOV
PY 2018
VL 22
IS 11
BP 5244
EP 5256
DI 10.1111/jcmm.13730
PG 13
WC Cell Biology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology; Research & Experimental Medicine
GA GY1IF
UT WOS:000448279600007
PM 30133118
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Choudhary, M
   Safe, S
   Malek, G
AF Choudhary, Mayur
   Safe, Stephen
   Malek, Goldis
TI Suppression of aberrant choroidal neovascularization through activation
   of the aryl hydrocarbon receptor
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
LA English
DT Article
DE Aryl hydrocarbon receptor; Choroidal neovascularization; Inflammation;
   Extracellular matrix; Angiogenesis; Selective receptor modulators
ID MACULAR DEGENERATION; EXTRACELLULAR-MATRIX; THERAPEUTIC TARGETS; VISUAL
   IMPAIRMENT; NUCLEAR RECEPTORS; PREVALENCE; DIFFERENTIATION;
   ANGIOGENESIS; EXPRESSION; MEMBRANES
AB The aryl hydrocarbon receptor (AhR) is a ligand activated transcription factor, initially discovered for its role in regulating xenobiotic metabolism. There is extensive evidence supporting a multi-faceted role for AhR, modulating physiological pathways important in cell health and disease. Recently we demonstrated that the AhR plays a role in the pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly. We found that loss of AhR exacerbates choroidal neovascular (CNV) lesion formation in a murine model. Herein we tested the therapeutic impact of AhR activation on CNV lesion formation and factors associated with aberrant neovascularization. We screened a panel of synthetic drugs and endogenous AhR ligands, assessed their ability to activate AhR in choroidal endothelial cells, and inhibit angiogenesis in vitro. Drugs with an anti-angiogenic profile were then administered to a murine model of CNV. Two compounds, leflunomide and flutamide, significantly inhibited CNV formation concurrent with positive modifying effects on angiogenesis, inflammation, extracellular matrix remodeling, and fibrosis. These results validate the role of the AhR pathway in regulating CNV pathogenesis, identify mechanisms of AhR-based therapies in the eye, and argue in favor of developing AhR as a drug target for the treatment of neovascular AMD.
C1 [Choudhary, Mayur; Malek, Goldis] Duke Univ, Sch Med, Dept Ophthalmol, 2351 Erwin Rd,POB 3802,Room 4006, Durham, NC 27710 USA.
   [Safe, Stephen] Texas A&M Univ, Vet Med & Biomed Sci, College Stn, TX USA.
   [Malek, Goldis] Duke Univ, Sch Med, Dept Pathol, Durham, NC 27710 USA.
C3 Duke University; Texas A&M University System; Texas A&M University
   College Station; Duke University
RP Malek, G (通讯作者)，Duke Univ, Sch Med, Dept Ophthalmol, 2351 Erwin Rd,POB 3802,Room 4006, Durham, NC 27710 USA.
EM gmalek@duke.edu
RI Choudhary, Mayur/AAU-3497-2021
OI Choudhary, Mayur/0000-0001-8056-011X; Malek, Goldis/0000-0003-0026-2388
FU National Eye Institute [EY02868, P30 EY005722]; Edward N. AMP; Della L.
   Thome Memorial Foundation Award; BrightFocus Macular Degeneration Grant;
   Research to Prevent Blindness, Inc. (RPB) Core grant; NATIONAL EYE
   INSTITUTE [R01EY020868, P30EY005722] Funding Source: NIH RePORTER
FX This research was supported by the National Eye Institute grants EY02868
   (to GM) and P30 EY005722 (to the Duke Eye Center), the Edward N. & Della
   L. Thome Memorial Foundation Award, BrightFocus Macular Degeneration
   Grant and the Research to Prevent Blindness, Inc. (RPB) Core grant.
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NR 84
TC 13
Z9 13
U1 1
U2 5
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0925-4439
EI 1879-260X
J9 BBA-MOL BASIS DIS
JI Biochim. Biophys. Acta-Mol. Basis Dis.
PD MAY
PY 2018
VL 1864
IS 5
BP 1583
EP 1595
DI 10.1016/j.bbadis.2018.02.015
PN A
PG 13
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA GE0DB
UT WOS:000430883100005
PM 29481912
OA Green Accepted, Bronze
DA 2022-11-30
ER

PT J
AU Hussain, RM
   Gregori, NZ
   Ciulla, TA
   Lam, BL
AF Hussain, Rehan M.
   Gregori, Ninel Z.
   Ciulla, Thomas A.
   Lam, Byron L.
TI Pharmacotherapy of retinal disease with visual cycle modulators
SO EXPERT OPINION ON PHARMACOTHERAPY
LA English
DT Review
DE 9-cis-retinyl-acetate; C20-D3-vitamin A; emixustat; fenretinide;
   geographic atrophy; Leber's congenital amaurosis; retinitis pigmentosa;
   Stargardt macular dystrophy; visual cycle
ID LEBER CONGENITAL AMAUROSIS; VITAMIN-A; GEOGRAPHIC ATROPHY; GENE-THERAPY;
   MOUSE MODEL; LIPOFUSCIN ACCUMULATION; ACUITY LOSS; OPEN-LABEL; PIGMENT;
   ROD
AB Introduction: Pharmacotherapy with visual cycle modulators (VCMs) is under investigation for retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), Stargardt macular dystrophy (SMD) and nonexudative age-related macular degeneration (AMD), all blinding diseases that lack effective treatment options.Areas covered: The authors review investigational VCMs, including oral retinoids, 9-cis-retinyl-acetate (zuretinol) and 9-cis--carotene, which restore 11-cis-retinal levels in RP and LCA caused by LRAT and RPE65 gene mutations, and may improve visual acuity and visual fields. Therapies for SMD aiming to decrease accumulation of toxic Vitamin A dimers and lipofuscin in the retina and retinal pigment epithelium (RPE) include C20-D3-vitamin A (ALK-001), isotretinoin, VM200, emixustat, and A1120. Mouse models of SMD show promising data for these treatments, though proof of efficacy in humans is currently lacking. Fenretinide and emixustat are investigational VCMs for dry AMD, though neither has been shown to reduce geographic atrophy or improve vision in human trials. A1120 prevents retinol transport into the RPE and may spare the side effects typically seen in VCMs (nyctalopia and chromatopsia) per mouse studies.Expert opinion: Oral VCMs may be feasible treatment options for degenerative retinal diseases based on pre-clinical and some early clinical studies. Further trials are warranted to assess their efficacy and safety in humans.
C1 [Hussain, Rehan M.; Gregori, Ninel Z.; Lam, Byron L.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, 900 NW 17th St, Miami, FL 33136 USA.
   [Ciulla, Thomas A.] Midwest Eye Inst, Dept Ophthalmol, Retina Serv, Indianapolis, IN USA.
   [Ciulla, Thomas A.] Indiana Univ Sch Med, Retina Serv, Indianapolis, IN 46202 USA.
C3 Bascom Palmer Eye Institute; University of Miami; Indiana University
   System; Indiana University Bloomington
RP Hussain, RM (通讯作者)，Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, 900 NW 17th St, Miami, FL 33136 USA.
EM rhussain27@med.miami.edu
RI Ciulla, Thomas/AAA-1299-2020
OI Ciulla, Thomas/0000-0001-5557-6777
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NR 68
TC 22
Z9 22
U1 0
U2 14
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1465-6566
EI 1744-7666
J9 EXPERT OPIN PHARMACO
JI Expert Opin. Pharmacother.
PY 2018
VL 19
IS 5
BP 471
EP 481
DI 10.1080/14656566.2018.1448060
PG 11
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA GA1CF
UT WOS:000428052300007
PM 29542350
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Rasul, A
   Subhi, Y
   Sorensen, TL
   Munch, IC
AF Rasul, Asrin
   Subhi, Yousif
   Sorensen, Torben Lykke
   Munch, Inger Christine
TI Non-physician delivered intravitreal injection service is feasible and
   safe - a systematic review
SO DANISH MEDICAL JOURNAL
LA English
DT Review
ID MACULAR DEGENERATION; VISUAL IMPAIRMENT; RANIBIZUMAB; PREVALENCE; TIME;
   BLINDNESS; NURSES; DELAY
AB INTRODUCTION: Non-physicians such as nurses are trained to give injections into the vitreous body of the eye to meet the increasing demand for intravitreal therapy with vascular endothelial growth factor inhibitors against common eye diseases, e.g. age-related macular degeneration and diabetic retinopathy. We systematically reviewed the existing literature to provide an overview of the experiences in this transformational process.
   METHODS: We searched for literature on 22 September 2015 using PubMed, Embase, the Cochrane Library, CINAHL and the Web of Science. Eligible studies had to address any outcome based on non-physician delivered intravitreal therapy regardless of the study design. Being non-physician was defined as the injecting personnel not being a physician, but no further restrictions were made.
   RESULTS: Five studies were included with a total of 31,303 injections having been performed by 16 nurses. The studies found that having nurses perform the intravitreal injections produced to a short-term capacity improvement and liberated physicians for other clinical work. Training was provided through courses and direct supervision. The rates of endophthalmitis were 0-0.40%, which is comparable to reported rates when the intravitreal therapy is given by physicians.
   CONCLUSION: Non-physician delivered intravitreal therapy seems feasible and safe.
C1 [Rasul, Asrin; Subhi, Yousif; Sorensen, Torben Lykke; Munch, Inger Christine] Zealand Univ Hosp, Dept Ophthalmol, Roskilde, Denmark.
   [Subhi, Yousif; Sorensen, Torben Lykke; Munch, Inger Christine] Univ Copenhagen, Fac Hlth & Med Sci, DK-1168 Copenhagen, Denmark.
C3 University of Copenhagen
RP Subhi, Y (通讯作者)，Zealand Univ Hosp, Dept Ophthalmol, Roskilde, Denmark.; Subhi, Y (通讯作者)，Univ Copenhagen, Fac Hlth & Med Sci, DK-1168 Copenhagen, Denmark.
EM ysubhi@gmail.com
RI Subhi, Yousif/ABG-6330-2020; Munch, Inger Christine/E-9652-2010
OI Subhi, Yousif/0000-0001-6620-5365; 
CR [Anonymous], 2015, MOORFIELDS UNVEILS N
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NR 38
TC 13
Z9 13
U1 0
U2 0
PU DANISH MEDICAL ASSOC
PI COPENHAGEN
PA TRONDHJEMSGADE 9, DK-2100 COPENHAGEN, DENMARK
EI 2245-1919
J9 DAN MED J
JI Dan. Med. J.
PD MAY
PY 2016
VL 63
IS 5
AR A5229
PG 6
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA ED7HA
UT WOS:000389032000005
PM 27127016
DA 2022-11-30
ER

PT J
AU Rabhi, C
   Arcile, G
   Cariel, L
   Lenoir, C
   Bignon, J
   Wdzieczak-Bakala, J
   Ouazzani, J
AF Rabhi, Cherif
   Arcile, Guillaume
   Cariel, Leon
   Lenoir, Christine
   Bignon, Jerome
   Wdzieczak-Bakala, Joanna
   Ouazzani, Jamal
TI Antiangiogenic-Like Properties of Fermented Extracts of Ayurvedic
   Medicinal Plants
SO JOURNAL OF MEDICINAL FOOD
LA English
DT Article
DE angiogenesis; fermentation; Emblica officinalis; Bacopa monnieri;
   Withania somnifera; age-related macular degeneration; Beauveria bassiana
ID ENDOTHELIAL-GROWTH-FACTOR; BEAUVERIA-BASSIANA; WITHANIA-SOMNIFERA;
   ANGIOGENESIS; IDENTIFICATION; INFLAMMATION; FORMULATION; INHIBITOR;
   DISEASE; TRIALS
AB The three ayurvedic medicinal plants, Withania somnifera, Emblica officinalis, and Bacopa monnieri, were extracted by high-pressure static extraction using the Zippertex((R)) technology. The extracts were mixed to reach quantifiable amounts of active compounds identified by high-pressure liquid chromatography-mass spectrometry (HPLC-MS) analysis. The mixture of extracts was incubated with resting cells of the fungus Beauveria bassiana ATCC 7159. The fermentation promoted the fluidization of the starting dense mixture, while HPLC monitoring evidenced the disappearance of glucogallin from E. officinalis extract and the concomitant increase in gallic acid content. Topical exposure of the chick embryo chorioallantoic membrane (CAM) to the nonfermented extract led to the extensive necrosis and destruction of the treated membrane. However, the fermented extract was shown to be free of any toxicity. Furthermore, compared with the untreated CAM, the fermented sample reduced CAM vascularization, suggesting its antiangiogenic potency. The innocuity of the fermented extract was demonstrated using the in vivo LD50 test, the morphological examination of internal organs of treated rats, as well as the evaluation of blood biomarkers of liver damage (aspartate aminotransferase and alanine aminotransferase). The fermented extract was developed as a nutraceutical antiangiogenic treatment of age-related macular degeneration and commercialized in an oral form named Ethnodyne-Visio (TM).
C1 [Rabhi, Cherif; Cariel, Leon] Ethnodyne, Paris, France.
   [Arcile, Guillaume; Lenoir, Christine; Bignon, Jerome; Wdzieczak-Bakala, Joanna; Ouazzani, Jamal] Ctr Natl Rech Sci CNRS, Inst Chim Subst Nat ICSN, Ctr Rech Gif, F-91198 Gif Sur Yvette, France.
C3 Centre National de la Recherche Scientifique (CNRS); UDICE-French
   Research Universities; Universite Paris Saclay
RP Ouazzani, J (通讯作者)，Ctr Natl Rech Sci CNRS, Inst Chim Subst Nat ICSN, Ave Terrasse, F-91198 Gif Sur Yvette, France.
EM Jamal.ouazzani@cnrs.fr
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NR 38
TC 10
Z9 10
U1 0
U2 15
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1096-620X
EI 1557-7600
J9 J MED FOOD
JI J. Med. Food
PD SEP 1
PY 2015
VL 18
IS 9
BP 1065
EP 1072
DI 10.1089/jmf.2014.0128
PG 8
WC Chemistry, Medicinal; Food Science & Technology; Nutrition & Dietetics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy; Food Science & Technology; Nutrition &
   Dietetics
GA CQ9XG
UT WOS:000360968100014
PM 25608021
DA 2022-11-30
ER

PT J
AU Ben M'Barek, K
   Regent, F
   Monville, C
AF Ben M'Barek, Karim
   Regent, Florian
   Monville, Christelle
TI Use of human pluripotent stem cells to study and treat retinopathies
SO WORLD JOURNAL OF STEM CELLS
LA English
DT Review
DE Drug screening; Human pluripotent stem cells; Disease modeling;
   Retinitis pigmentosa
ID RETINAL-PIGMENT EPITHELIUM; DOMINANT RETINITIS-PIGMENTOSA; VESICLE-LIKE
   STRUCTURES; HUMAN IPS CELLS; GENE-THERAPY; FUNCTIONAL-ANALYSIS;
   MOLECULAR CHARACTERIZATION; SOMATIC-CELLS; ANIMAL-MODELS; NEURAL RETINA
AB Human cell types affected by retinal diseases (such as age-related macular degeneration or retinitis pimentosa) are limited in cell number and of reduced accessibility. As a consequence, their isolation for in vitro studies of disease mechanisms or for drug screening efforts is fastidious. Human pluripotent stem cells (hPSCs), either of embryonic origin or through reprogramming of adult somatic cells, represent a new promising way to generate models of human retinopathies, explore the physiopathological mechanisms and develop novel therapeutic strategies. Disease-specific human embryonic stem cells were the first source of material to be used to study certain disease states. The recent demonstration that human somatic cells, such as fibroblasts or blood cells, can be genetically converted to induce pluripotent stem cells together with the continuous improvement of methods to differentiate these cells into disease-affected cellular subtypes opens new perspectives to model and understand a large number of human pathologies, including retinopathies. This review focuses on the added value of hPSCs for the disease modeling of human retinopathies and the study of their molecular pathological mechanisms. We also discuss the recent use of these cells for establishing the validation studies for therapeutic intervention and for the screening of large compound libraries to identify candidate drugs.
C1 [Ben M'Barek, Karim; Regent, Florian; Monville, Christelle] I Stem, INSERM, AFM, UMR861, 5 Rue Henri Desbrueres,Genopole Campus 1, F-91030 Evry, France.
   [Ben M'Barek, Karim; Regent, Florian; Monville, Christelle] I Stem, UEVE, UMR861, AFM, F-91030 Evry, France.
C3 Genopole; Institut National de la Sante et de la Recherche Medicale
   (Inserm); UDICE-French Research Universities; Universite Paris Saclay;
   UDICE-French Research Universities; Universite Paris Saclay
RP Monville, C (通讯作者)，I Stem, INSERM, AFM, UMR861, 5 Rue Henri Desbrueres,Genopole Campus 1, F-91030 Evry, France.
EM cmonville@istem.fr
RI M'BAREK, Karim BEN/K-1389-2019
OI M'BAREK, Karim BEN/0000-0002-2556-0325; Monville,
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NR 103
TC 6
Z9 6
U1 0
U2 2
PU BAISHIDENG PUBLISHING GROUP INC
PI PLEASANTON
PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA
SN 1948-0210
J9 WORLD J STEM CELLS
JI World J. Stem Cells
PD APR 26
PY 2015
VL 7
IS 3
BP 596
EP 604
DI 10.4252/wjsc.v7.i3.596
PG 9
WC Cell & Tissue Engineering; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA V64PF
UT WOS:000211112200007
PM 25914766
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Zhu, W
   Wu, Y
   Meng, YF
   Wang, JY
   Xu, M
   Tao, JJ
   Lu, J
AF Zhu, Wei
   Wu, Yan
   Meng, Yi-Fang
   Wang, Jin-Yu
   Xu, Ming
   Tao, Jian-Jun
   Lu, Jiong
TI Effect of curcumin on aging retinal pigment epithelial cells
SO DRUG DESIGN DEVELOPMENT AND THERAPY
LA English
DT Article
DE curcumin; retinal pigment epithelium; apoptosis; age-related macular
   degeneration
ID MACULAR DEGENERATION; OXIDATIVE STRESS; EXPRESSION; RISK
AB Age-related macular degeneration (AMD) is now one of the leading causes of blindness in the elderly population. The antioxidative effects of curcumin on aging retinal pigment epithelial (RPE) cells are still unclear. We conducted an in vitro study to investigate the effects of curcumin on aging RPE cells. A pulsed H2O2 exposure aging model was adopted. Aging RPE cells were treated with curcumin 20 mu M, 40 mu M, and 80 mu M. Apoptosis of RPE cells was analyzed by flow cytometry. The intracellular reactive oxygen species concentration was detected using a specific probe and apoptosis-associated proteins were detected by Western blot. Expression of oxidative biomarkers, including superoxide dismutase, maleic dialdehyde, and glutathione, was detected commercially available assay kits. Compared with normal cells, lower cell viability, higher apoptosis rates, and more severe oxidation status were identified in the aging RPE cell model. Curcumin improved cell viability and decreased apoptosis and oxidative stress. Further, curcumin had a significant influence on expression of apoptosis-associated proteins and oxidative stress biomarkers. In conclusion, treatment with curcumin was able to regulate proliferation, oxidative stress, and apoptosis in aging RPE cells. Accordingly, application of curcumin may be a novel strategy to protect against age-related change in AMD.
C1 [Zhu, Wei; Meng, Yi-Fang; Wang, Jin-Yu; Xu, Ming; Tao, Jian-Jun; Lu, Jiong] Changshu 2 Peoples Hosp, Dept Ophthalmol, Changshu 215000, Jiangsu, Peoples R China.
   [Wu, Yan] Jiangsu Univ, Peoples Hosp Kunshan 1, Dept Ophthalmol, Suzhou, Peoples R China.
C3 Jiangsu University
RP Lu, J (通讯作者)，Changshu 2 Peoples Hosp, Dept Ophthalmol, Haiyu South Rd 68, Changshu 215000, Jiangsu, Peoples R China.
EM cslujiong@163.com
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NR 25
TC 40
Z9 43
U1 1
U2 6
PU DOVE MEDICAL PRESS LTD
PI ALBANY
PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND
SN 1177-8881
J9 DRUG DES DEV THER
JI Drug Des. Dev. Ther.
PY 2015
VL 9
BP 5337
EP 5344
DI 10.2147/DDDT.S84979
PG 8
WC Chemistry, Medicinal; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA CS1AW
UT WOS:000361795100001
PM 26445530
OA Green Published, gold, Green Submitted
DA 2022-11-30
ER

PT J
AU Qin, SF
   Lu, YM
   Rodrigues, GA
AF Qin, Suofu
   Lu, Yimin
   Rodrigues, Gerard A.
TI Resveratrol protects RPE cells from sodium iodate by modulating PPAR
   alpha and PPAR delta
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE PPAR; resveratrol; ROS; RPE; sodium iodate; survival
ID PIGMENT EPITHELIAL-CELLS; ACTIVATED RECEPTOR-ALPHA; PHOTORECEPTOR OUTER
   SEGMENTS; MACULAR DEGENERATION; OXIDATIVE STRESS; TRANS-RESVERATROL;
   INDUCED DAMAGE; INHIBITION; PATHWAYS; MICE
AB Selective killing of RPE cells in vivo by sodium iodate develops cardinal phenotypes of atrophic age-related macular degeneration. However, the molecular mechanisms are elusive. We tried to search for small cyto-protective molecules against sodium iodate and explore their mechanisms of action. Sodium iodate-mediated RPE cell death was associated with increased levels of reactive oxygen species (ROS) and IL-8. Resveratrol, a natural occurring polyphenol compound, was found to strongly protect RPE cells from sodium iodate with inhibition of production of ROS and IL-8. Resveratrol activated all isoforms of PPARs. Treatment with PPAR alpha and PPAR delta agonists inhibited sodium iodate-induced ROS production and protected RPE cells from sodium iodate. A PPAR alpha antagonist significantly reduced resveratrol's protection of RPE cells from sodium iodate. Paradoxically, knocking down PPAR delta also rendered RPE cells resistant to sodium iodate. Moreover, PPAR agonists reversed sodium iodate-induced production of IL-8. However, neutralizing extracellular IL-8 failed to protect RPE cells from sodium iodate. Taken together, these observations show that resveratrol protects RPE cells from sodium iodate injury through the activation of PPAR alpha and alteration of PPAR delta conformation. PPAR alpha and delta modulators might ameliorate stress-induced RPE degeneration in vivo. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Qin, Suofu; Lu, Yimin; Rodrigues, Gerard A.] Allergan Pharmaceut Inc, Dept Biol Sci, Irvine, CA 92612 USA.
C3 AbbVie; Allergan
RP Qin, SF (通讯作者)，Allergan Pharmaceut Inc, Dept Biol Sci, RD3-2D,2525 Dupont Dr, Irvine, CA 92612 USA.
EM qin_suofu@allergan.com
RI Feagan, Brian G/M-4283-2015
OI Qin, Suofu/0000-0002-3323-8846
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TC 24
Z9 24
U1 1
U2 7
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD JAN
PY 2014
VL 118
BP 100
EP 108
DI 10.1016/j.exer.2013.11.010
PG 9
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 297NI
UT WOS:000330261800013
PM 24309288
DA 2022-11-30
ER

PT J
AU Lee, Y
   Kim, J
   Jo, K
   Shin, SD
   Kim, CS
   Sohn, EJ
   Kim, SG
   Kim, JS
AF Lee, Yunmi
   Kim, Junghyun
   Jo, Kyuhyung
   Shin, So Dam
   Kim, Chan-Sik
   Sohn, Eun Jin
   Kim, Seon Gi
   Kim, Jin Sook
TI Ethyl Pyruvate Inhibits Retinal Pathogenic Neovascularization by
   Downregulating HMGB1 Expression
SO JOURNAL OF DIABETES RESEARCH
LA English
DT Article
ID MOBILITY GROUP BOX-1; DIABETIC-RETINOPATHY; NAD(P)H OXIDASE;
   GENE-EXPRESSION; GROWTH-FACTOR; ISCHEMIA; RELEASE; PROTEIN;
   ANGIOGENESIS; INFLAMMATION
AB Retinal pathogenic angiogenesis in the eyes is a causative factor in retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. This study was designed to examine the pathogenic role of the high-mobility group box-1 (HMGB1) protein and the inhibitory effect of ethyl pyruvate (EP), a well-known antioxidant substance, in retinal pathogenic angiogenesis in mice with oxygen-induced retinopathy (OIR), one of the animal models of proliferative ischemic retinopathy. The OIR mouse model was used for our in vivo studies. The mice were exposed to 75% oxygen from postnatal day 7 (P7) to P11, after which the mice were brought to room air and intraperitoneally injected with EP (50 mg/kg, or 100 mg/kg) for five days. At P17, the mice were perfused with fluorescein isothiocyanate-dextran, and flat-mounted retinas were used to measure nonperfused and neovascular tufts. In OIR mice, an intraperitoneal injection of EP reduced the nonperfused retinal area in the treatment group and significantly reduced the retinal neovascular tufts. In addition, EP inhibited the overexpression of HMGB1 in the retinas of OIR mice. These data suggest that EP could serve as an innovative pharmaceutical agent to prevent retinal neovascularization through inhibiting HMGB1 expression.
C1 [Lee, Yunmi; Kim, Junghyun; Jo, Kyuhyung; Shin, So Dam; Kim, Chan-Sik; Sohn, Eun Jin; Kim, Seon Gi; Kim, Jin Sook] Korea Inst Oriental Med, Herbal Med Res Div, Korean Med Based Herbal Drug Dev Grp, Taejon 305811, South Korea.
C3 Korea Institute of Oriental Medicine (KIOM)
RP Kim, JS (通讯作者)，Korea Inst Oriental Med, Herbal Med Res Div, Korean Med Based Herbal Drug Dev Grp, 1672 Yuseongdaero, Taejon 305811, South Korea.
EM jskim@kiom.re.kr
FU Korea Institute of Oriental Medicine (KIOM) [K13040]
FX This research was supported a grant [K13040] from the Korea Institute of
   Oriental Medicine (KIOM).
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NR 46
TC 21
Z9 22
U1 0
U2 0
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND
SN 2314-6745
EI 2314-6753
J9 J DIABETES RES
JI J. Diabetes Res.
PY 2013
VL 2013
AR 245271
DI 10.1155/2013/245271
PG 8
WC Endocrinology & Metabolism; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Endocrinology & Metabolism; Research & Experimental Medicine
GA 265MF
UT WOS:000327955300001
PM 24371837
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Dick, AD
AF Dick, Andrew D.
TI Road to Fulfilment: Taming the Immune Response to Restore Vision
SO OPHTHALMIC RESEARCH
LA English
DT Review
DE Experimental auto-immune uveoretinitis; Auto-immune response;
   Inflammation; Macrophage; Angiogenesis; Auto-immunity
ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; RETINAL MICROGLIA; MACROPHAGE
   ACTIVATION; CELLULAR INFILTRATE; RESIDENT MICROGLIA; CELLS; RECEPTOR;
   POLYMORPHISM; ASSOCIATION; EXPRESSION
AB While traditionally considered to be an immune privileged site, the eye, and in particular the retina, is nonetheless endowed with immune-competent cells capable of engaging powerful immune regulatory networks. By understanding the mechanisms that promote immune well-being in the eye, we are able to generate therapies which combat undue immune-mediated damage not only by revealing mechanisms that promote tissue damage, but also by an ability to restore tissue immune homeostasis by harnessing intrinsic immune-regulatory mechanisms. The result is to maintain or restore immune health as well as combat tissue damage evoked during, for example, intra-ocular inflammatory disease (uveitis), angiogenesis (age-related macular degeneration) and retinal degenerative disorders. Immune activation and regulation is a balance that is dictated by cognate and soluble factors at both a tissue and cellular level. These continuously respond to and eradicate danger and pathogenic signals whilst maintaining tissue function by controlling, and not exclusively, vascular barriers, complement activation, macrophage activation and keeping in check local T cell proliferation. Loss of the balance between activation and inhibitory signals leads to uncontrolled tissue damage. Understanding the mechanisms has gained potential therapeutic opportunities not only to suppress on-going inflammation, but also to restore homeostasis and prevent recrudescence. Copyright (c) 2012 S. Karger AG, Basel
C1 [Dick, Andrew D.] Univ Bristol, Sch Clin Sci, Bristol, Avon, England.
   [Dick, Andrew D.] Univ Bristol, Sch Cellular & Mol Med, Bristol, Avon, England.
   [Dick, Andrew D.] Moorfields Eye Hosp NHS Fdn Trust, Natl Inst Hlth Res, Biomed Res Ctr Ophthalmol, London, England.
   [Dick, Andrew D.] UCL Inst Ophthalmol, London, England.
C3 University of Bristol; University of Bristol; University of London;
   University College London; Moorfields Eye Hospital NHS Foundation Trust;
   University of London; University College London
RP Dick, AD (通讯作者)，Bristol Eye Hosp, Lower Maudlin St, Bristol BS1 2LX, Avon, England.
EM a.dick@bristol.ac.uk
OI Dick, Andrew/0000-0002-0742-3159
FU Dunhill Medical Trust; National Eye Research Centre; Underwood Trust;
   Institutes of Novartis BioMedical Research
FX This work was presented as the Ophthalmic Research Lecture at European
   Vision and Eye Research Association annual meeting in Crete, 2011. Work
   presented is supported from grants awarded by Dunhill Medical Trust and
   National Eye Research Centre and Underwood Trust. FTY270 work was
   supported by an investigator grant from Institutes of Novartis
   BioMedical Research. I am indebted to Dr. Richard Lee for critical
   reading of the manuscript.
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NR 59
TC 12
Z9 12
U1 0
U2 5
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3747
EI 1423-0259
J9 OPHTHALMIC RES
JI Ophthalmic Res.
PY 2012
VL 48
IS 1
BP 43
EP 49
DI 10.1159/000335982
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 962NF
UT WOS:000305551100008
PM 22398563
OA Bronze
DA 2022-11-30
ER

PT J
AU Lee, EJ
   Kim, N
   Kang, KH
   Kim, JW
AF Lee, Eun Jung
   Kim, Namsuk
   Kang, Kyung Hwa
   Kim, Jin Woo
TI Phosphorylation/inactivation of PTEN by Akt-independent PI3K signaling
   in retinal pigment epithelium
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE PTEN; PI3K-Akt signaling; Oxidative stress; Retinal pigment epithelium
   (RPE); Age-related macular degeneration
ID SODIUM IODATE; MACULAR DEGENERATION; MODEL; DYSFUNCTION; ACTIVATION;
   MECHANISMS; LIPOFUSCIN; APOPTOSIS; PROTEINS; PATHWAY
AB Retinal pigment epithelium (RPE) plays a critical role in vertebrate vision by providing functional and structural support to the retina. Degeneration of RPE by cumulative oxidative stresses or acute injury frequently results in retinal degenerative diseases, notably age-related macular degeneration (AMD). Moreover, it has been shown that phosphorylation-mediated inactivation of PTEN (phosphatase and tensin homolog) in RPE is closely linked to AMD-like retinal degeneration in mice Ill. In this study, we used AMD mouse models, in which chemokine (C-C motif) ligand 2 (Ccl2) or chemokine (C-C motif) receptor 2 (Ccr2) were genetically ablated, to examine mechanisms linking reactive oxygen species (ROS) to phosphorylation/inactivation of PTEN in RPE. We found that ROS levels were increased in these RPE cells in association with phosphorylation/inactivation of PTEN. Both PTEN phosphorylation/inactivation and consequent Akt activation in the RPE of AMD model mice were inhibited by antioxidant treatment, indicating a functional role for elevated intracellular ROS. We further discovered that PTEN phosphorylation in oxidatively stressed RPE was repressed by a phosphoinositide 3-kinase (PI3K) inhibitor, but not by an Akt inhibitor. Taken together, these results suggest that ROS-activated PI3K potentiates AMD-related RPE pathogenesis through phosphorylation/inactivation of PTEN. Crown Copyright (C) 2011 Published by Elsevier Inc. All rights reserved.
C1 [Lee, Eun Jung; Kim, Namsuk; Kang, Kyung Hwa; Kim, Jin Woo] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea.
   [Kang, Kyung Hwa; Kim, Jin Woo] Korea Adv Inst Sci & Technol, KAIST Inst BioCentury, Taejon 305701, South Korea.
C3 Korea Advanced Institute of Science & Technology (KAIST); Korea Advanced
   Institute of Science & Technology (KAIST)
RP Kang, KH (通讯作者)，Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea.
EM kyunghwa70@kaist.ac.kr; jinwookim@kaist.ac.kr
RI KIM, JIN WOO/C-1655-2011
OI KIM, JIN WOO/0000-0003-0767-1918; KIM, Namsuk/0000-0001-5043-0293
FU Ministry of Health, Welfare and Family Affairs [A084337]
FX This work was supported by a grant from the Korean Healthcare Technology
   R&D Project, Ministry of Health, Welfare and Family Affairs (A084337).
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NR 34
TC 13
Z9 14
U1 0
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 OCT 22
PY 2011
VL 414
IS 2
BP 384
EP 389
DI 10.1016/j.bbrc.2011.09.083
PG 6
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 839YG
UT WOS:000296404800020
PM 21964287
DA 2022-11-30
ER

PT J
AU Lukason, M
   DuFresne, E
   Rubin, H
   Pechan, P
   Li, QH
   Kim, I
   Kiss, S
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   Collins, M
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   Hauswirth, W
   MacLachlan, T
   Wadsworth, S
   Scaria, A
AF Lukason, Michael
   DuFresne, Elizabeth
   Rubin, Hillard
   Pechan, Peter
   Li, Qiuhong
   Kim, Ivana
   Kiss, Szilard
   Flaxel, Christina
   Collins, Margaret
   Miller, Joan
   Hauswirth, William
   MacLachlan, Timothy
   Wadsworth, Samuel
   Scaria, Abraham
TI Inhibition of Choroidal Neovascularization in a Nonhuman Primate Model
   by Intravitreal Administration of an AAV2 Vector Expressing a Novel
   Anti-VEGF Molecule
SO MOLECULAR THERAPY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; PHASE-I TRIAL; LEBERS CONGENITAL AMAUROSIS;
   GENE-THERAPY; MACULAR DEGENERATION; RETINAL NEOVASCULARIZATION;
   PARKINSONS-DISEASE; OPEN-LABEL; SAFETY; TOLERABILITY
AB Inhibition of vascular endothelial growth factor (VEGF) for the management of the pathological ocular neovascularization associated with diseases such as neovascular age-related macular degeneration is a proven paradigm; however, monthly intravitreal injections are required for optimal treatment. We have previously shown that a novel, secreted anti-VEGF molecule sFLT01 delivered by intravitreal injection of an AAV2 vector (AAV2-sFLT01) gives persistent expression and is efficacious in a murine model of retinal neovascularization. In the present study, we investigate transduction and efficacy of an intravitreally administered AAV2-sFLT01 in a nonhuman primate (NHP) model of choroidal neovascularization (CNV). A dose-dependent and persistent expression of sFLT01 was observed by collecting samples of aqueous humor at different time points over 5 months. The location of transduction as elucidated by in situ hybridization was in the transitional epithelial cells of the pars plana and in retinal ganglion cells. AAV2-sFLT01 was able to effectively inhibit laser-induced CNV in a dose-dependent manner as determined by comparing the number of leaking CNV lesions in the treated versus control eyes using fluorescein angiography. Our data suggest that intravitreal delivery of AAV2-sFLT01 may be an effective long-term treatment for diseases caused by ocular neovascularization.
C1 [Lukason, Michael; DuFresne, Elizabeth; Rubin, Hillard; Pechan, Peter; MacLachlan, Timothy; Wadsworth, Samuel; Scaria, Abraham] Genzyme Corp, Framingham, MA 01701 USA.
   [Li, Qiuhong; Hauswirth, William] Univ Florida, Dept Ophthalmol, Gainesville, FL USA.
   [Kim, Ivana; Kiss, Szilard; Miller, Joan] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA.
   [Flaxel, Christina] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA.
   [Collins, Margaret] Charles River Labs Preclin Serv Nevada, Reno, NV USA.
C3 Sanofi-Aventis; Genzyme Corporation; State University System of Florida;
   University of Florida; Harvard University; Harvard Medical School;
   Massachusetts Eye & Ear Infirmary; Oregon Health & Science University
RP Scaria, A (通讯作者)，Genzyme Corp, 49 New York Ave, Framingham, MA 01701 USA.
EM abraham.scaria@genzyme.com
OI hauswirth, william/0000-0002-3244-4947; Kiss,
   Szilard/0000-0003-3433-8432; Kim, Ivana/0000-0003-0310-6129; Miller,
   Joan/0000-0003-2046-3996; Pechan, Peter/0000-0001-9663-8743
FU NATIONAL EYE INSTITUTE [P30EY021721] Funding Source: NIH RePORTER; NEI
   NIH HHS [P30 EY021721] Funding Source: Medline
CR Acland GM, 2001, NAT GENET, V28, P92, DOI 10.1038/ng0501-92
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NR 20
TC 61
Z9 70
U1 0
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD FEB
PY 2011
VL 19
IS 2
BP 260
EP 265
DI 10.1038/mt.2010.230
PG 6
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 715WM
UT WOS:000286923000009
PM 20978476
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Koizumi, H
   Iida, T
   Saito, M
   Nagayama, D
   Maruko, I
AF Koizumi, Hideki
   Iida, Tomohiro
   Saito, Masaaki
   Nagayama, Dai
   Maruko, Ichiro
TI Choroidal circulatory disturbances associated with retinal angiomatous
   proliferation on indocyanine green angiography
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE retinal angiomatous proliferation (RAP); age-related macular
   degeneration (ARMD); indocyanine green angiography; choroidal perfusion
ID NEOVASCULARIZATION
AB Purpose To investigate the association between choroidal perfusion and retinal angiomatous proliferation (RAP).
   Methods We performed indocyanine green angiography (ICGA) on 26 eyes of 13 consecutive patients with RAP, and 17 eyes of 17 age-matched controls without age-related macular degeneration. In eyes with RAP and concurrent pigment epithelial detachments (PEDs), we evaluated ICGA images obtained after the PEDs resolved following treatment. Of the 26 eyes in the study group, five eyes with stage 3 RAP or a disciform scar and two eyes that underwent photodynamic therapy were excluded from further evaluation, leaving 19 eyes (11 eyes with stage 1 or 2 RAP and eight fellow eyes without RAP).
   Results Early decreased choroidal filling (EDCF) was observed in nine (81.8%) of 11 eyes with RAP and five (62.5%) of eight fellow eyes without RAP. Late decreased choroidal filling (LDCF) occurred in nine (81.8%) of 11 eyes with RAP and four (50%) of eight fellow eyes without RAP. The incidence of EDCF and LDCF was significantly higher in eyes with RAP than in the control eyes (p < 0.05, p < 0.01, respectively).
   Conclusions Persistent decreased choroidal filling is common in early-stage RAP. Clinicians should be aware of this, especially when considering treatment.
C1 [Koizumi, Hideki; Iida, Tomohiro; Saito, Masaaki; Nagayama, Dai; Maruko, Ichiro] Fukushima Med Univ, Sch Med, Dept Ophthalmol, Fukushima 9601295, Japan.
   [Koizumi, Hideki] Kyoto Prefectural Univ Med, Dept Ophthalmol, Kyoto, Japan.
C3 Fukushima Medical University; Kyoto Prefectural University of Medicine
RP Iida, T (通讯作者)，Fukushima Med Univ, Sch Med, Dept Ophthalmol, 1 Hikarigaoka, Fukushima 9601295, Japan.
EM iidat@fmu.ac.jp
RI Saito, Masaaki/ABI-2783-2020; Maruko, Ichiro/AFP-1311-2022
OI Saito, Masaaki/0000-0003-1494-6350; Maruko, Ichiro/0000-0001-5647-6372
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NR 18
TC 29
Z9 29
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 APR
PY 2008
VL 246
IS 4
BP 515
EP 520
DI 10.1007/s00417-007-0705-3
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 277XV
UT WOS:000254248900006
PM 17972093
DA 2022-11-30
ER

PT J
AU Noda, K
   Miyahara, S
   Nakazawa, T
   Almulki, L
   Nakao, S
   Hisatomi, T
   She, H
   Thomas, KL
   Garland, RC
   Miller, JW
   Gragoudas, ES
   Kawai, Y
   Mashima, Y
   Hafezi-Moghadam, A
AF Noda, Kousuke
   Miyahara, Shinsuke
   Nakazawa, Torn
   Almulki, Lama
   Nakao, Shintaro
   Hisatomi, Toshio
   She, Haicheng
   Thomas, Kennard L.
   Garland, Rebecca C.
   Miller, Joan W.
   Gragoudas, Evangelos S.
   Kawai, Yosuke
   Mashima, Yukihiko
   Hafezi-Moghadam, Ali
TI Inhibition of vascular adhesion protein-1 suppresses endotoxin-induced
   uveifs
SO FASEB JOURNAL
LA English
DT Article
DE semicarbazide-sensitize amine oxidase; ocular inflammation; leukocyte
   recruitment
ID SENSITIVE AMINE OXIDASE; NECROSIS-FACTOR-ALPHA; IN-VIVO EVALUATION;
   INDUCED UVEITIS; P-SELECTIN; RETINAL MICROCIRCULATION; ENDOTHELIAL
   INTERACTIONS; OCULAR INFLAMMATION; MONOAMINE-OXIDASE; LEUKOCYTE BINDING
AB Inflammatory leukocyte accumulation is a common feature of major ocular diseases, such as uveitis, diabetic retinopathy, and age-related macular degeneration. Vascular adhesion protein-1 (VAP-1), a cell surface and soluble molecule that possesses semicarbazide-sensitive amine oxidase (SSAO) activity, is involved in leukocyte recruitment. However, the expression of VAP-1 in the eye and its contribution to ocular inflammation are unknown. Here, we investigated the role of VAP-1 in an established model of ocular inflammation, the endotoxin-induced uveitis (EIU), using a novel and specific inhibitor. Our inhibitor has a half-maximal inhibitory concentration (IC50) of 0.007 mu M against human and 0.008 mu M against rat SSAO, while its IC50 against the functionally related monoamine oxidase (MAO) -A and MAO-B is > 10 mu M. In the retina, VAP-1 was exclusively expressed in the vasculature, and its expression level was elevated during EIU. VAP-1 inhibition in EIU animals significantly suppressed leukocyte recruitment to the anterior chamber, vitreous, and retina, as well as retinal endothelial P-selectin expression. Our data suggest an important role for VAP-1 in the recruitment of leukocytes to the immune-privileged ocular tissues during acute inflammation. VAP-1 inhibition may become a novel strategy in the treatment of ocular inflammatory diseases.
C1 [Noda, Kousuke; Miyahara, Shinsuke; Nakazawa, Torn; Almulki, Lama; Nakao, Shintaro; Hisatomi, Toshio; She, Haicheng; Thomas, Kennard L.; Garland, Rebecca C.; Miller, Joan W.; Gragoudas, Evangelos S.; Hafezi-Moghadam, Ali] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA.
   [Kawai, Yosuke; Mashima, Yukihiko] Harvard Univ, Sch Med, Boston, MA 02115 USA.
C3 Harvard University; Massachusetts Eye & Ear Infirmary; Harvard
   University; Harvard Medical School
RP Hafezi-Moghadam, A (通讯作者)，Angiogenesis Lab, 325 Cambridge St,3rd Floor, Boston, MA 02114 USA.
EM ahm@meei.harvard.edu
OI Hafezi-Moghadam, Ali/0000-0002-5336-0697; Hisatomi,
   Toshio/0000-0003-2552-9595; Miller, Joan/0000-0003-2046-3996
FU NATIONAL EYE INSTITUTE [P30EY014104] Funding Source: NIH RePORTER;
   NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [K08AI050775]
   Funding Source: NIH RePORTER; NEI NIH HHS [EY14104] Funding Source:
   Medline; NIAID NIH HHS [AI-050775] Funding Source: Medline
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NR 43
TC 46
Z9 60
U1 2
U2 4
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 APR
PY 2008
VL 22
IS 4
BP 1094
EP 1103
DI 10.1096/fj.07-9377com
PG 10
WC Biochemistry & Molecular Biology; Biology; Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
   Topics; Cell Biology
GA 282PZ
UT WOS:000254581000015
PM 18032635
DA 2022-11-30
ER

PT J
AU Bando, H
   Shadrach, KG
   Rayborn, ME
   Crabb, JW
   Hollyfield, JG
AF Bando, Hajime
   Shadrach, Karen G.
   Rayborn, Mary E.
   Crabb, John W.
   Hollyfield, Joe G.
TI Clathrin and adaptin accumulation in drusen, Bruch's membrane and
   choroid in AMD and non-AMD donor eyes
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE adaptin; age-related macular degeneration (AMD); Bruch's membrane;
   choroid; clathrin; drusen; retinal pigment epithelium (RPE)
ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; RISK-FACTORS;
   PATHOGENESIS; GENES
AB Clathrin was identified in a recent proteomic analysis of Bruch's membrane from age-related macular degeneration (AMD) donor eyes. The present study was conducted to determine the localization of clathrin in AMD tissues and to compare this distribution and relative content with that in non-AMD control tissues. The distribution of adaptin, which is functionally linked to clathrin, was also evaluated. Human eyes were from donors between 66 and 94 years of age; 13 eyes were from donors with AMD and 13 from non-AMD donors. Bruch's membrane and choroid from the macula of each donor eye were prepared for immunohistochemistry and Western blotting. Differences in immunoreactivity were quantitated. Drusen, Bruch's membrane and choroid from AMD tissues showed greater immunoreactivity for clathrin and adaptin than did non-AMD tissues. Western blots also showed more intense clathrin and adaptin immunoreactivity in AMD tissues than were present in non-AMD samples. This study suggests that accumulation of clathrin and adaptin in drusen, Bruch's membrane and choroid may reflect a higher rate of clathrin mediated endocytosis in AMD tissues. Alternatively, the accumulation of these proteins in these extracellular compartments may reflect a higher susceptibility to oxidative damage. (c) 2006 Elsevier Ltd. All rights reserved.
C1 Case Western Reserve Univ, Cleveland Clin Fdn, Lerner Coll Med, Cole Eye Inst,Dept Ophthalmol, Cleveland, OH 44195 USA.
C3 Case Western Reserve University; Cleveland Clinic Foundation
RP Hollyfield, JG (通讯作者)，Case Western Reserve Univ, Cleveland Clin Fdn, Lerner Coll Med, Cole Eye Inst,Dept Ophthalmol, 9500 Euclid Ave, Cleveland, OH 44195 USA.
EM hollyj@ccf.org
FU NATIONAL EYE INSTITUTE [R01EY014239, R01EY014240, R56EY014240] Funding
   Source: NIH RePORTER; NEI NIH HHS [R01 EY014239, EY014240, R01 EY014240,
   EY014239] Funding Source: Medline
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NR 37
TC 10
Z9 10
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD JAN
PY 2007
VL 84
IS 1
BP 135
EP 142
DI 10.1016/j.exer.2006.09.008
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 123JP
UT WOS:000243292500017
PM 17097084
DA 2022-11-30
ER

PT J
AU Ferrington, DA
   Tran, TN
   Lew, KL
   Van Remmen, H
   Gregerson, DS
AF Ferrington, Deborah A.
   Tran, Tina N.
   Lew, Kathleen L.
   Remmen, Holly Van
   Gregerson, Dale S.
TI Different death stimuli evoke apoptosis via multiple pathways in retinal
   pigment epithelial cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE apoptosis; retinal pigment epithelial cells; oxidation; cytotoxic T
   lymphocytes; fas
ID MANGANESE-SUPEROXIDE-DISMUTASE; MACULAR DEGENERATION; IN-VITRO;
   CYTOMEGALOVIRUS RETINITIS; DILATED CARDIOMYOPATHY; BETA-GALACTOSIDASE;
   NEONATAL LETHALITY; HYDROGEN-PEROXIDE; OXIDATIVE DAMAGE; BINDING-PROTEIN
AB Loss of retinal pigment epithelial (RPE) cells via apoptosis plays a prominent role in several retinal degenerative diseases, such as age-related macular degeneration, and with light damage. Strategies for preservation of vision that would interrupt the apoptotic cascade require understanding the molecular events associated with apoptosis. This study investigated the susceptibility of RPE to caspase-dependent and -independent apoptotic pathways when challenged with different stimuli, including oxidants, anti-Fas antibody, and activated cytotoxic T lymphocytes (CTLs). These experiments used novel RPE cell lines developed from wildtype and heterozygous mice with reduced levels of either Mn superoxide dismutatse (SOD) or CuZnSOD. Peroxide and 4-hydroxynonenal induced apoptosis through both caspase-independent and -dependent pathways, respectively. With both oxidants, translocation of apoptosis inducing factor into the nucleus was observed. Cells containing reduced levels of CuZnSOD were the most susceptible to oxidant-induced cell death. Targeted killing by CTLs and activation of the Fas death receptor induced caspase-dependent apoptosis. These results show stimulus-specific activation of either the caspase-dependent or -independent pathway. Since cultured RPE express the protein components required for different apoptotic pathways, they provide a good model system for studying molecular events associated with multiple signals that lead to cell death. (c) 2006 Elsevier Ltd. All rights reserved.
C1 Univ Minnesota, Dept Ophthalmol, Minneapolis, MN 55455 USA.
   Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA.
   Univ Texas, Hlth Sci Ctr, Barshop Ctr Longev Studies, San Antonio, TX 78284 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities;
   University of Texas System; University of Texas Health San Antonio;
   University of Texas System; University of Texas Health San Antonio
RP Ferrington, DA (通讯作者)，Univ Minnesota, Dept Ophthalmol, 380 Lions Res Bldg,2001 6th St SE, Minneapolis, MN 55455 USA.
EM ferri013@umn.edu
OI Ferrington, Deborah/0000-0003-2561-7464; Gregerson,
   Dale/0000-0001-5769-796X
FU NEI NIH HHS [EY 011542, EY 014176, P30 EY 11374, T32 EY 07133] Funding
   Source: Medline; NATIONAL EYE INSTITUTE [R01EY011542, P30EY011374,
   T32EY007133, R03EY014176] Funding Source: NIH RePORTER
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NR 59
TC 31
Z9 35
U1 0
U2 7
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD SEP
PY 2006
VL 83
IS 3
BP 638
EP 650
DI 10.1016/j.exer.2006.03.003
PG 13
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 073OD
UT WOS:000239751600022
PM 16682026
DA 2022-11-30
ER

PT J
AU Wang, MC
   Tsao, R
   Zhang, SF
   Dong, ZM
   Yang, R
   Gong, JH
   Pei, YX
AF Wang, Mingchen
   Tsao, Rong
   Zhang, Shanfeng
   Dong, Ziming
   Yang, Raymond
   Gong, Jianhua
   Pei, Yingxin
TI Antioxidant activity, mutagenicity/anti-mutagenicity, and
   clastogenicity/anti-clastogenicity of lutein from marigold flowers
SO FOOD AND CHEMICAL TOXICOLOGY
LA English
DT Article
DE carotenoids; lutein; Ames test; chromosome aberration test;
   mutagenicity; anti-mutagenicity; clastogenicity; anti-clastogenicity
ID BETA-CAROTENE; LUNG-CANCER; ANTIMUTAGENIC ACTIVITY; TAGETES-ERECTA;
   DAMAGE; ACID; XANTHOPHYLLS; EXTRACT; RISK
AB High dietary intake of lutein has been associated with risk reduction of many chronic diseases, including age-related macular degeneration (AMD), cancer, and cardiovascular diseases. Lutein in food is generally regarded as safe. However, information on the toxicological and beneficial effect of lutein at higher doses is limited. In this study, large amount of lutein was extracted and purified from marigold flower (Tagetes erecta L.). The antioxidant activity of lutein was examined by using the photochemiluminescence (PCL) assay and the P-carotene-linoleic acid model system (P-CLAMS). Lutein showed a greater antioxidant activity than the other two common carotenoids, P-carotene and lycopene. The mutagenicity and anti-mutagenicity of lutein at 334, 668 and 1335 mu g/plate were examined using the standard Ames test in the presence and absence of S9 mix. Lutein was not only found to be non-mutagenic at all doses, but it showed an anti-mutagenic effect in a dose-dependent manner. Similar results were found in a chromosome aberration test using Chinese hamster ovary cells for the evaluation of clastogenicity and anti-clastogenicity of lutein at 66.8, 133.5 and 267.0 mg/L. Our findings provided scientific evidence for the safe use and health beneficial effects of lutein. (c) 2006 Elsevier Ltd. All rights reserved.
C1 Agr & Agri Food Canada, Food Res Program, Guelph, ON N1G 5C9, Canada.
   Zhengzhou Univ, Coll Med Sci, Dept Biochem & Mol Biol, Zhengzhou 450052, Henan Province, Peoples R China.
   Zhengzhou Univ, Coll Publ Hlth Sci, Dept Human Nutr, Zhengzhou 450052, Henan Province, Peoples R China.
C3 Agriculture & Agri Food Canada; Zhengzhou University; Zhengzhou
   University
RP Tsao, R (通讯作者)，Agr & Agri Food Canada, Food Res Program, 93 Stone Rd W, Guelph, ON N1G 5C9, Canada.
EM caor@agr.gc.ca
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   [No title captured]
NR 33
TC 77
Z9 92
U1 0
U2 23
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-6915
EI 1873-6351
J9 FOOD CHEM TOXICOL
JI Food Chem. Toxicol.
PD SEP
PY 2006
VL 44
IS 9
BP 1522
EP 1529
DI 10.1016/j.fct.2006.04.005
PG 8
WC Food Science & Technology; Toxicology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Food Science & Technology; Toxicology
GA 080KS
UT WOS:000240247100010
PM 16757077
DA 2022-11-30
ER

PT J
AU Rudolf, M
   Winkler, B
   Aherrahou, Z
   Doehring, LC
   Kaczmarek, P
   Schmidt-Erfurth, U
AF Rudolf, M
   Winkler, B
   Aherrahou, Z
   Doehring, LC
   Kaczmarek, P
   Schmidt-Erfurth, U
TI Increased expression of vascular endothelial growth factor associated
   with accumulation of lipids in Bruch's membrane of LDL receptor knockout
   mice
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; AGE; PATHOGENESIS;
   MODEL; VEGF
AB Aim: To investigate the pathogenesis of age related macular degeneration (ARM) with respect to lipid accumulation within Bruch's membrane (BrM) in a knockout model with low density lipoprotein (LDL) receptor deficiency.
   Methods: LDL receptor deficient mice and C57BL/6 controls were fed a standard diet or a high fat (HF) diet. Plasma total cholesterol (pTC) was determined. Eyes were examined by transmission electron microscopy. Immunohistochemical staining for VEGF was performed.
   Results: pTC were highest in LDL receptor deficient mice after HF diet and elevated after standard diet compared to controls with and without HF diet. While BrM of controls did not exhibit any visible changes, membrane bound translucent particles were seen in all BrM of knockout mice. The amount of these particles was substantially increased and membranes were thickened after HF diet. VEGF staining was positive in knockout mice only and was located in retinal pigment epithelial cells, the outer plexiform layer, and photoreceptor inner segments. Most intensive VEGF expression was documented after HF diet.
   Conclusion: LDL receptor deficient mice exhibit an accumulation of lipid particles in BrM which is further increased after fat intake. VEGF expression is found in the outer retinal layers of LDL receptor deficient mice and appears to correlate with the amount of lipid particles present in BrM.
C1 Univ Schleswig Holstein, Dept Ophthalmol, D-24105 Kiel, Germany.
   Med Univ Lubeck, Dept Med, Atherosclerot Study Grp, D-23538 Lubeck, Germany.
   Univ Vienna, Dept Ophthalmol, Vienna, Austria.
C3 University of Kiel; Schleswig Holstein University Hospital; University
   of Lubeck; University of Vienna
RP Rudolf, M (通讯作者)，Univ Schleswig Holstein, Dept Ophthalmol, Campus Kiel,Hegewisch Str 2, D-24105 Kiel, Germany.
EM mirudolf@aol.com
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NR 20
TC 46
Z9 52
U1 0
U2 4
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 DEC
PY 2005
VL 89
IS 12
BP 1627
EP 1630
DI 10.1136/bjo.2005.071183
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 985HR
UT WOS:000233368700020
PM 16299144
OA Green Published, Bronze
DA 2022-11-30
ER

PT J
AU Du, H
   Huang, ZX
   Zhou, X
   Kuang, XL
   Long, CD
   Tang, H
   Zeng, JS
   Huang, H
   Liu, HJ
   Zhu, BB
   Fu, LC
   Hu, K
   Lin, SB
   Wang, H
   Zhang, QJ
   Yan, JH
   Shen, HX
AF Du, Han
   Huang, Zixin
   Zhou, Xin
   Kuang, Xielan
   Long, Chongde
   Tang, Han
   Zeng, Jingshu
   Huang, Hao
   Liu, Huijun
   Zhu, Binbin
   Fu, Licheng
   Hu, Ke
   Lin, ShuiBin
   Wang, Hua
   Zhang, Qingjiong
   Yan, Jianhua
   Shen, Huangxuan
TI Oxidative stress-induced lncRNA CYLD-AS1 promotes RPE inflammation via
   Nrf2/miR-134-5p/NF-kappa B signaling pathway
SO FASEB JOURNAL
LA English
DT Article
DE AMD; inflammation; lncRNA; miRNA; oxidative stress; RPE
ID DAMAGE; DEGENERATION
AB Oxidative stress-induced damage to and dysfunction of retinal pigment epithelium (RPE) cells are important pathogenetic factors of age-related macular degeneration (AMD); however, the underlying molecular mechanism is not fully understood. Long noncoding RNAs (lncRNAs) have important roles in various biological processes. In this study, using an oxidative damage model in RPE cells, we identified a novel oxidation-related lncRNA named CYLD-AS1. We further revealed that the expression of CYLD-AS1 was increased in RPEs during oxidative stress. Depletion of CYLD-AS1 promoted cell proliferation and mitochondrial function and protected RPE cells against hydrogen peroxide (H2O2)-induced damage. Mechanistically, CYLD-AS1 also regulated the expression of NRF2, which is related to oxidative stress, and NF-kappa B signaling pathway members, which are related to inflammation. Remarkably, these two signaling pathways were mediated by the CYLD-AS1 interactor miR-134-5p. Moreover, exosomes secreted by CYLD-AS1 knockdown RPE cells had a lower proinflammatory effect than those secreted by control cells. In summary, our study revealed that CYLD-AS1 affects the oxidative stress-related and inflammatory functions of RPE cells by sponging miR-134-5p to mediate NRF2/NF-kappa B signaling pathway activity, suggesting that targeting CYLD-AS1 could be a promising strategy for the treatment of AMD and related diseases.
C1 [Du, Han; Huang, Zixin; Zhou, Xin; Kuang, Xielan; Long, Chongde; Tang, Han; Zeng, Jingshu; Huang, Hao; Liu, Huijun; Zhu, Binbin; Fu, Licheng; Hu, Ke; Zhang, Qingjiong; Yan, Jianhua; Shen, Huangxuan] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, 54 Xianlie Rd, Guangzhou 510060, Peoples R China.
   [Zhou, Xin] Univ Florida, Dept Mol Genet & Microbiol, Coll Med, Gainesville, FL USA.
   [Kuang, Xielan; Shen, Huangxuan] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Biobank Eye, Guangzhou, Peoples R China.
   [Huang, Hao] Guangzhou Med Univ, Dept Ophthalmol, Affiliated Hosp 1, Guangzhou, Peoples R China.
   [Liu, Huijun] Wuhan Univ Sci & Technol, Tianyou Hosp, Dept Ophthalmol, Wuhan, Peoples R China.
   [Lin, ShuiBin] Sun Yat Sen Univ, Affiliated Hosp 1, Ctr Translat Med, Precis Med Inst, Guangzhou, Peoples R China.
   [Wang, Hua] Southern Med Univ, Zhujiang Hosp, Dept Intens Care, Guangzhou, Peoples R China.
C3 Sun Yat Sen University; State University System of Florida; University
   of Florida; Sun Yat Sen University; Guangzhou Medical University; Wuhan
   University of Science & Technology; Sun Yat Sen University; Southern
   Medical University - China
RP Yan, JH; Shen, HX (通讯作者)，Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, 54 Xianlie Rd, Guangzhou 510060, Peoples R China.
EM yanjh2011@126.com; shenhx@mail.sysu.edu.cn
FU National Natural Science Foundation of China [81670874, 81670885];
   Natural Science Foundation of Guangdong Province of China
   [2020A1515010144, 2021A1515010513, 2022A1515012442]; Fundamental
   Research Funds of the State Key Laboratory of Ophthalmology; Open
   Research Funds of the State Key Laboratory of Ophthalmology
FX The work was supported by the National Natural Science Foundation of
   China (81670874 and 81670885), Natural Science Foundation of Guangdong
   Province of China (Nos. 2020A1515010144, 2021A1515010513, and
   2022A1515012442), and the Fundamental Research Funds of the State Key
   Laboratory of Ophthalmology (No. N/A) and the Open Research Funds of the
   State Key Laboratory of Ophthalmology (No. N/A).
CR Ambati J, 2003, NAT MED, V9, P1390, DOI 10.1038/nm950
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NR 44
TC 0
Z9 0
U1 2
U2 2
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0892-6638
EI 1530-6860
J9 FASEB J
JI Faseb J.
PD OCT
PY 2022
VL 36
IS 10
AR e22577
DI 10.1096/fj.202200887R
PG 17
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 4W1SF
UT WOS:000859945000001
PM 36165267
DA 2022-11-30
ER

PT J
AU Peng, MJ
   Zhou, XZ
   Yao, F
   Li, HB
   Song, WT
   Xiong, SQ
   Xia, XB
AF Peng, Manjuan
   Zhou, Xuezhi
   Yao, Fei
   Li, Haibo
   Song, Weitao
   Xiong, Siqi
   Xia, Xiaobo
TI (-)-Epicatechin Provides Neuroprotection in Sodium Iodate-Induced
   Retinal Degeneration
SO FRONTIERS IN MEDICINE
LA English
DT Article
DE age-related macular degeneration; (-)-epicatechin; mitochondrial
   dynamics; mitochondrial quality control; TMEM97; amyloid beta
ID MACULAR DEGENERATION; RAT RETINA; EPICATECHIN; RECEPTOR; DAMAGE;
   BIOGENESIS; INDICATORS; EPITHELIUM; DISEASE; MODELS
AB Oxidative stress, mitochondrial impairment, and pathological amyloid beta (A beta) deposition are involved in the pathogenesis of dry age-related macular degeneration (AMD). The natural flavonoid (-)-epicatechin (EC) is known to be an antioxidant and neuroprotective compound. Whether EC plays a therapeutic role in AMD is unknown. In this work, we aimed to assess the efficacy and molecular mechanisms of EC against sodium iodate (NaIO3)-induced retinal degeneration in C57BL/6 mice via bioinformatic, morphological, and functional methods. We demonstrated that EC had no toxic effects on the retina and could ameliorate retinal deformation and thinning. EC treatment prevented outer retinal degeneration, reduced drusen-like deposits, increased b-wave amplitude in electroretinography, blocked retinal gliosis, and increased the number and quality of mitochondria. Importantly, EC increased the protein expression of OPA1 and decreased the expression of PINK1, indicating the role of EC in mitochondrial fusion that impaired by NaIO3. Moreover, EC downregulated APP and TMEM97 levels, upregulated PGRMC1 levels, and reduced subretinal A beta accumulation. This study illustrated that EC, which may become a promising therapeutic strategy for AMD, prevented NaIO3-induced retinal degeneration, and this improvement may be associated with the mitochondrial quality control and the TMEM97/PGRMC1/A beta signaling pathway.
C1 [Peng, Manjuan; Zhou, Xuezhi; Yao, Fei; Li, Haibo; Song, Weitao; Xiong, Siqi; Xia, Xiaobo] Cent South Univ, Xiangya Hosp, Eye Ctr, Changsha, Peoples R China.
   [Peng, Manjuan; Zhou, Xuezhi; Yao, Fei; Li, Haibo; Song, Weitao; Xiong, Siqi; Xia, Xiaobo] Cent South Univ, Xiangya Hosp, Hunan Key Lab Ophthalmol, Changsha, Peoples R China.
   [Peng, Manjuan; Zhou, Xuezhi; Yao, Fei; Li, Haibo; Song, Weitao; Xiong, Siqi; Xia, Xiaobo] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha, Peoples R China.
C3 Central South University; Central South University; Central South
   University
RP Xiong, SQ; Xia, XB (通讯作者)，Cent South Univ, Xiangya Hosp, Eye Ctr, Changsha, Peoples R China.; Xiong, SQ; Xia, XB (通讯作者)，Cent South Univ, Xiangya Hosp, Hunan Key Lab Ophthalmol, Changsha, Peoples R China.; Xiong, SQ; Xia, XB (通讯作者)，Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha, Peoples R China.
EM petersage1221@126.com; xbxia21@csu.edu.cn
FU National Natural Science Foundation of China [81974134, 81670858,
   81974137, 82171058]; National Key Research and Development Program of
   China [2020YFC2008205]; Key R&D plan of Hunan Province of China
   [2020SK2076]
FX Funding This research was supported by grants from the National Natural
   Science Foundation of China (Nos. 81974134, 81670858, 81974137, and
   82171058), National Key Research and Development Program of China (No.
   2020YFC2008205), and Key R&D plan of Hunan Province of China (No.
   2020SK2076).
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NR 50
TC 0
Z9 0
U1 4
U2 4
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
EI 2296-858X
J9 FRONT MED-LAUSANNE
JI Front. Med.
PD JUN 27
PY 2022
VL 9
AR 879901
DI 10.3389/fmed.2022.879901
PG 13
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA 2T9YQ
UT WOS:000822822300001
PM 35833100
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Lopez-Cuenca, I
   Salobrar-Garcia, E
   Gil-Salgado, I
   Sanchez-Puebla, L
   Elvira-Hurtado, L
   Fernandez-Albarral, JA
   Ramirez-Torano, F
   Barabash, A
   de Frutos-Lucas, J
   Salazar, JJ
   Ramirez, JM
   Ramirez, AI
   de Hoz, R
AF Lopez-Cuenca, Ines
   Salobrar-Garcia, Elena
   Gil-Salgado, Ines
   Sanchez-Puebla, Lidia
   Elvira-Hurtado, Lorena
   Fernandez-Albarral, Jose A.
   Ramirez-Torano, Federico
   Barabash, Ana
   de Frutos-Lucas, Jaisalmer
   Salazar, Juan J.
   Ramirez, Jose M.
   Ramirez, Ana, I
   de Hoz, Rosa
TI Characterization of Retinal Drusen in Subjects at High Genetic Risk of
   Developing Sporadic Alzheimer's Disease: An Exploratory Analysis
SO JOURNAL OF PERSONALIZED MEDICINE
LA English
DT Article
DE Alzheimer's disease; ApoE epsilon 4; family history; hard drusen; OCT;
   retina; AMD; hypercholesterolemia; hypertension; diabetes mellitus;
   choroid
ID MACULAR DEGENERATION; APOLIPOPROTEIN-E; ATHEROSCLEROSIS; APOE; DEMENTIA
AB Having a family history (FH+) of Alzheimer's disease (AD) and being a carrier of at least one epsilon 4 allele of the ApoE gene are two of the main risk factors for the development of AD. AD and age-related macular degeneration (AMD) share one of the main risk factors, such as age, and characteristics including the presence of deposits (A beta plaques in AD and drusen in AMD); however, the role of apolipoprotein E isoforms in both pathologies is controversial. We analyzed and characterized retinal drusen by optical coherence tomography (OCT) in subjects, classifying them by their AD FH (FH- or FH+) and their allelic characterization of ApoE epsilon 4 (ApoE epsilon 4- or ApoE epsilon 4+) and considering cardiovascular risk factors (hypercholesterolemia, hypertension, and diabetes mellitus). In addition, we analyzed the choroidal thickness by OCT and the area of the foveal avascular zone with OCTA. We did not find a relationship between a family history of AD or any of the ApoE isoforms and the presence or absence of drusen. Subjects with drusen show choroidal thinning compared to patients without drusen, and thinning could trigger changes in choroidal perfusion that may give rise to the deposits that generate drusen.
C1 [Lopez-Cuenca, Ines; Salobrar-Garcia, Elena; Gil-Salgado, Ines; Sanchez-Puebla, Lidia; Elvira-Hurtado, Lorena; Fernandez-Albarral, Jose A.; Salazar, Juan J.; Ramirez, Jose M.; Ramirez, Ana, I; de Hoz, Rosa] Univ Complutense Madrid, Hlth Res Inst Hosp Clin San Carlos IdISSC, Ramon Castroviejo Inst Ophthalmol Res, Grp UCM 920105, Madrid 28040, Spain.
   [Salobrar-Garcia, Elena; Salazar, Juan J.; Ramirez, Ana, I; de Hoz, Rosa] Univ Complutense Madrid, Fac Opt & Optometry, Dept Immunol Ophthalmol & ENT, Madrid 28037, Spain.
   [Ramirez-Torano, Federico; de Frutos-Lucas, Jaisalmer] Tech Univ Madrid, Ctr Biomed Technol, Lab Cognit & Computat Neurosci, Madrid 28233, Spain.
   [Ramirez-Torano, Federico; de Frutos-Lucas, Jaisalmer] Univ Complutense Madrid, Dept Expt Psychol, Madrid 28223, Spain.
   [Barabash, Ana] IdISSC, Dept Endocrinol & Nutr, Madrid 28040, Spain.
   [Barabash, Ana] Carlos III Hlth Inst, Diabet & Associated Metab Dis Networking Biomed R, Madrid 28029, Spain.
   [Barabash, Ana] Univ Complutense Madrid, Sch Med, Dept Med 2, Madrid 28040, Spain.
   [de Frutos-Lucas, Jaisalmer] Edith Cowan Univ, Ctr Precis Hlth, Joondalup, WA 6027, Australia.
   [de Frutos-Lucas, Jaisalmer] Antonio Nebrija Univ, Fac Life & Nat Sci, Dept Psychol, Madrid 28015, Spain.
   [Ramirez, Jose M.] Univ Complutense Madrid, Sch Med, Dept Immunol Ophthalmol & ENT, Madrid 28040, Spain.
C3 Complutense University of Madrid; Complutense University of Madrid;
   Universidad Politecnica de Madrid; Complutense University of Madrid;
   Complutense University of Madrid; Edith Cowan University; Universidad
   Antonio de Nebrija; Complutense University of Madrid
RP de Hoz, R (通讯作者)，Univ Complutense Madrid, Hlth Res Inst Hosp Clin San Carlos IdISSC, Ramon Castroviejo Inst Ophthalmol Res, Grp UCM 920105, Madrid 28040, Spain.
EM inelopez@ucm.es; elenasalobrar@med.ucm.es; inegi101@ucm.es;
   lidsan02@ucm.es; marelvir@ucm.es; joseaf08@ucm.es; federami@ucm.es;
   ana.barabash@gmail.com; jaisamer.defrutos@ctb.upm.es;
   jjsalazar@med.ucm.es; ramirezs@med.ucm.es; airamirez@med.ucm.es;
   rdehoz@med.ucm.es
RI Barabash, Ana/AAD-2141-2020; Fernández-Albarral, Jose A./AAG-4357-2020;
   Ramirez, Jose M./L-6325-2014; Salazar, Juan J/L-6887-2014
OI Barabash, Ana/0000-0003-2383-1563; Fernández-Albarral, Jose
   A./0000-0003-0399-7996; Sanchez-Puebla Fernandez,
   Lidia/0000-0002-4430-8782; Ramirez, Jose M./0000-0002-5145-5094;
   Salazar, Juan J/0000-0001-5480-5902; De Hoz, Rosa/0000-0002-1581-087X;
   Ramirez, Ana I/0000-0002-2656-4723; GARCIA MARTIN, ELENA
   SALOBRAR/0000-0001-5939-5551
FU Ophthalmological Network OFTARED of the Institute of Health of Carlos
   III of the Spanish Ministry of Science and Innovation [RD16/0008/0005];
   Research Network RETIBRAIN of the Spanish Ministry of Science and
   Innovation [RED2018-102499-T]; Spanish Ministry of Economy and
   Competitiveness [PSI2015-68793-C3-1-R]; Complutense University of Madrid
   [CT42/18-CT43/18, CT82/20-CT83/20]; Spanish Ministry of Science,
   Innovation, and Universities [FPU17/01023]
FX This research was funded by the Ophthalmological Network OFTARED
   (RD16/0008/0005) of the Institute of Health of Carlos III of the Spanish
   Ministry of Science and Innovation; the Research Network RETIBRAIN
   (RED2018-102499-T) of the Spanish Ministry of Science and Innovation;
   and the Spanish Ministry of Economy and Competitiveness (Grant
   PSI2015-68793-C3-1-R). I.L.-C. is currently supported by a Predoctoral
   Fellowship (CT42/18-CT43/18) from the Complutense University of Madrid.
   J.A.F.-A. is currently supported by a Predoctoral Fellowship
   (FPU17/01023) from the Spanish Ministry of Science, Innovation, and
   Universities. L.S.-P. is currently supported by a Predoctoral Fellowship
   (CT82/20-CT83/20) from the Complutense University of Madrid. The sponsor
   or funding organization had no role in the design or conduct of this
   research. Approval date: 17 December 2018.
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NR 53
TC 0
Z9 0
U1 2
U2 2
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2075-4426
J9 J PERS MED
JI J. Pers. Med.
PD MAY
PY 2022
VL 12
IS 5
AR 847
DI 10.3390/jpm12050847
PG 15
WC Health Care Sciences & Services; Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Health Care Sciences & Services; General & Internal Medicine
GA 1O4HP
UT WOS:000801295900001
PM 35629270
OA gold, Green Published, Green Accepted
DA 2022-11-30
ER

PT J
AU Villarejo-Zori, B
   Jimenez-Loygorri, JI
   Zapata-Munoz, J
   Bell, K
   Boya, P
AF Villarejo-Zori, Beatriz
   Jimenez-Loygorri, Juan Ignacio
   Zapata-Munoz, Juan
   Bell, Katharina
   Boya, Patricia
TI New insights into the role of autophagy in retinal and eye diseases
SO MOLECULAR ASPECTS OF MEDICINE
LA English
DT Review
DE Autophagy; Retina; Glaucoma; Macular degeneration; Retinal dystrophies
ID PHOTORECEPTOR CELL-DEATH; MOUSE MODEL; PIGMENT EPITHELIUM; OXIDATIVE
   STRESS; MEDIATED AUTOPHAGY; VISION LOSS; DEGENERATION; AGE; MITOPHAGY;
   OPA1
AB Autophagy is a fundamental homeostatic pathway that mediates the degradation and recycling of intracellular components. It serves as a key quality control mechanism, especially in non-dividing cells such as neurons. Proteins, lipids, and even whole organelles are engulfed in autophagosomes and delivered to the lysosome for elimination. The retina is a light-sensitive tissue located in the back of the eye that detects and processes visual images. Vision is a highly demanding process, making the eye one of the most metabolically active tissues in the body and photoreceptors display glycolytic metabolism, even in the presence of oxygen. The retina and eye are also exposed to other stressors that can impair their function, including genetic mutations and age-associated changes. Autophagy, among other pathways, is therefore a key process for the preservation of retinal homeostasis. Here, we review the roles of both canonical and non-canonical autophagy in normal retinal function. We discuss the most recent studies investigating the participation of autophagy in eye diseases such as age-related macular degeneration, glaucoma, and diabetic retinopathy and its role protecting photoreceptors in several forms of retinal degeneration. Finally, we consider the therapeutic potential of strategies that target autophagy pathways to treat prevalent retinal and eye diseases.
C1 [Villarejo-Zori, Beatriz; Jimenez-Loygorri, Juan Ignacio; Zapata-Munoz, Juan; Boya, Patricia] CSIC, Margarita Salas Ctr Biol Res, Dept Cellular & Mol Biol, Ramiro de Maetzu 9, Comm Madrid 28040, Spain.
   [Bell, Katharina] Singapore Eye Res Inst, Singapore, Singapore.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); National
   University of Singapore; Singapore National Eye Center
RP Boya, P (通讯作者)，CSIC, Margarita Salas Ctr Biol Res, Dept Cellular & Mol Biol, Ramiro de Maetzu 9, Comm Madrid 28040, Spain.
EM patricia.boya@csic.es
RI Boya, Patricia/P-8345-2019
OI Boya, Patricia/0000-0003-3045-951X; Jimenez-Loygorri, Juan
   Ignacio/0000-0002-3065-9952; Zapata Munoz, Juan/0000-0003-4747-920X
FU Spain's Ministerio Ciencia e Innovacion, Agencia Estatal de
   Investigacion (AEI) [PGC2018-098557-B-I00]; Fondo Europeo de Desarrollo
   Regional (FEDER); European Union [765912]; Fundacion Tatiana Perez de
   Guzman el Bueno Proyectos en Neurociencia; Redes de Bio-Medicina de la
   Comunidad de Madrid [BMD-3813]; FPI (Ministerio Ciencia e Innovacion);
   FPU (Ministerio de Universidades)
FX Research in the P.B. lab is supported by funding (PGC2018-098557-B-I00)
   from Spain's Ministerio Ciencia e Innovacion, Agencia Estatal de
   Investigacion (AEI) , the Fondo Europeo de Desarrollo Regional (FEDER) ,
   the European Union's Horizon 2020 research and innovation program (grant
   agreement No 765912) , the Fundacion Tatiana Perez de Guzman el Bueno
   Proyectos en Neurociencia 2018, and Redes de Bio-Medicina de la
   Comunidad de Madrid (BMD-3813) . JIJL and JZPM are recipients of FPI
   (Ministerio Ciencia e Innovacion) and FPU (Ministerio de Universidades)
   fellowships, respectively. We thank O. Howard for English-language
   editing.
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NR 194
TC 6
Z9 6
U1 4
U2 7
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 DEC
PY 2021
VL 82
AR 101038
DI 10.1016/j.mam.2021.101038
EA DEC 2021
PG 18
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Research & Experimental Medicine
GA XO7EE
UT WOS:000730343200006
PM 34620506
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Holan, V
   Palacka, K
   Hermankova, B
AF Holan, Vladimir
   Palacka, Katerina
   Hermankova, Barbora
TI Mesenchymal Stem Cell-Based Therapy for Retinal Degenerative Diseases:
   Experimental Models and Clinical Trials
SO CELLS
LA English
DT Review
DE retinal degenerative diseases; mesenchymal stem cells; stem cell
   therapy; experimental models; clinical trials
ID MARROW STROMAL CELLS; BONE-MARROW; SODIUM IODATE; ANIMAL-MODELS;
   GROWTH-FACTOR; T-CELL; LYMPHOCYTE-PROLIFERATION; INTERFERON-GAMMA;
   ADIPOSE-TISSUE; IN-VITRO
AB Retinal degenerative diseases, such as age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy or glaucoma, represent the main causes of a decreased quality of vision or even blindness worldwide. However, despite considerable efforts, the treatment possibilities for these disorders remain very limited. A perspective is offered by cell therapy using mesenchymal stem cells (MSCs). These cells can be obtained from the bone marrow or adipose tissue of a particular patient, expanded in vitro and used as the autologous cells. MSCs possess potent immunoregulatory properties and can inhibit a harmful inflammatory reaction in the diseased retina. By the production of numerous growth and neurotrophic factors, they support the survival and growth of retinal cells. In addition, MSCs can protect retinal cells by antiapoptotic properties and could contribute to the regeneration of the diseased retina by their ability to differentiate into various cell types, including the cells of the retina. All of these properties indicate the potential of MSCs for the therapy of diseased retinas. This view is supported by the recent results of numerous experimental studies in different preclinical models. Here we provide an overview of the therapeutic properties of MSCs, and their use in experimental models of retinal diseases and in clinical trials.
C1 [Holan, Vladimir; Palacka, Katerina; Hermankova, Barbora] Czech Acad Sci, Inst Expt Med, Dept Nanotoxicol & Mol Epidemiol, Prague 14220, Czech Republic.
   [Holan, Vladimir; Palacka, Katerina] Charles Univ Prague, Fac Sci, Dept Cell Biol, Prague 12843, Czech Republic.
C3 Czech Academy of Sciences; Charles University Prague
RP Holan, V (通讯作者)，Czech Acad Sci, Inst Expt Med, Dept Nanotoxicol & Mol Epidemiol, Prague 14220, Czech Republic.; Holan, V (通讯作者)，Charles Univ Prague, Fac Sci, Dept Cell Biol, Prague 12843, Czech Republic.
EM vladimir.holan@iem.cas.cz; katerina.palacka@iem.cas.cz;
   barbora.hermankova@iem.cas.cz
FU Grant Agency of the Czech Republic [19-02290S]; Charles University [SVV
   260435, 20604315 PROGRES Q43]
FX This work was supported the grant No. 19-02290S from the Grant Agency of
   the Czech Republic and by the Charles University programs SVV 260435 and
   20604315 PROGRES Q43.
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NR 177
TC 16
Z9 16
U1 4
U2 14
PU MDPI
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
EI 2073-4409
J9 CELLS-BASEL
JI Cells
PD MAR
PY 2021
VL 10
IS 3
AR 588
DI 10.3390/cells10030588
PG 21
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA RD4VX
UT WOS:000633478800001
PM 33799995
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Li, QQ
   Weng, JW
   Wong, SN
   Lee, WYT
   Chow, SF
AF Li, Qingqing
   Weng, Jingwen
   Wong, Si Nga
   Lee, Wai Yip Thomas
   Chow, Shing Fung
TI Nanoparticulate Drug Delivery to the Retina
SO MOLECULAR PHARMACEUTICS
LA English
DT Review
DE nanoparticle; retinal diseases; ocular delivery; ocular barriers;
   delivery efficiency
ID PEG-PCL MICELLES; POSTERIOR SEGMENT; GENE DELIVERY; LONG-TERM; IN-VITRO;
   PROLIFERATIVE VITREORETINOPATHY; DENDRIMER NANOPARTICLES; INTRAVITREAL
   INJECTION; GOLD NANOPARTICLES; PIGMENT EPITHELIUM
AB Retinal diseases, such as age-related macular degeneration and diabetic retinopathy, are the leading causes of blindness worldwide. The mainstay of treatment for these blinding diseases remains to be surgery, and the available pharmaceutical therapies on the market are limited, partially owing to various biological barriers in hindering the delivery of therapeutics to the retina. The nanoparticulate drug delivery system confers the capability for delivering therapeutics to the specific ocular targets and, hence, potentially revolutionizes the current treatment landscape of retinal diseases. While the research to date indicates the enormous therapeutics potentials of the nanoparticulate delivery systems, the successful translation of these systems from the bench to bedside is challenging and requires a combined understanding of retinal pathology, physiology of the eye, and particle and formulation designs of nanoparticles. To this end, the review begins with an overview of the most prevalent retinal diseases and related pharmacotherapy. Highlights of the current challenges encountered in ocular drug delivery for each administration route are provided, followed by critical appraisal of various nanoparticulate drug delivery systems for the retinal diseases, including their formulation designs, therapeutic merits, limitations, and future direction. It is believed that a greater understanding of the nano-biointeraction in eyes will lead to the development of more sophisticated drug delivery systems for retinal diseases.
C1 [Li, Qingqing] Xi An Jiao Tong Univ, Fac Pharm, Hlth Sci Ctr, Xian 710049, Peoples R China.
   [Weng, Jingwen; Wong, Si Nga; Chow, Shing Fung] Univ Hong Kong, Li Ka Shing Fac Med, Dept Pharmacol & Pharm, Pok Fu Lam, Hong Kong, Peoples R China.
   [Lee, Wai Yip Thomas] Aptorum Grp Ltd, Shatin New Town, Hong Kong, Peoples R China.
C3 Xi'an Jiaotong University; University of Hong Kong
RP Chow, SF (通讯作者)，Univ Hong Kong, Li Ka Shing Fac Med, Dept Pharmacol & Pharm, Pok Fu Lam, Hong Kong, Peoples R China.; Lee, WYT (通讯作者)，Aptorum Grp Ltd, Shatin New Town, Hong Kong, Peoples R China.
EM thomas.lee@aptorumgroup.com; asfchow@hku.hk
OI Chow, Shing Fung/0000-0002-4588-5346; Lee, Thomas/0000-0001-8217-7392;
   Weng, Jingwen/0000-0002-2673-9132
FU Basic research program of the Natural Science Foundation of Shaanxi
   province [2020JQ-093]; University of Hong Kong [202007002]
FX We gratefully acknowledge financial supports from the Basic research
   program of the Natural Science Foundation of Shaanxi province
   (2020JQ-093) and the University of Hong Kong (202007002).
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NR 155
TC 13
Z9 14
U1 7
U2 48
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1543-8384
EI 1543-8392
J9 MOL PHARMACEUT
JI Mol. Pharm.
PD FEB 1
PY 2021
VL 18
IS 2
BP 506
EP 521
DI 10.1021/acs.molpharmaceut.0c00224
PG 16
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA RP8FB
UT WOS:000641957900005
PM 32501716
DA 2022-11-30
ER

PT J
AU Keeling, E
   Chatelet, DS
   Tan, NYT
   Khan, F
   Richards, R
   Thisainathan, T
   Goggin, P
   Page, A
   Tumbarello, DA
   Lotery, AJ
   Ratnayaka, JA
AF Keeling, Eloise
   Chatelet, David S.
   Tan, Nicole Y. T.
   Khan, Farihah
   Richards, Rhys
   Thisainathan, Thibana
   Goggin, Patricia
   Page, Anton
   Tumbarello, David A.
   Lotery, Andrew J.
   Ratnayaka, J. Arjuna
TI 3D-Reconstructed Retinal Pigment Epithelial Cells Provide Insights into
   the Anatomy of the Outer Retina
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE retinal pigment epithelium (RPE); 3D reconstruction; retina; mouse;
   SBF-SEM; photoreceptors; imaging; age-related macular degeneration (AMD)
ID MOUSE MODEL; HUMAN RPE; AGE; DEGENERATION; TOPOGRAPHY; PATHOLOGY;
   MEMBRANE; DEFECTS; DENSITY; DRUSEN
AB The retinal pigment epithelium (RPE) is located between the neuroretina and the choroid, and plays a critical role in vision. RPE cells internalise outer segments (OS) from overlying photoreceptors in the daily photoreceptor renewal. Changes to RPE structure are linked with age and retinopathy, which has been described in the past by conventional 2D electron microscopy. We used serial block face scanning electron microscopy (SBF-SEM) to reconstruct RPE cells from the central mouse retina. Three-dimensional-reconstructed OS revealed the RPE to support large numbers of photoreceptors (90-216 per RPE cell). Larger bi-nucleate RPE maintained more photoreceptors, although their cytoplasmic volume was comparable to smaller mono-nucleate RPE supporting fewer photoreceptors. Scrutiny of RPE microvilli and interdigitating OS revealed the angle and surface area of contact between RPE and photoreceptors. Bi-nucleate RPE contained more mitochondria compared to mono-nucleate RPE. Furthermore, bi-nucleate cells contained larger sub-RPE spaces, supporting a likely association with disease. Use of perfusion-fixed tissues ensured the highest possible standard of preservation, providing novel insights into the 3D RPE architecture and changes linked with retinopathy. This study serves as a benchmark for comparing retinal tissues from donor eyes with age-related macular degeneration (AMD) and other retinopathies.
C1 [Keeling, Eloise; Tan, Nicole Y. T.; Khan, Farihah; Richards, Rhys; Thisainathan, Thibana; Lotery, Andrew J.; Ratnayaka, J. Arjuna] Univ Southampton, Fac Med, Clin & Expt Sci, MP806,Tremona Rd, Southampton SO16 6YD, Hants, England.
   [Chatelet, David S.; Goggin, Patricia; Page, Anton] Univ Southampton, Biomed Imaging Unit, MP12,Tremona Rd, Southampton SO16 6YD, Hants, England.
   [Tumbarello, David A.] Univ Southampton, Fac Environm & Life Sci, Biol Sci, Life Sci Bldg 85,Highfield Campus, Southampton SO17 1BJ, Hants, England.
   [Lotery, Andrew J.] Univ Hosp Southampton NHS Fdn Trust, Eye Unit, Southampton SO16 6YD, Hants, England.
C3 University of Southampton; University of Southampton; University of
   Southampton; University of Southampton; University Hospital Southampton
   NHS Foundation Trust
RP Ratnayaka, JA (通讯作者)，Univ Southampton, Fac Med, Clin & Expt Sci, MP806,Tremona Rd, Southampton SO16 6YD, Hants, England.
EM E.E.Keeling@soton.ac.uk; D.S.Chatelet@soton.ac.uk; nytt1e13@soton.ac.uk;
   fk3g15@soton.ac.uk; rr5g15@soton.ac.uk; tt1e16@soton.ac.uk;
   P.Goggin@soton.ac.uk; A.Page@soton.ac.uk; D.A.Tumbarello@soton.ac.uk;
   A.J.Lotery@soton.ac.uk; J.Ratnayaka@soton.ac.uk
OI Keeling, Eloise/0000-0003-0399-359X; Tumbarello,
   David/0000-0002-5169-0561; Ratnayaka, J. Arjuna/0000-0002-1027-6938;
   Lotery, Andrew/0000-0001-5541-4305; Goggin, Patricia/0000-0003-4730-0206
FU UK Macular Society; Gift of Sight Appeal
FX This research was funded by awards to J.A.R. from the UK Macular Society
   and the Gift of Sight Appeal.
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NR 53
TC 9
Z9 9
U1 0
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 NOV
PY 2020
VL 21
IS 21
AR 8408
DI 10.3390/ijms21218408
PG 16
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Chemistry
GA OQ7WO
UT WOS:000588988800001
PM 33182490
OA gold, Green Published
DA 2022-11-30
ER

PT J
AU Olson, JL
   Velez-Montoya, R
   Mackin, A
   Manoharan, N
   Mueller, N
   Erlanger, M
AF Olson, Jeffrey L.
   Velez-Montoya, Raul
   Mackin, Anna
   Manoharan, Niranjan
   Mueller, Niklaus
   Erlanger, Michael
TI Vitreous protein binding with nanopore dialysis membrane device
SO BIOMEDICAL MICRODEVICES
LA English
DT Article
DE Retina; Macular degeneration; Complement factors; Intravitreal drugs
ID MACULAR DEGENERATION; CURRENT KNOWLEDGE; GENETICS; TRENDS
AB Age-related macular degeneration (AMD) is one of the leading causes of blindness in the industrialized world, affecting over 8 million patients in the United State alone. While the wet (exudative) form of the disease is treated with intraocular injections, there are currently no approved therapies available for the dry (non-exudative) form of the disease which often affects both eyes in patients with AMD. Current research has focused on developing drugs that can be injected into the eye, but the treatment burden associated with monthly injections limits the effectiveness of this approach. Hence, there is a pressing need for a long-term therapeutic solution for patients suffering from this blinding disease. We detail a novel implantable intraocular device, which adsorbs and traps complement factors associated with AMD. In this study, we tested a novel approach by dialyzing proteins from the vitreous using biocompatible implants composed of a nanopore polyacrylonitrile polymer membrane. Preliminaryin vitroandin vivostudies demonstrate a high affinity and capacity for complement protein absorption. After a three-month implantation in New Zealand White Cross rabbits, the implant demonstrated good biocompatibility with no inflammation and normal retinal physiology and histology. These studies demonstrate that prolonged CF suppression intraocularly may be accomplished with a nanopore polymer membrane.
C1 [Olson, Jeffrey L.; Velez-Montoya, Raul; Mackin, Anna; Manoharan, Niranjan; Mueller, Niklaus; Erlanger, Michael] Univ Colorado, Sue Anschutz Rodgers Eye Ctr, Dept Ophthalmol, Sch Med, 1675 Aurora Court,Mailstop F731, Aurora, CO 80045 USA.
C3 University of Colorado System; University of Colorado Anschutz Medical
   Campus
RP Olson, JL (通讯作者)，Univ Colorado, Sue Anschutz Rodgers Eye Ctr, Dept Ophthalmol, Sch Med, 1675 Aurora Court,Mailstop F731, Aurora, CO 80045 USA.
EM Jeffrey.Olson@cuanschutz.edu
FU Colorado Bioscience Discovery Evaluation Grant Program; Gates Center for
   Regenerative Medicine
FX This project was supported in part by funding from the Colorado
   Bioscience Discovery Evaluation Grant Program and the Gates Center for
   Regenerative Medicine.
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NR 17
TC 0
Z9 0
U1 0
U2 2
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 JUL 4
PY 2020
VL 22
IS 3
AR 46
DI 10.1007/s10544-020-00500-9
PG 6
WC Engineering, Biomedical; Nanoscience & Nanotechnology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Engineering; Science & Technology - Other Topics
GA MF2XG
UT WOS:000545209800001
PM 32623529
DA 2022-11-30
ER

PT J
AU Sudharsan, R
   Beiting, DP
   Aguirre, GD
   Beltran, WA
AF Sudharsan, Raghavi
   Beiting, Daniel P.
   Aguirre, Gustavo D.
   Beltran, William A.
TI Involvement of Innate Immune System in Late Stages of Inherited
   Photoreceptor Degeneration
SO SCIENTIFIC REPORTS
LA English
DT Article
ID NLRP3 INFLAMMASOME ACTIVATION; TOLL-LIKE RECEPTORS; CELL-DEATH; MACULAR
   DEGENERATION; COMPLEMENT-SYSTEM; RETINAL DEGENERATION; CUTTING EDGE;
   BETA-SUBUNIT; MUTATION; GENE
AB Retinitis pigmentosa (RP) is a group of inherited retinal degenerations that lead to progressive vision loss. Over 200 mutations in 60 different genes have been shown to cause RP. Given the diversity of genes and mutations that cause RP, corrective gene therapy approaches currently in development may prove both time-consuming and cost-prohibitive for treatment of all forms of RP. An alternative approach is to find common biological pathways that cause retinal degeneration in various forms of RP, and identify new molecular targets. With this goal, we analyzed the retinal transcriptome of two nonallelic forms of RP in dogs, rcd1 and xlpra2, at clinically relevant advanced stages of the two diseases. Both diseases showed very similar trends in changes in gene expression compared to control normal dogs. Pathway analysis revealed upregulation of various components of the innate immune system in both diseases, including inflammasome and complement pathways. Our results show that the retinal transcriptome at advanced stages of RP is very similar to that of other retinal degenerative diseases such as age-related macular degeneration and diabetic retinopathy. Thus, drugs and therapeutics already in development for targeting these retinopathies may also prove useful for the treatment of many forms of RP.
C1 [Sudharsan, Raghavi; Aguirre, Gustavo D.; Beltran, William A.] Univ Penn, Sch Vet Med, Dept Clin Sci & Adv Med, Div Expt Retinal Therapies, Philadelphia, PA 19104 USA.
   [Beiting, Daniel P.] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; University of Pennsylvania
RP Beltran, WA (通讯作者)，Univ Penn, Sch Vet Med, Dept Clin Sci & Adv Med, Div Expt Retinal Therapies, Philadelphia, PA 19104 USA.
EM wbeltran@vet.upenn.edu
RI Beiting, Daniel/AAG-6275-2019
OI Aguirre, Gustavo/0000-0002-5228-256X
FU NIH [R24EY022012, RO1EY06855, RO1EY17549]; Foundation Fighting
   Blindness; Van Sloun Fund for Canine Genetic Research, Hope for Vision;
   NATIONAL EYE INSTITUTE [R01EY017549, R24EY022012, R01EY006855] Funding
   Source: NIH RePORTER
FX We thank Lydia Melnyk for research coordination and RDSF staff for
   animal husbandry. This work was supported by grants from NIH
   (R24EY022012, RO1EY06855, RO1EY17549), the Foundation Fighting
   Blindness, the Van Sloun Fund for Canine Genetic Research, Hope for
   Vision.
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NR 84
TC 22
Z9 22
U1 0
U2 3
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD DEC 20
PY 2017
VL 7
AR 17897
DI 10.1038/s41598-017-18236-7
PG 12
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA FQ5HE
UT WOS:000418388700017
PM 29263354
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Suda, K
   Murakami, T
   Gotoh, N
   Fukuda, R
   Hashida, Y
   Hashida, M
   Tsujikawa, A
   Yoshimura, N
AF Suda, Kenji
   Murakami, Tatsuya
   Gotoh, Norimoto
   Fukuda, Ryosuke
   Hashida, Yasuhiko
   Hashida, Mitsuru
   Tsujikawa, Akitaka
   Yoshimura, Nagahisa
TI High-density lipoprotein mutant eye drops for the treatment of posterior
   eye diseases
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article
DE Ocular drug delivery; Age-related macular degeneration; Serum protein;
   Phospholipid, cell-penetrating peptide; Anti-angiogenesis drug
ID APOLIPOPROTEIN-A-I; MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION;
   DRUG-DELIVERY; HEART-DISEASE; NANOPARTICLES; RANIBIZUMAB; CHOLESTEROL;
   PAZOPANIB; THERAPY
AB Age-related macular degeneration (AMD), in which choroidal neovascularization (CNV) affects the center of the retina (macula), leads to the irreversible visual loss. The intravitreal injection of anti-angiogenesis antibodies improved the prognosis of AMD, but relatively less invasive therapies should be explored. In the present study, we show that a high-density lipoprotein (HDL) mutant is a therapeutically active drug carrier capable of treating a posterior eye disease in mice via instillation. Various HDL mutants were prepared with apoA-I proteins fused with different cell-penetrating peptides (CPPs) and phospholipids with different alkyl chain lengths; their sizes were further controlled in the range of 10-25 nm. They were screened based on the efficiency of fluorescent dye delivery to the inner retinal layer in mice. The best mutant was found to have penetratin (PEN) as a CPP, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), and a size of 15 nm. In preclinical studies on a laser-induced CNV murine model, 1 week of instillation of the best mutant carrying the anti-angiogenesis drug pazopanib had dramatic therapeutic effects in reducing the CNV size. Importantly, the HDL mutant by itself contributed to the therapeutic effects. Future clinical trials for treating AMD with instillation of the HDL mutant are expected.
C1 [Suda, Kenji; Gotoh, Norimoto; Tsujikawa, Akitaka; Yoshimura, Nagahisa] Kyoto Univ, Dept Ophthalmol & Visual Sci, Grad Sch Med, Kyoto, Japan.
   [Murakami, Tatsuya; Fukuda, Ryosuke] Toyama Prefectural Univ, Grad Sch Engn, Dept Biotechnol, Toyama, Japan.
   [Murakami, Tatsuya; Hashida, Yasuhiko; Hashida, Mitsuru] Kyoto Univ, Inst Integrated Cell Mat Sci, Kyoto, Japan.
   [Hashida, Mitsuru] Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Drug Delivery Res, Kyoto, Japan.
C3 Kyoto University; Toyama Prefectural University; Kyoto University; Kyoto
   University
RP Murakami, T (通讯作者)，Toyama Prefectural Univ, Grad Sch Engn, Dept Biotechnol, Toyama, Japan.
EM murakami@pu-toyama.ac.jp
RI Song, Eun Joo/Z-5130-2019; SUDA, Kenji/W-1979-2019
OI SUDA, Kenji/0000-0003-1636-0898; Fukuda, Ryosuke/0000-0003-2509-3314;
   Tsujikawa, Akitaka/0000-0003-0779-7799; Murakami,
   Tatsuya/0000-0001-5199-500X; hashida, mitsuru/0000-0001-7383-8080
FU World Premier International Research Center Initiative (WPI); Ministry
   of Education, Culture, Sports, Science, amp;amp;amp; Technology (MEXT),
   Japan; Japan Society for the Promotion of Science (JSPS), Japan, Kyoto
   City; Suzuken Memorial Foundation; CASIO Science Promotion Foundation; 
   [26670754];  [16H06909]
FX This study was supported in part by the World Premier International
   Research Center Initiative (WPI), the Ministry of Education, Culture,
   Sports, Science, & Technology (MEXT), Japan, and Grant-in-Aids for
   Scientific Research (no. 26670754 [N.G.] and no. 16H06909 [K.S.]), the
   Japan Society for the Promotion of Science (JSPS), Japan, Kyoto City
   (K.S., T.M.), Suzuken Memorial Foundation (T.M.), and CASIO Science
   Promotion Foundation (T.M.).
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NR 45
TC 20
Z9 21
U1 1
U2 21
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-3659
EI 1873-4995
J9 J CONTROL RELEASE
JI J. Control. Release
PD NOV 28
PY 2017
VL 266
BP 301
EP 309
DI 10.1016/j.jconrel.2017.09.036
PG 9
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Chemistry; Pharmacology & Pharmacy
GA FP0VJ
UT WOS:000417325400027
PM 28987881
OA Green Submitted
DA 2022-11-30
ER

PT J
AU Riddell, N
   Crewther, SG
AF Riddell, Nina
   Crewther, Sheila G.
TI Novel evidence for complement system activation in chick myopia and
   hyperopia models: a meta-analysis of transcriptome datasets
SO SCIENTIFIC REPORTS
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; DIFFERENTIALLY EXPRESSED GENES;
   FORM-DEPRIVATION MYOPIA; EYE GROWTH-REGULATION; CHOROIDAL
   NEOVASCULARIZATION; MACULAR DEGENERATION; OXIDATIVE STRESS; MICROARRAY
   ANALYSIS; REFRACTIVE ERROR; OCULAR GROWTH
AB Myopia (short-sightedness) and hyperopia (long-sightedness) occur when the eye grows too long or short, respectively, for its refractive power. There are currently approximately 1.45 billion myopes worldwide and prevalence is rising dramatically. Although high myopia significantly increases the risk of developing a range of sight-threatening disorders, the molecular mechanisms underlying ocular growth regulation and its relationship to these secondary complications remain poorly understood. Thus, this study meta-analyzed transcriptome datasets collected in the commonly used chick model of optically-induced refractive error. Fifteen datasets (collected across five previous studies) were obtained from GEO, preprocessed in Bioconductor, and divided into 4 conditions representing early (<= 1 day) and late (>1 day) myopia and hyperopia induction. Differentially expressed genes in each condition were then identified using Rank Product meta-analysis. The results provide novel evidence for transcriptional activation of the complement system during both myopia and hyperopia induction, and confirm existing literature implicating cell signaling, mitochondrial, and structural processes in refractive error. Further comparisons demonstrated that the meta-analysis results also significantly improve concordance with broader omics data types (i.e., human genetic association and animal proteomics studies) relative to previous transcriptome studies, and show extensive similarities with the genes linked to age-related macular degeneration, choroidal neovascularization, and cataract.
C1 [Riddell, Nina; Crewther, Sheila G.] La Trobe Univ, Sch Psychol & Publ Hlth, Dept Psychol & Counselling, Melbourne, Vic 3086, Australia.
C3 La Trobe University
RP Crewther, SG (通讯作者)，La Trobe Univ, Sch Psychol & Publ Hlth, Dept Psychol & Counselling, Melbourne, Vic 3086, Australia.
EM S.Crewther@latrobe.edu.au
RI Crewther, Sheila G/A-2165-2008
OI Riddell, Nina/0000-0003-3341-5862
FU Australia Research Council [DP110103784]; Australian Government
FX Supported by Australia Research Council Grant DP110103784 to DPC and
   SGC, and by Australian Government Research Training Program Scholarship
   to N.R.
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NR 108
TC 25
Z9 25
U1 0
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD AUG 29
PY 2017
VL 7
AR 9719
DI 10.1038/s41598-017-10277-2
PG 14
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA FE9QJ
UT WOS:000408537900001
PM 28852117
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Takei, A
   Ekstrom, M
   Mammadzada, P
   Aronsson, M
   Yu, M
   Kvanta, A
   Andre, H
AF Takei, Anna
   Ekstrom, Malena
   Mammadzada, Parviz
   Aronsson, Monica
   Yu, Ma
   Kvanta, Anders
   Andre, Helder
TI Gene Transfer of Prolyl Hydroxylase Domain 2 Inhibits Hypoxia-inducible
   Angiogenesis in a Model of Choroidal Neovascularization
SO SCIENTIFIC REPORTS
LA English
DT Article
ID UBIQUITIN-PROTEASOME PATHWAY; ENDOTHELIAL GROWTH-FACTOR;
   TUMOR-SUPPRESSOR PROTEIN; MACULAR DEGENERATION; FACTOR-I; OCULAR
   ANGIOGENESIS; FACTOR 1-ALPHA; HIF-ALPHA; CELLS; FACTOR-1-ALPHA
AB Cellular responses to hypoxia are mediated by the hypoxia-inducible factors (HIF). In normoxia, HIF-alpha proteins are regulated by a family of dioxygenases, through prolyl and asparagyl hydroxylation, culminating in proteasomal degradation and transcriptional inactivation. In hypoxia, the dioxygenases become inactive and allow formation of HIF transcription factor, responsible for upregulation of hypoxia genes. In ocular neoangiogenic diseases, such as neovascular age-related macular degeneration (nAMD), hypoxia seems pivotal. Here, we investigate the effects of HIF regulatory proteins on the hypoxia pathway in retinal pigment epithelium (RPE) cells, critically involved in nAMD pathogenesis. Our data indicates that, in ARPE-19 cells, prolyl hydroxylase domain (PHD)2 is the most potent negative-regulator of the HIF pathway. The negative effects of PHD2 on the hypoxia pathway were associated with decreased HIF-1 alpha protein levels, and concomitant decrease in angiogenic factors. ARPE-19 cells stably expressing PHD2 impaired angiogenesis in vitro by wound healing, tubulogenesis, and sprouting assays, as well as in vivo by iris-induced angiogenesis. Gene transfer of PHD2 in vivo resulted in mitigation of HIF-mediated angiogenesis in a mouse model of nAMD. These results may have implications for the clinical treatment of nAMD patients, particularly regarding the use of gene therapy to negatively regulate neoangiogenesis.
C1 [Takei, Anna; Ekstrom, Malena; Mammadzada, Parviz; Aronsson, Monica; Yu, Ma; Kvanta, Anders; Andre, Helder] St Erik Eye Hosp, Karolinska Inst, Dept Clin Neurosci, Sect Ophthalmol & Vis, Stockholm, Sweden.
C3 Karolinska Institutet
RP Andre, H (通讯作者)，St Erik Eye Hosp, Karolinska Inst, Dept Clin Neurosci, Sect Ophthalmol & Vis, Stockholm, Sweden.
EM helder.andre@ki.se
RI Andre, Helder/AAC-5220-2019
OI Andre, Helder/0000-0002-2926-2376; Mammadzada,
   Parviz/0000-0003-4171-5291
FU Crown Princess Margareta Association for the Visually Impaired;
   Cronqvist Foundation; Edwin Jordan Foundation; Tore Nilsson Foundation;
   Swedish Eye Foundation; Karolinska Institutet; Swedish Research Council;
   Genentech Age-related Macular Degeneration Fellowships; Swedish
   Institute
FX We thank Selcuk Tunik and Husai Afzali for technical assistance, Malin
   Langhals for critical review of the manuscript, and Linnea Tankred for
   animal husbandry. This study was supported by the Crown Princess
   Margareta Association for the Visually Impaired, the Cronqvist
   Foundation, the Edwin Jordan Foundation, the Tore Nilsson Foundation,
   the Swedish Eye Foundation, the Karolinska Institutet, the Swedish
   Research Council, and the Genentech Age-related Macular Degeneration
   Fellowships. Ma Yu was partly supported by a scholarship from the
   Swedish Institute.
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NR 49
TC 12
Z9 13
U1 0
U2 15
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 FEB 10
PY 2017
VL 7
AR 42546
DI 10.1038/srep42546
PG 14
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA EK8VR
UT WOS:000394203200001
PM 28186209
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Thomas, SE
   Harrison, EH
AF Thomas, Sara E.
   Harrison, Earl H.
TI Mechanisms of selective delivery of xanthophylls to retinal pigment
   epithelial cells by human lipoproteins
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE dietary lipids; scavenger receptors; low density lipoprotein; high
   density lipoprotein; transport; carotenoids; eye; retina; lutein;
   zeaxanthin
ID RECEPTOR CLASS-B; HIGH-DENSITY-LIPOPROTEIN; FAT-SOLUBLE VITAMINS; I
   SR-BI; MESO-ZEAXANTHIN; BETA-CAROTENE; MACULAR DEGENERATION; BASOLATERAL
   SECRETION; ALPHA-TOCOPHEROL; LIPID TRANSPORT
AB The xanthophylls, lutein and zeaxanthin, are dietary carotenoids that selectively accumulate in the macula of the eye providing protection against age-related macular degeneration. To reach the macula, carotenoids cross the retinal pigment epithelium (RPE). Xanthophylls and beta-carotene mostly associate with HDL and LDL, respectively. HDL binds to cells via a scavenger receptor class B1 (SR-B1)-dependent mechanism, while LDL binds via the LDL receptor. Using an in-vitro, human RPE cell model (ARPE-19), we studied the mechanisms of carotenoid uptake into the RPE by evaluating kinetics of cell uptake when delivered in serum or isolated LDL or HDL. For lutein and beta-carotene, LDL delivery resulted in the highest rates and extents of uptake. In contrast, HDL was more effective in delivering zeaxanthin and meso-zeaxanthin leading to the highest rates and extents of uptake of all four carotenoids. Inhibitors of SR-B1 suppressed zeaxanthin delivery via HDL. Results show a selective HDL-mediated uptake of zeaxanthin and meso-zeaxanthin via SR-B1 and a LDL-mediated uptake of lutein. This demonstrates a plausible mechanism for the selective accumulation of zeaxanthin greater than lutein and xanthophylls over beta-carotene in the retina. We found no evidence of xanthophyll metabolism to apocarotenoids or lutein conversion to meso-zeaxanthin.
C1 [Thomas, Sara E.; Harrison, Earl H.] Ohio State Univ, Dept Human Sci, Columbus, OH 43210 USA.
C3 University System of Ohio; Ohio State University
RP Harrison, EH (通讯作者)，Ohio State Univ, Dept Human Sci, Columbus, OH 43210 USA.
EM Harrison.304@osu.edu
RI Harrison, Earl H/AAN-5378-2021
OI Thomas, Sara/0000-0003-0686-9500
FU National Heart, Lung, and Blood Institute [RO1-HL049879]; NATIONAL
   HEART, LUNG, AND BLOOD INSTITUTE [R01HL049879] Funding Source: NIH
   RePORTER; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY
   DISEASES [R01DK101251] Funding Source: NIH RePORTER
FX This work was supported by National Heart, Lung, and Blood Institute
   Grant RO1-HL049879. The content is solely the responsibility of the
   authors and does not necessarily represent the official views of the
   National Institutes of Health. The authors declare that they have no
   conflicts of interest.
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NR 65
TC 42
Z9 42
U1 1
U2 20
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0022-2275
EI 1539-7262
J9 J LIPID RES
JI J. Lipid Res.
PD OCT
PY 2016
VL 57
IS 10
BP 1865
EP 1878
DI 10.1194/jlr.M070193
PG 14
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA EB2ZR
UT WOS:000387231600012
PM 27538825
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Zernii, EY
   Baksheeva, VE
   Iomdina, EN
   Averina, OA
   Permyakov, SE
   Philippov, PP
   Zamyatnin, AA
   Senin, II
AF Zernii, Evgeni Y.
   Baksheeva, Viktoriia E.
   Iomdina, Elena N.
   Averina, Olga A.
   Permyakov, Sergei E.
   Philippov, Pavel P.
   Zamyatnin, Andrey A., Jr.
   Senin, Ivan I.
TI Rabbit Models of Ocular Diseases: New Relevance for Classical Approaches
SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
LA English
DT Article
DE Ocular diseases; experimental animal models; rabbit; ocular
   pharmacology; dry eye syndrome; glaucoma; age-related macular
   degeneration; cataract; uveitis
ID ENDOTOXIN-INDUCED UVEITIS; DRY EYE DISEASE; RETINAL-PIGMENT EPITHELIUM;
   GANGLION-CELL DEATH; INDUCED PHOTORECEPTOR APOPTOSIS; LASER-INDUCED
   GLAUCOMA; OPTIC-NERVE HEAD; MACULAR DEGENERATION; INTRAOCULAR-PRESSURE;
   DRUG-DELIVERY
AB Over 100 million individuals are affected by irreversible visual impairments and blindness worldwide, while ocular diseases remain a challenging problem despite significant advances in modern ophthalmology. Development of novel drugs and drug delivery mechanisms, as well as advanced ophthalmological techniques requires experimental models including animals, capable of developing ocular diseases with similar etiology and pathology, suitable for future trials of new therapeutic approaches. Although experimental ophthalmology and visual research are traditionally performed on rodent models, these animals are often unsuitable for pre-clinical drug efficacy and safety studies, as well as for testing novel drug delivery approaches, e.g. controlled release of pharmaceuticals using intra-ocular implants. Therefore, rabbit models of ocular diseases are particularly useful in this context, since rabbits can be easily handled, while sharing more common anatomical and biochemical features with humans compared to rodents, including longer life span and larger eye size. This review provides a brief description of clinical, morphological and mechanistic aspects of the most common ocular diseases (dry eye syndrome, glaucoma, age-related macular degeneration, light-induced retinopathies, cataract and uveitis) and summarizes the diversity of current strategies for their experimental modeling in rabbits. Several applications of some of these models in ocular pharmacology and eye care strategies are also discussed.
C1 [Zernii, Evgeni Y.; Baksheeva, Viktoriia E.; Averina, Olga A.; Philippov, Pavel P.; Zamyatnin, Andrey A., Jr.; Senin, Ivan I.] Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, 1-40 Leninskye Gory, Moscow 119992, Russia.
   [Iomdina, Elena N.] Moscow Helmholtz Res Inst Eye Dis, Moscow 105062, Russia.
   [Permyakov, Sergei E.] Russian Acad Sci, Inst Biol Instrumentat, Pushchino 142290, Moscow Region, Russia.
   [Zamyatnin, Andrey A., Jr.] Sechenov First Moscow State Med Univ, Inst Mol Med, Moscow 119991, Russia.
C3 Lomonosov Moscow State University; Helmholtz National Medical Research
   Center of Eye Diseases; Russian Academy of Sciences; Sechenov First
   Moscow State Medical University
RP Senin, II (通讯作者)，Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, 1-40 Leninskye Gory, Moscow 119992, Russia.
EM senin@belozersky.msu.ru
RI Zamyatnin, Andrey A./D-6443-2012; Averina, Olga/AAD-2955-2019; Iomdina,
   Elena/AAB-3289-2020; Permyakov, Sergei/O-1386-2019; Viktoriia, Baksheeva
   E/Q-8035-2018; Zernii, Evgeni Yu./D-9446-2012; Baksheeva,
   Viktoriia/AAO-3153-2020; Permyakov, Sergei E./B-8156-2011
OI Zamyatnin, Andrey A./0000-0002-3046-4565; Permyakov,
   Sergei/0000-0003-4086-3137; Zernii, Evgeni Yu./0000-0002-3013-7863;
   Baksheeva, Viktoriia/0000-0002-0445-2667; Permyakov, Sergei
   E./0000-0003-4086-3137; Averina, Olga/0000-0002-8244-526X
FU Russian Foundation for Basic Research [15-04-07963-a, 15-04-05171,
   15-04-99543]; Program of Russian Academy of Sciences "Molecular and
   Cellular Biology"
FX This work was supported by grants from the Russian Foundation for Basic
   Research (E.Yu.Z., No15-04-07963-a; P.P.Ph. No15-04-05171; A.A.Z.
   No15-04-99543) and by a grant from the Program of the Russian Academy of
   Sciences "Molecular and Cellular Biology" (S.E.P.). We are indebted to
   Dr. Alexander Borodavka (University of Leeds, Leeds, United Kingdom) and
   Prof. Eugene A. Permyakov (IBI RAS, Pushchino, Russia) for careful
   reading and correction of the manuscript.
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NR 264
TC 46
Z9 53
U1 0
U2 30
PU BENTHAM SCIENCE PUBL
PI BUSUM
PA PO BOX 294, BUSUM, 1400 AG, NETHERLANDS
SN 1871-5273
EI 1996-3181
J9 CNS NEUROL DISORD-DR
JI CNS Neurol. Disord.-Drug Targets
PY 2016
VL 15
IS 3
BP 267
EP 291
DI 10.2174/1871527315666151110124957
PG 25
WC Neurosciences; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA DI9DH
UT WOS:000373801100003
PM 26553163
DA 2022-11-30
ER

PT J
AU Semeraro, F
   Russo, A
   Gambicorti, E
   Duse, S
   Morescalchi, F
   Vezzoli, S
   Costagliola, C
AF Semeraro, Francesco
   Russo, Andrea
   Gambicorti, Elena
   Duse, Sarah
   Morescalchi, Francesco
   Vezzoli, Sara
   Costagliola, Ciro
TI Efficacy and vitreous levels of topical NSAIDs
SO EXPERT OPINION ON DRUG DELIVERY
LA English
DT Review
DE inflammation; NSAIDs; retinal disease; vitreous penetration
ID DIABETIC MACULAR EDEMA; NONSTEROIDAL ANTIINFLAMMATORY DRUGS;
   THROMBOEMBOLIC ADVERSE EVENTS; INDUCED OCULAR INFLAMMATION; RANDOMIZED
   CONTROLLED-TRIAL; ENDOTHELIAL GROWTH-FACTOR; PROSTAGLANDIN E-2 LEVELS;
   ANTI-VEGF DRUGS; INTRAVITREAL INJECTION; KETOROLAC TROMETHAMINE
AB Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed medications and are routinely used for their analgesic, antipyretic, and anti-inflammatory properties. Because of their potent cyclooxygenase-inhibitory activity, they can inhibit pro-inflammatory prostaglandin synthesis, leading to complex inflammatory cascades. NSAIDs have been broadly used systemically for many decades and have recently become commercially available in the form of topical ophthalmic formulations. NSAIDs are weak acids with pK(a) values mostly between 3.5 and 4.5 and are poorly water-soluble. New, aqueous ophthalmic solutions of NSAIDs that afford better tissue penetration have recently been developed. In ophthalmological practice, topical NSAIDs are mostly used to stabilize pupillary dilation during intraocular surgery, manage postoperative pain and inflammation, and treat pseudophakic cystoid macular edema.Areas covered: This review focuses on the vitreous penetration of topical NSAIDs and their potential clinical applications in the treatment of retinal diseases.Expert opinion: A growing body of evidence suggests that NSAIDs may be beneficial in the treatment of age-related macular degeneration, diabetic retinopathy, and ocular tumors. Recent studies from our group and other authors have shown that the vitreous levels of NSAID exceed the median inhibitory concentration, which can significantly decrease vitreous PGE(2) levels.
C1 [Semeraro, Francesco; Russo, Andrea; Gambicorti, Elena; Duse, Sarah; Morescalchi, Francesco] Univ Brescia, Dept Med & Surg Specialties, Radiol Specialties & Publ Hlth, Ophthalmol Clin, Brescia, Italy.
   [Vezzoli, Sara] Univ Brescia, Dept Med & Surg Specialties, Radiol Specialties & Publ Hlth, Forens Med, Brescia, Italy.
   [Costagliola, Ciro] Univ Molise, Dept Med & Hlth Sci, Campobasso, Italy.
   [Costagliola, Ciro] IRCCS Neuromed, Pozzilli, Isernia, Italy.
C3 University of Brescia; University of Brescia; University of Molise;
   IRCCS Neuromed
RP Russo, A (通讯作者)，Univ Brescia, Dept Med & Surg Specialties, Radiol Specialties & Publ Hlth, Ophthalmol Clin, Brescia, Italy.
EM dott.andrea.russo@gmail.com
RI Costagliola, Ciro/G-5707-2012; Semeraro, Francesco fs/K-8667-2016
OI Costagliola, Ciro/0000-0001-8477-6188; Semeraro, Francesco
   fs/0000-0002-2275-4917
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NR 140
TC 15
Z9 15
U1 3
U2 14
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1742-5247
EI 1744-7593
J9 EXPERT OPIN DRUG DEL
JI Expert Opin. Drug Deliv.
PD NOV 2
PY 2015
VL 12
IS 11
BP 1767
EP 1782
DI 10.1517/17425247.2015.1068756
PG 16
WC Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy
GA DC6OK
UT WOS:000369339200001
PM 26173446
DA 2022-11-30
ER

PT J
AU Cacciamani, A
   Oddone, F
   Parravano, M
   Scarinci, F
   Di Nicola, M
   Lofoco, G
AF Cacciamani, Andrea
   Oddone, Francesco
   Parravano, Mariacristina
   Scarinci, Fabio
   Di Nicola, Marta
   Lofoco, Giorgio
TI Intravitreal injection of bevacizumab: changes in intraocular pressure
   related to ocular axial length
SO JAPANESE JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE Intraocular drugs; Intraocular pressure; Intravitreal injection
ID MACULAR DEGENERATION; PEGAPTANIB; RIGIDITY; AVASTIN
AB To evaluate the immediate and short-term effects of intravitreal injection of 1.25 mg/0.05 ml of bevacizumab on intraocular pressure related to different ocular axial lengths.
   A prospective case series of consecutive patients referred to the Department of Ophthalmology, San Pietro-Fatebenefratelli Hospital, from September 2011 through January 2011.
   Twenty-five patients (10 men and 15 women, mean age 70.2 +/- A 8.98 years) scheduled for intravitreal injection of bevacizumab for the treatment of neovascular age-related macular degeneration were enrolled in this study. Axial length was measured preoperatively using IOLMaster. Intraocular pressure was measured before injection, after 1 min and after 15 min using Tono-Pen XL tonometry.
   The mean intraocular pressure change following the intravitreal bevacizumab injection was 21.92 +/- A 6.95 mmHg after 1 min and 6.24 +/- A 3.77 mmHg after 15 min. The mean axial length of the examined eyes was 23.2 +/- A 1.06 mm. A good correlation was observed between the axial length and intraocular pressure rise after both 1 (R (2) = 0.752, p < 0.001) and 15 min (R (2) = 0.559, p < 0.001).
   Patients undergoing intravitreal injection of 0.05 ml of bevacizumab can be exposed to intraocular pressure increases correlated to ocular axial length.
C1 [Cacciamani, Andrea; Oddone, Francesco; Parravano, Mariacristina; Scarinci, Fabio] IRCCS, Fdn GB Bietti, I-00198 Rome, Italy.
   [Di Nicola, Marta] Univ G dAnnunzio, Dept Biomed Sci, Lab Biostat, Chieti Pescara, Italy.
   [Lofoco, Giorgio] Osped Fatebenefratelli San Pietro, Rome, Italy.
C3 IRCCS - Fondazione "G.B. Bietti" per lo Studio e la Ricerca in
   Oftalmologia; G d'Annunzio University of Chieti-Pescara
RP Scarinci, F (通讯作者)，IRCCS, Fdn GB Bietti, Via Livenza 3-5, I-00198 Rome, Italy.
EM fabioscarinci@gmail.com
RI Oddone, Francesco/K-8876-2016; Scarinci, Fabio/AAB-5126-2020;
   Cacciamani, Andrea/AAB-2154-2021
OI Oddone, Francesco/0000-0002-2504-0004; Cacciamani,
   Andrea/0000-0003-1793-9842; DI NICOLA, MARTA/0000-0003-1748-1931;
   Scarinci, Fabio/0000-0001-5444-4377
CR [Anonymous], 2006, GUID PERF INTR THER
   Avery RL, 2006, OPHTHALMOLOGY, V113, P363, DOI 10.1016/j.ophtha.2005.11.019
   Bakri SJ, 2009, EYE, V23, P181, DOI 10.1038/sj.eye.6702938
   Boon CJF, 2008, OPHTHALMOLOGY, V115, P1268, DOI 10.1016/j.ophtha.2008.02.021
   Falkenstein IA, 2007, RETINA-J RET VIT DIS, V27, P1044, DOI 10.1097/IAE.0b013e3180592ba6
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NR 22
TC 22
Z9 22
U1 0
U2 2
PU SPRINGER JAPAN KK
PI TOKYO
PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065,
   JAPAN
SN 0021-5155
EI 1613-2246
J9 JPN J OPHTHALMOL
JI Jpn. J. Ophthalmol.
PD JAN
PY 2013
VL 57
IS 1
BP 63
EP 67
DI 10.1007/s10384-012-0194-8
PG 5
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 070FS
UT WOS:000313492200007
PM 23093311
DA 2022-11-30
ER

PT J
AU Zambelli-Weiner, A
   Crews, JE
   Friedman, DS
AF Zambelli-Weiner, April
   Crews, John E.
   Friedman, David S.
TI Disparities in Adult Vision Health in the United States
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID OPEN-ANGLE GLAUCOMA; REPORTED VISUAL IMPAIRMENT; ANGELES LATINO EYE;
   RISK-FACTORS; DIABETIC-RETINOPATHY; OLDER-ADULTS; MACULAR DEGENERATION;
   REFRACTIVE ERROR; NATIONAL-HEALTH; SEE PROJECT
AB PURPOSE: To review the existing knowledge on vision health disparities in major adult vision health outcomes (age-related macular degeneration, diabetic retinopathy, glaucoma, cataract, refractive errors) and visual impairment and to identify knowledge gaps as related to the development of enhanced vision health surveillance in the United States.
   DESIGN: Literature review.
   METHODS: Analysis of relevant publications in the peer-reviewed literature.
   RESULTS: Prevalence data on vision health outcomes is limited to findings from a few key population-based studies. Study populations are not representative of all persons living in the United States. Vision loss and visual impairment are more common with age, and there is racial variation in the specific causes of vision loss (underlying health conditions). Women are at greater risk of vision loss than men (even after adjusting for age). Vision-related disability and disparities in visual outcomes are monitored poorly at present.
   CONCLUSIONS: Data to assess and monitor trends in vision health disparities in the United States are not collected presently in a systematic fashion. This lack of data limits public health efforts to overcome barriers to eye care use and to improve vision outcomes. (Am J Ophthalmol 2012;154:S23-S30. 2012 by Elsevier Inc. All rights reserved.)
C1 [Zambelli-Weiner, April] Epidemiol Int, Hunt Valley, MD USA.
   [Crews, John E.] Ctr Dis Control & Prevent, Vis Hlth Initiat, Div Diabet Translat, Atlanta, GA USA.
   [Friedman, David S.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA.
C3 Centers for Disease Control & Prevention - USA; Johns Hopkins
   University; Johns Hopkins Medicine
RP Zambelli-Weiner, A (通讯作者)，Translat Technol Int, 304 Piedmont St, Hampstead, MD 21074 USA.
EM aweiner@transtechint.com
OI Friedman, David/0000-0002-2055-5797
FU CDC Vision Health Initiative, Atlanta, Georgia
FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE
   OF POTENTIAL CONFLICTS OF Interest and the following were reported. Dr
   Friedman is a consultant to Alcon, Allergan, Bausch & Lomb, Merck,
   Pfizer, QLT, Inc, and Epidemiology International, Inc. Publication of
   this article was supported by the CDC Vision Health Initiative, Atlanta,
   Georgia. Involved in Design of study (A.Z.-W., J.E.C., D.S.F.); Conduct
   of study (A.Z.-W., D.S.F.); Collection, management, analysis, and
   interpretation of data (A.Z.-W., J.E.C., D.S.F.); and Preparation,
   review, and approval of manuscript (A.Z.-W., J.E.C., D.S.F.). This
   article represents a literature review and no human subjects were
   involved. The authors thank Susan Carlson, Chief Operating Officer, A+
   Government Solutions, Inc, and the A+ staff for project management and
   publication support. The findings and conclusions in this paper are
   those of the authors and do not necessarily represent the official
   position of the Centers for Disease Control and Prevention.
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NR 63
TC 55
Z9 55
U1 0
U2 21
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD DEC
PY 2012
VL 154
IS 6
SU S
BP S23
EP S30
DI 10.1016/j.ajo.2012.03.018
PG 8
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)
SC Ophthalmology
GA 047ZC
UT WOS:000311879000004
PM 22633355
DA 2022-11-30
ER

PT J
AU Abarrategui-Garrido, C
   Martinez-Barricarte, R
   Lopez-Trascasa, M
   de Cordoba, SR
   Sanchez-Corral, P
AF Abarrategui-Garrido, Cynthia
   Martinez-Barricarte, Ruben
   Lopez-Trascasa, Margarita
   Rodriguez de Cordoba, Santiago
   Sanchez-Corral, Pilar
TI Characterization of complement factor H-related (CFHR) proteins in
   plasma reveals novel genetic variations of CFHR1 associated with
   atypical hemolytic uremic syndrome
SO BLOOD
LA English
DT Article
ID DISEASE ASSOCIATIONS; MACULAR DEGENERATION; FAMILY; AUTOANTIBODIES;
   HEPARIN; C3B; DEFICIENCY; MUTATIONS; BINDING; REGION
AB The factor H-related protein family (CFHR) is a group of minor plasma proteins genetically and structurally related to complement factor H (fH). Notably, deficiency of CFHR1/CFHR3 associates with protection against age-related macular degeneration and with the presence of anti-fH autoantibodies in atypical hemolytic uremic syndrome (aHUS). We have developed a proteomics strategy to analyze the CFHR proteins in plasma samples from controls, patients with aHUS, and patients with type II membranoproliferative glomerulonephritis. Here, we report on the identification of persons carrying novel deficiencies of CFHR1, CFHR3, and CFHR1/CFHR4A, resulting from point mutations in CFHR1 and CFHR3 or from a rearrangement involving CFHR1 and CFHR4. Remarkably, patients with aHUS lacking CFHR1, but not those lacking CFHR3, present anti-fH autoantibodies, suggesting that generation of these antibodies is specifically related to CFHR1 deficiency. We also report the characterization of a novel CFHR1 polymorphism, resulting from a gene conversion event between CFH and CFHR1, which strongly associates with aHUS. The risk allotype CFHR1*B, with greater sequence similarity to fH, may compete with fH, decreasing protection of cellular surfaces against complement damage. In summary, our comprehensive analyses of the CFHR proteins have improved our understanding of these proteins and provided further insights into aHUS pathogenesis. (Blood. 2009; 114: 4261-4271)
C1 [Abarrategui-Garrido, Cynthia; Sanchez-Corral, Pilar] Hosp Univ La Paz, Res Unit, Madrid 28046, Spain.
   [Martinez-Barricarte, Ruben; Rodriguez de Cordoba, Santiago] CSIC, Ctr Invest Biol, Ctr Invest Biomed Red Enfermedades Raras, Madrid, Spain.
   [Martinez-Barricarte, Ruben; Rodriguez de Cordoba, Santiago] Inst Reina Sofia Invest Nefrol, Madrid, Spain.
   [Lopez-Trascasa, Margarita] Hosp Univ La Paz, Immunol Unit, Madrid 28046, Spain.
C3 Hospital Universitario La Paz; CIBER - Centro de Investigacion Biomedica
   en Red; CIBERER; Consejo Superior de Investigaciones Cientificas (CSIC);
   CSIC - Centro de Investigaciones Biologicas (CIB); Hospital
   Universitario La Paz
RP Sanchez-Corral, P (通讯作者)，Hosp Univ La Paz, Res Unit, Paseo Castellana 261, Madrid 28046, Spain.
EM psanchez.hulp@salud.madrid.org
RI de Cordoba, Santiago Rodriguez/K-6727-2014; López-Trascasa,
   Margarita/L-2699-2014; Sánchez-Corral, Pilar/GLR-0387-2022; Barricarte,
   Ruben Martinez/W-8695-2019
OI de Cordoba, Santiago Rodriguez/0000-0001-6401-1874; López-Trascasa,
   Margarita/0000-0001-8594-282X; Barricarte, Ruben
   Martinez/0000-0001-7925-449X
FU Spanish Ministerio de Ciencia e Innovacion [FIS 06/0625, SAF 2005-00913,
   SAF 2008-00226, SAF 2006-02948]; CIBER de Enfermedades Raras (CIBERER);
   Fundacion Renal Inigo Alvarez de Toledo; Fundacion para la Investigacion
   Biomedica-Hospital Universitario La Paz
FX We thank Sheila Pinto for excellent technical assistance and Prof Peter
   F. Zipfel (Hans-Knoll Institute, Jena, Germany) and Dr Jennifer McRae
   (St Vincent's Health, Melbourne, Australia) for providing us with
   polyclonal antibodies recognizing CFHR proteins. We also thank Dr Marie
   Agnes Dragon-Durey (Hopital Georges Pompidou, Paris, France) for the
   reference sample containing fH autoantibodies. This work was supported
   by the Spanish Ministerio de Ciencia e Innovacion (grants FIS 06/0625 to
   P.S.-C., SAF 2005-00913 and SAF 2008-00226 to S. R.d.C., SAF 2006-02948
   to M. L. T.) and by grants from the CIBER de Enfermedades Raras
   (CIBERER) and the Fundacion Renal Inigo Alvarez de Toledo. C. A. G. was
   funded by the "Fundacion para la Investigacion Biomedica-Hospital
   Universitario La Paz" (FIBHULP).
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   SWISS PROTEIN DATABA
NR 32
TC 158
Z9 164
U1 0
U2 7
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD NOV 5
PY 2009
VL 114
IS 19
BP 4261
EP 4271
DI 10.1182/blood-2009-05-223834
PG 11
WC Hematology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Hematology
GA 515TJ
UT WOS:000271495500039
PM 19745068
DA 2022-11-30
ER

PT J
AU Debefve, E
   Pegaz, B
   Ballini, JP
   van den Bergh, H
AF Debefve, Elodie
   Pegaz, Bernadette
   Ballini, Jean-Pierre
   van den Bergh, Hubert
TI Combination Therapy Using Verteporfin and Ranibizumab; Optimizing the
   Timing in the CAM Model
SO PHOTOCHEMISTRY AND PHOTOBIOLOGY
LA English
DT Article
ID CHOROIDAL NEOVASCULAR MEMBRANES; ENDOTHELIAL GROWTH-FACTOR; PHOTODYNAMIC
   THERAPY; MACULAR DEGENERATION; INTRAVITREAL TRIAMCINOLONE;
   DRUG-DELIVERY; BEVACIZUMAB; EXPRESSION; INJECTION; VEGF
AB Combining photodynamic therapy (PDT) using verteporfin (Visudyne(R)) with ranibizumab (Lucentis(R)) can optimize the overall treatment outcome by providing more efficacy in vessel closure, and thus reduce the need for retreatment in patients with wet age-related macular degeneration. In this preclinical study in the chorioallantoic membrane (CAM) of the chicken embryo, we compare the vascular occlusion effects of verteporfin and ranibizumab as monotherapies with those observed in the combined therapy. In order to optimize the combination therapy, we varied the timing and sequence of the PDT and antivascular endothelial growth factor modalities. We observed that 1 day after PDT, the smaller blood vessels (null set < 70 mu m) of the CAM were selectively occluded, but as early as 2 days after PDT, both significant reperfusion and regrowth of new vessels were observed. Both these phenomena could be significantly delayed by application of ranibizumab. Ranibizumab itself did not induce any vascular occlusion. Under the applied conditions of combination therapy, the occlusion of the targeted blood vessels could be significantly extended to 3 days in this model compared with 1 day in the case of verteporfin monotherapy. Thus, in the present preclinical study, we demonstrate that for the applied conditions, the optimal time to administer ranibizumab is 24 h after PDT.
C1 [Debefve, Elodie; Pegaz, Bernadette; Ballini, Jean-Pierre; van den Bergh, Hubert] Ecole Polytech Fed Lausanne, Lab Photomed, CH-1015 Lausanne, Switzerland.
C3 Ecole Polytechnique Federale de Lausanne
RP Debefve, E (通讯作者)，Ecole Polytech Fed Lausanne, Lab Photomed, CH-1015 Lausanne, Switzerland.
EM elodie.debefve@ep.ch
FU Novartis
FX The authors are grateful for financial support from Novartis. The main
   drugs used for this study (Visudyne(R) and Lucentis(R)) were also kindly
   provided by Novartis.
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NR 31
TC 12
Z9 12
U1 0
U2 3
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0031-8655
J9 PHOTOCHEM PHOTOBIOL
JI Photochem. Photobiol.
PD NOV-DEC
PY 2009
VL 85
IS 6
BP 1400
EP 1408
DI 10.1111/j.1751-1097.2009.00604.x
PG 9
WC Biochemistry & Molecular Biology; Biophysics
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Biophysics
GA 509UX
UT WOS:000271045200015
PM 19706144
DA 2022-11-30
ER

PT J
AU Weingessel, B
   Sacu, S
   Vecsei-Marlovits, PV
   Weingessel, A
   Richter-Mueksch, S
   Schmidt-Erfurth, U
AF Weingessel, B.
   Sacu, S.
   Vecsei-Marlovits, P. V.
   Weingessel, A.
   Richter-Mueksch, S.
   Schmidt-Erfurth, U.
TI Interexaminer and intraexaminer reliability of the microperimeter MP-1
SO EYE
LA English
DT Article
DE microperimetry; reliability; fixation stability; macular sensitivity
ID SCANNING LASER OPHTHALMOSCOPE; DIABETIC MACULAR EDEMA; OCULAR
   HYPERTENSION TREATMENT; OPTICAL COHERENCE TOMOGRAPHY; TEST-RETEST
   VARIABILITY; FUNDUS PERIMETRY; INTERRATER AGREEMENT; GLAUCOMA;
   REPRODUCIBILITY; THRESHOLD
AB Purpose To evaluate the interexaminer and intraexaminer reliability of macular microperimetry using the microperimeter MP-1.
   Methods Participants: Fifteen healthy volunteers younger than 40 years of age (Group 1), 15 healthy subjects over 60 years (Group 2), and five patients with age-related macular degeneration (Group 3). Observation procedure: Two examiners (E1 and E2) measured, in random order, interexaminer (E2-E1a) reliability. Another examination was undergone by one of the examiners a week later to evaluate the intraexaminer (E1b-E1a) reliability. Main outcome measures: Macular sensitivity (mean threshold (decibel)) and stability of fixation were determined using MP1 microperimetry. Agreement was analysed by means of Bland-Altman plots and by the determination of the intraclass correlation coefficient.
   Results The interexaminer (E2-E1a) and the intraexaminer (E1b-E1a) differences in the mean threshold values were not statistically significant (P = 0.850, 95% confidence Interval (CI) = -0.265 to 0.319; P = 0.246, 95% CI = -0.099 to 0.375, respectively). Limits of agreement and intraclass correlation coefficients also showed good agreement in each group.
   Conclusions A good reliability was found for the mean threshold values in all the three groups, indicating examiner-independent measurements. Eye (2009) 23, 1052-1058; doi:10.1038/eye.2008.237; published online 1 August 2008
C1 [Weingessel, B.; Sacu, S.; Vecsei-Marlovits, P. V.; Richter-Mueksch, S.; Schmidt-Erfurth, U.] Med Univ Vienna, Dept Ophthalmol, A-1090 Vienna, Austria.
   [Weingessel, A.] Univ Technol, Dept Stat & Probabil Theory, Vienna, Austria.
C3 Medical University of Vienna; Technische Universitat Wien
RP Vecsei-Marlovits, PV (通讯作者)，Med Univ Vienna, Dept Ophthalmol, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM veronika.vecseimarlovits@meduniwien.ac.at
RI Weingessel, Birgit/ABD-5201-2021; Weingessel, Birgit/AAM-6617-2021
OI Weingessel, Birgit/0000-0002-1110-0432; 
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NR 40
TC 31
Z9 32
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD MAY
PY 2009
VL 23
IS 5
BP 1052
EP 1058
DI 10.1038/eye.2008.237
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 445AY
UT WOS:000266023200008
PM 18670459
OA Bronze
DA 2022-11-30
ER

PT J
AU Tatar, O
   Shinoda, K
   Kaiserling, E
   Claes, C
   Eckardt, C
   Eckert, T
   Pertile, G
   Boeyden, V
   Scharioth, GB
   Yoeruek, E
   Szurman, P
   Bartz-Schmidt, KU
   Grisanti, S
AF Tatar, O.
   Shinoda, K.
   Kaiserling, E.
   Claes, C.
   Eckardt, C.
   Eckert, T.
   Pertile, G.
   Boeyden, V.
   Scharioth, G. B.
   Yoeruek, E.
   Szurman, P.
   Bartz-Schmidt, K. U.
   Grisanti, S.
CA Tuebingen Bevacizumab Study Grp
TI Implications of bevacizumab on vascular endothelial growth factor and
   endostatin in human choroidal neovascularisation
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID VERTEPORFIN PHOTODYNAMIC THERAPY; INTRAVITREAL BEVACIZUMAB; MACULAR
   DEGENERATION; COLLAGEN-XVIII; EXPRESSION; AVASTIN; ANGIOGENESIS;
   ANGIOSTATIN; MACROPHAGE; INHIBITION
AB Aim: To evaluate the implications of intravitreal bevacizumab on proangiogenic vascular endothelial growth factor (VEGF) with regard to the endogenous angiogenesis inhibitor endostatin in human choroidal neovascularisation (CNV) secondary to age-related macular degeneration.
   Methods: Retrospective review of an interventional case series of 48 patients who underwent full macular translocation surgery with removal of CNV. Twenty-five patients were treated with intravitreal bevacizumab injection 1 to 154 days prior to surgery (bevacizumab CNV). Twenty-three CNV without any kind of previous treatment were used as controls (control CNV). CNV were stained for CD34, cytokeratin 18, VEGF, endostatin and E-selectin. A "predominance score of VEGF over endostatin'' (PS) was defined by the difference between VEGF and endostatin staining scores.
   Results: Bevacizumab CNV revealed a weaker VEGF expression in endothelial cells (p=0.0245) but significantly more intense endostatin in retina pigment epithelium (RPE) (p=0.0001) and stroma (p<0.0001). Consequently, PS was significantly lower in RPE (p=0.02), vessels (p=0.03) and stroma (p=0.0004) in bevacizumab CNV. The intensity of E-selectin expression in bevacizumab CNV was comparable with that in control CNV.
   Conclusions: A shift within the angiogenic balance in terms of decreased VEGF predominance over endostatin is detected in human CNV treated with bevacizumab.
C1 [Grisanti, S.] Med Univ Lubeck, Dept Ophthalmol, D-23538 Lubeck, Germany.
   [Tatar, O.; Yoeruek, E.; Szurman, P.; Bartz-Schmidt, K. U.; Tuebingen Bevacizumab Study Grp] Univ Tubingen, Ctr Ophthalmol, Univ Eye Clin, Tubingen, Germany.
   [Shinoda, K.] Natl Inst Sensory Organs, Lab Visual Physiol, Tokyo, Japan.
   [Kaiserling, E.] Univ Tubingen, Dept Pathol, Tubingen, Germany.
   [Claes, C.; Boeyden, V.] AZ Sint Augustinus Hosp, Dept Achtersegment, Antwerp, Belgium.
   [Eckardt, C.; Eckert, T.] Staedt Kliniken, Augenklin, Frankfurt, Germany.
   [Pertile, G.] Sacro Cuore Hosp, Dept Ophthalmol, Negrar, Italy.
   [Scharioth, G. B.] Augenzentrum Recklinghausen, Recklinghausen, Germany.
C3 University of Lubeck; Eberhard Karls University of Tubingen; Eberhard
   Karls University Hospital; Eberhard Karls University of Tubingen;
   Eberhard Karls University Hospital; University of Hamburg; University
   Medical Center Hamburg-Eppendorf; IRCCS Sacro Cuore Don Calabria
RP Grisanti, S (通讯作者)，Med Univ Lubeck, Dept Ophthalmol, Ratzeburger Allee 160, D-23538 Lubeck, Germany.
EM salvatore.grisanti@uk-sh.de
RI Pertile, Grazia/AAC-4956-2022
FU Vision 100 Foundation; Jung Foundation
FX Grant Support: Vision 100 Foundation and Jung Foundation.
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NR 49
TC 5
Z9 6
U1 0
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD FEB
PY 2009
VL 93
IS 2
BP 159
EP 165
DI 10.1136/bjo.2008.138594
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 399XZ
UT WOS:000262833900007
PM 18838410
DA 2022-11-30
ER

PT J
AU Konstantopoulos, A
   Williams, CPR
   Newsom, RS
   Luff, AJ
AF Konstantopoulos, A.
   Williams, C. P. R.
   Newsom, R. S.
   Luff, A. J.
TI Ocular morbidity associated with intravitreal triamcinolone acetonide
SO EYE
LA English
DT Article
DE intravitreal triamcinolone; complications; intraocular pressure
ID DIABETIC MACULAR EDEMA; INTRAOCULAR-PRESSURE; INJECTION; MANAGEMENT;
   COMPLICATIONS; UVEITIS
AB Aim To report on the complications associated with the use of intravitreal triamcinolone acetonide (IVTA) in a tertiary referral hospital setting.
   Materials and methods A retrospective case series review of all IVTA injections carried out over a period of 30 months.
   Results One hundred and thirty IVTA injections were performed; nine with limited local follow-up were excluded. Thus, 121 injections (108 patients, 114 eyes) were included in the study. Triamcinolone (4 mg) was used in all cases. Indications were diabetic macular oedema (n = 41 eyes), retinal vein occlusions (n = 27), postoperative cystoid macular oedema (n = 24), exudative age-related macular degeneration (n = 16), and others (n = 6). No intraoperative complications were recorded. Postoperative intraocular pressure (IOP) readings of 22, 28, 35, and 40 mmHg or higher were recorded in 46.5, 29.8, 12.3, and 7.9% of eyes, respectively. IOP elevation was treated with antiglaucoma medication in all but one eye (0.9%) that required trabeculectomy and one (0.9%) that required vitrectomy with cataract extraction for suspected phacoanaphylactic glaucoma. Two eyes (1.8%) developed retinal detachment; both had previously been treated for retinal breaks. One eye (0.9%) developed culture-positive endophthalmitis.
   Conclusions Significant morbidity is associated with IVTA injection; clinicians should be aware when considering treatment options.
C1 Southampton Univ Hosp NHS Trust, Southampton Eye Unit, Southampton SO16 6YD, Hants, England.
C3 University of Southampton; University Hospital Southampton NHS
   Foundation Trust
RP Konstantopoulos, A (通讯作者)，Southampton Univ Hosp NHS Trust, Southampton Eye Unit, Tremona Rd, Southampton SO16 6YD, Hants, England.
EM ariskons@yahoo.com
OI newsom, Richard/0000-0002-2221-0653
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NR 22
TC 32
Z9 33
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD MAR
PY 2007
VL 21
IS 3
BP 317
EP 320
DI 10.1038/sj.eye.6702416
PG 4
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 141US
UT WOS:000244604900002
PM 16710433
OA Bronze
DA 2022-11-30
ER

PT J
AU Kaarniranta, K
   Ryhanen, T
   Karjalainen, HM
   Lammi, MJ
   Suuronen, T
   Huhtala, A
   Kontkanen, M
   Terasvirta, M
   Uusitalo, H
   Salminen, A
AF Kaarniranta, K
   Ryhanen, T
   Karjalainen, HM
   Lammi, MJ
   Suuronen, T
   Huhtala, A
   Kontkanen, M
   Terasvirta, M
   Uusitalo, H
   Salminen, A
TI Geldanamycin increases 4-hydroxynonenal (HNE)-induced cell death in
   human retinal pigment epithelial cells
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE geldanamycin; heat shock protein; hydroxynonenal; macular degeneration;
   oxidative stress; retinal pigment epithelial
ID NF-KAPPA-B; SHOCK GENE-EXPRESSION; HEAT-SHOCK; MOLECULAR CHAPERONES;
   TRANSCRIPTION FACTOR; HYDROSTATIC-PRESSURE; MACULAR DEGENERATION;
   CHONDROCYTIC CELLS; OXIDATIVE STRESS; MESSENGER-RNA
AB Development of age-related macular degeneration (AMD) is associated with functional abnormalities and cell death in retinal pigment epithelial (RPE) cells attributable to oxidative stress. To minimize the adverse effects of oxidative stress, cells activate their defence systems, e.g., via increased expression of heat shock protein (Hsp), activation of stress sensitive AP-1 and NF-kappaB transcription factors. In this study, we examined the accumulation of Hsp70 protein, activation of AP-1 and NF-kappaB transcription factors in human ARPE-19 cells subjected to a 4-hydroxynonenal (HNE)-induced oxidative stress. In addition, the influence of Hsp90 inhibitor geldanamycin (GA) was studied in HNE-treated cells. Mitochondrial metabolic activity and apoptosis were determined to evaluate cell death in the ARPE-19 cells. The ARPE-19 cells showed increased accumulation of Hsp70 protein before of the cytotoxic hallmarks appearing in response to HNE. In contrast, increased DNA-binding activities of AP-1 or NF-kappaB transcription factors were not seen under HNE insults. Interestingly, GA significantly increased cell death in the HNE-treated cells, which was involved in caspase-3 independent apoptosis. This study reveals that the Hsps have an important role in the cytoprotection of RPE cells Subjected to HNE-derived oxidative stress. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
C1 Univ Kuopio, Dept Ophthalmol, FIN-70211 Kuopio, Finland.
   Kuopio Univ Hosp, Dept Ophthalmol, Kuopio 70211, Finland.
   Univ Kuopio, Dept Anat, FIN-70211 Kuopio, Finland.
   Univ Kuopio, Dept Neurosci & Neurol, FIN-70211 Kuopio, Finland.
   Univ Tampere, Sch Med, Tampere 33014, Finland.
   N Karelia Cent Hosp, Dept Ophthalmol, Joensuu 80210, Finland.
   Kuopio Univ Hosp, Dept Neurol, Kuopio 70211, Finland.
C3 University of Eastern Finland; Kuopio University Hospital; University of
   Eastern Finland; University of Eastern Finland; University of Eastern
   Finland; Tampere University; Kuopio University Hospital; University of
   Eastern Finland
RP Kaarniranta, K (通讯作者)，Univ Kuopio, Dept Ophthalmol, FIN-70211 Kuopio, Finland.
EM kaarnira@messi.uku.fi
RI Lammi, Mikko/B-9291-2008
OI Lammi, Mikko/0000-0002-6181-9904; Huhtala, Anne/0000-0001-7862-3564;
   Kaarniranta, Kai/0000-0003-2600-8679
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NR 33
TC 42
Z9 43
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0304-3940
EI 1872-7972
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD JUL 1
PY 2005
VL 382
IS 1-2
BP 185
EP 190
DI 10.1016/j.neulet.2005.03.009
PG 6
WC Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Neurosciences & Neurology
GA 933VV
UT WOS:000229661900036
PM 15911146
DA 2022-11-30
ER

PT J
AU Bora, PS
   Sohn, JH
   Cruz, JMC
   Jha, P
   Nishihori, H
   Wang, Y
   Kaliappan, S
   Kaplan, HJ
   Bora, NS
AF Bora, PS
   Sohn, JH
   Cruz, JMC
   Jha, P
   Nishihori, H
   Wang, Y
   Kaliappan, S
   Kaplan, HJ
   Bora, NS
TI Role of complement and complement membrane attack complex in
   laser-induced choroidal neovascularization
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID FIBROBLAST GROWTH-FACTOR; MACULAR DEGENERATION; SUBRETINAL
   NEOVASCULARIZATION; FACTOR EXPRESSION; MESSENGER-RNA; RISK-FACTORS;
   MOUSE MODEL; ANTIBODY; C5B-9; ANGIOGENESIS
AB Choroidal neovascularization (CNV), or choroidal angiogenesis, is the hallmark of age-related macular degeneration and a leading cause of visual loss after age 55. The pathogenesis of new choroidal vessel formation is poorly understood. Although inflammation has been implicated in the development of CNV, the role of complement in CNV has not been explored experimentally. A reliable way to produce CNV in animals is to rupture Bruch's membrane with laser photocoagulation. A murine model of laser-induced CNV in C57BL/6 mice revealed the deposition of C3 and membrane attack complex (MAC) in the neovascular complex. CNV was inhibited by complement depletion using cobra venom factor and did not develop in C3(-/-) mice. Anti-murine C6 Abs in C57BL/6 mice inhibited MAC formation and also resulted in the inhibition of CNV. Vascular endothelial growth factor, TGF-beta2,. and beta-fibroblast growth factor were elevated in C57BL/6 mice after laser-induced CNV; complement depletion resulted in a marked reduction in the level of these angiogenic factors. Thus, activation of complement, specifically the formation of MAC, is essential for the development of laser- induced choroidal angiogenesis in mice. It is possible that a similar mechanism may be involved in the pathophysiology of other angiogenesis essential diseases.
C1 Univ Louisville, Dept Ophthalmol & Visual Sci, Kentucky Lions Eye Ctr, Louisville, KY 40202 USA.
C3 University of Louisville
RP Bora, PS (通讯作者)，Univ Louisville, Dept Ophthalmol & Visual Sci, Kentucky Lions Eye Ctr, 301E Muhammad Ali Blvd, Louisville, KY 40202 USA.
EM psbora01@louisville.edu
RI Mohammed, Imran/J-8271-2012
OI Mohammed, Imran/0000-0002-8412-0768; Bora, Puran/0000-0003-4781-1217
FU NATIONAL EYE INSTITUTE [R01EY013335, R01EY009730, R01EY014623] Funding
   Source: NIH RePORTER; NEI NIH HHS [R01 EY013335-03, EY 13335, R01
   EY009730-07, EY 014623] Funding Source: Medline
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NR 51
TC 201
Z9 252
U1 0
U2 6
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 JAN 1
PY 2005
VL 174
IS 1
BP 491
EP 497
DI 10.4049/jimmunol.174.1.491
PG 7
WC Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Immunology
GA 881HB
UT WOS:000225852900057
PM 15611275
OA Bronze
DA 2022-11-30
ER

PT J
AU Ergun, E
   Zawinka, C
   Stur, M
AF Ergun, E
   Zawinka, C
   Stur, M
TI Incidence of laser photocoagulation and photodynamic therapy with
   verteporfin at a tertiary retinal center
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; OCULAR HISTOPLASMOSIS SYNDROME;
   EXTERNAL-BEAM RADIOTHERAPY; MACULAR DEGENERATION; TRANSPUPILLARY
   THERMOTHERAPY; RADIATION-THERAPY; SURGICAL REMOVAL; TRANSPLANTATION;
   SURGERY
AB Purpose: To examine the influence of photodynamic therapy (PDT) with verteporfin on the indication and frequency of conventional thermal krypton laser photocoagulation in choroidal neovascularization.
   Methods: A retrospective chart review was performed comparing laser indication and frequency 1 year before and 2 years after PDT started to be used routinely following the guidelines of the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy Study Group and the Verteporfin in Photodynamic Therapy Study Group.
   Results: Similar frequencies of laser treatment were seen in the year before and during the first year after PDT was commenced (301 [7.1% of all patients] to 281 [6.9%]). In the year thereafter, however, there was a marked decrease in laser treatments (1174 [3.9%]). Interestingly, there was a steady increase in the relative frequency of laser treatments of extrafoveal and parapapillary lesions in the years after PDT was commenced (29.2%, year 1; 30.6%, year 2; and 39.6%, year 3).
   Conclusion: PDT has led to a decrease in conventional laser photocoagulation at one large tertiary retinal center in Austria. Moreover, it is our belief that patients are now referred at earlier stages of the disease, which has resulted in a shift in thermal laser indications.
C1 Univ Vienna, Sch Med, Dept Ophthalmol, A-1090 Vienna, Austria.
C3 University of Vienna
RP Ergun, E (通讯作者)，Univ Vienna, Sch Med, Dept Ophthalmol, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM erdem.ergun@akh-wien.ac.at
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NR 36
TC 4
Z9 4
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 FEB
PY 2004
VL 24
IS 1
BP 13
EP 18
DI 10.1097/00006982-200402000-00002
PG 6
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 778HU
UT WOS:000189234200002
PM 15076938
DA 2022-11-30
ER

PT J
AU Losso, JN
AF Losso, JN
TI Targeting excessive angiogenesis with functional foods and
   nutraceuticals
SO TRENDS IN FOOD SCIENCE & TECHNOLOGY
LA English
DT Review
ID CONVERTING-ENZYME INHIBITORS; SODIUM PHENYLACETATE NAPA; NITRIC-OXIDE
   SYNTHASE; GREEN TEA CATECHINS; TUMOR-GROWTH; ENDOTHELIAL-CELLS;
   HEPATOCELLULAR-CARCINOMA; IN-VITRO; CANCER; EXPRESSION
AB Interest in angiogenesis as a target for degenerative diseases prevention and/or therapy has resulted from the gradual recognition that angiogenesis is a hallmark of-and pivotal for the spread of-almost all neoplastic and non-neoplastic degenerative diseases including cancer, diabetes, chronic inflammation, arthritis, age-related macular degeneration, Alzheimers, psoriasis, restenosis, and many more. Angiogenesis is a dynamic, complex, multistep enzymatic process which involves almost all classes of enzymes and includes positive and negative regulators. Since angiogenesis is a process that is generally down regulated in healthy individuals, targeting of angiogenesis with safe anti-angiogenic compounds, that are selective against newly formed vessels while sparing existing ones, may not lead to side effects even after prolonged exposure. Many inhibitors of angiogenesis are being isolated from functional foods. The rationale of investigating functional foods as anti-angiogenic compounds for degenerative disease prevention is that data from cell cultures and animal models show that these compounds can be safe, effective, reversible inhibitors, ingested appropriately over a life span without severe toxicity, amenable to clinical trials, and possibly become low cost budget prescription. This review demonstrates that enzyme inhibition is the major molecular basis of antiangiogenic functional foods and highlights their potentials and challenges. (C) 2003 Elsevier Ltd. All rights reserved.
C1 Louisiana State Univ, Food Prot Biotechnol Lab, Dept Food Sci, Ctr Agr, Baton Rouge, LA 70803 USA.
C3 Louisiana State University System; Louisiana State University
RP Losso, JN (通讯作者)，Louisiana State Univ, Food Prot Biotechnol Lab, Dept Food Sci, Ctr Agr, 111 Food Sci Bldg, Baton Rouge, LA 70803 USA.
EM jlosso@lsu.edu
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NR 99
TC 30
Z9 34
U1 1
U2 10
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0924-2244
J9 TRENDS FOOD SCI TECH
JI Trends Food Sci. Technol.
PD NOV
PY 2003
VL 14
IS 11
BP 455
EP 468
DI 10.1016/S0924-2244(03)00156-0
PG 14
WC Food Science & Technology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Food Science & Technology
GA 741TE
UT WOS:000186474900002
DA 2022-11-30
ER

PT J
AU Bikbov, MM
   Kazakbaeva, GM
   Rakhimova, EM
   Rusakova, IA
   Fakhretdinova, AA
   Tuliakova, AM
   Panda-Jonas, S
   Gilmanshin, TR
   Zainullin, RM
   Bolshakova, NI
   Safiullina, KR
   Gizzatov, AV
   Ponomarev, IP
   Yakupova, DF
   Baymukhametov, NE
   Nikitin, NA
   Jonas, JB
AF Bikbov, Mukharram M.
   Kazakbaeva, Gyulli M.
   Rakhimova, Ellina M.
   Rusakova, Iuliia A.
   Fakhretdinova, Albina A.
   Tuliakova, Azaliia M.
   Panda-Jonas, Songhomitra
   Gilmanshin, Timur R.
   Zainullin, Rinat M.
   Bolshakova, Natalia, I
   Safiullina, Kamilia R.
   Gizzatov, Ainur, V
   Ponomarev, Ildar P.
   Yakupova, Dilya F.
   Baymukhametov, Nail E.
   Nikitin, Nikolay A.
   Jonas, Jost B.
TI Prevalence Factors Associated With Vision Impairment and Blindness Among
   Individuals 85 Years and Older in Russia
SO JAMA NETWORK OPEN
LA English
DT Article
ID VISUAL IMPAIRMENT; CLASSIFICATION; POPULATION; URBAN; EYE
AB IMPORTANCE Visual performance is important for quality of life. However, vision impairment among adults 85 years and older has not been intensively examined.
   OBJECTIVE To assess the prevalence of mild vision impairment (VI), moderate to severe vision impairment, and blindness and the factors associated with these conditions among a population 85 years and older.
   DESIGN, SETTING, AND PARTICIPANTS The Ural Very Old Study was a population-based cohort study conducted in rural and urban areas in Bashkortostan, Russia from 2017 to 2020. Among 1882 eligible individuals 85 years and older, 1526 participants (81.1%) were enrolled.
   EXPOSURES Ophthalmologic, physical, and mental examinations. Main Outcomes and Measures Prevalence of vision impairment and blindness based on best-corrected visual acuity (BCVA; measured using modified Early Treatment of Diabetic Retinopathy Study charts) in the better eye or both eyes. Mild vision impairment was defined as BCVA worse than 6/12 to 6/18, and moderate to severe VI was defined as BCVA worse than 6/18 but equal to or better than 3/60. Blindness was defined as BCVA worse than 3/60.
   RESULTS Among 1526 participants, 1149 individuals (75.3%; 846 women [73.6%]; mean [SD] age, 88.2 [2.8 years]) had available BCVA measurements and were included in the present analysis. Mild vision impairment was present in 114 individuals (9.9%; 95% CI, 8.2%-11.7%), moderate to severe VI in 562 individuals (48.9%; 95% CI, 46.0%-51.8%), and blindness in 68 individuals (5.9%; 95% CI, 4.6%-7.3%). Factors associated with moderate to severe VI were cataracts (324 individuals [57.7% of those with moderate to severe VI and 28.2% of total population; 95% CI, 25.6%-30.8%]), secondary cataracts (4 individuals [0.7% of those with moderate to severe VI and 0.3% of total population; 95% CI, 0%-0.7%]), age-related macular degeneration (78 individuals [13.9% of those with moderate to severe VI and 6.8% of total population; 95% CI, 5.3%-8.3%]), glaucoma (45 individuals [8.0% of those with moderate to severe VI and 3.9% of total population; 95% CI, 2.8%-5.0%]), corneal opacifications (26 individuals [4.6% of those with moderate to severe VI and 2.3% of total population; 95% CI, 1.4%-3.1%]), myopic maculopathy (13 individuals [2.3% of those with moderate to severe VI and 1.1% of total population; 95% CI, 0.5%-1.7%]), and nonglaucomatous optic nerve damage (4 individuals [0.7% of those with moderate to severe VI and 0.3% of total population; 95% CI, 0%-0.7%]). Factors associated with blindness were cataracts (33 individuals [48.5% of those with blindness and 2.9% of total population; 95% CI, 1.9%-3.8%]), age-related macular degeneration (15 individuals [22.1% of those with blindness and 1.3% of total population; 95% CI, 0.7%-2.0%]), glaucoma (7 individuals [10.3% of those with blindness and 0.6% of total population; 95% CI, 0.2%-1.1%]), myopic maculopathy (3 individuals [4.4% of those with blindness and 0.3% of total population; 95% CI, 0%-0.6%]), and corneal opacifications (2 individuals [2.9% of those with blindness and 0.2% of total population; 95% CI, 0%-0.4%]). Higher moderate to severe VI prevalence was associated with older age (odds ratio [OR], 1.19; 95% CI, 1.11-1.28; P < .001), higher blood pressure (OR, 1.01; 95% CI, 1.00-1.02; P = .03), lower hand grip force (OR, 0.88; 95% CI, 0.83-0.95; P < .001), lower score on the Mini-Mental State Examination (OR, 0.95; 95% CI, 0.92-0.98; P < .001), lower prothrombin index (OR, 0.93; 95% CI, 0.89-0.97; P < .001), lower refractive error (OR, 0.91; 95% CI, 0.85-0.97; P = .006), and lower prevalence of previous cataract surgery (OR, 0.48; 95% CI, 0.33-0.68; P < .001).
   CONCLUSIONS AND RELEVANCE In this cohort study of individuals 85 years and older, the prevalence of moderate to severe VI and blindness was relatively high. Cataracts were the main reversible condition associated with vision loss, and age-related macular degeneration, glaucoma, and myopic maculopathy were the main irreversible conditions. Because a higher prevalence of moderate to severe VI was associated with lower cognitive function and physical strength, improvement of vision through increases in cataract surgery and measures to prevent and treat irreversible conditions may help to improve cognitive function and physical strength.
C1 [Bikbov, Mukharram M.; Kazakbaeva, Gyulli M.; Rakhimova, Ellina M.; Rusakova, Iuliia A.; Fakhretdinova, Albina A.; Tuliakova, Azaliia M.; Gilmanshin, Timur R.; Zainullin, Rinat M.; Bolshakova, Natalia, I; Safiullina, Kamilia R.; Gizzatov, Ainur, V; Ponomarev, Ildar P.; Yakupova, Dilya F.; Baymukhametov, Nail E.; Nikitin, Nikolay A.] Ufa Eye Res Inst, 90 Pushkin St, Ufa 450008, Bashkortostan, Russia.
   [Jonas, Jost B.] Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, Theodor Kutzerufer 1, D-68167 Mannheim, Germany.
   [Panda-Jonas, Songhomitra] Privatpraxis Jonas & Panda Jonas, Heidelberg, Germany.
   [Jonas, Jost B.] Inst Mol & Clin Ophthalmol, Basel, Switzerland.
C3 Ufa Eye Research Institute; Ruprecht Karls University Heidelberg
RP Bikbov, MM (通讯作者)，Ufa Eye Res Inst, 90 Pushkin St, Ufa 450008, Bashkortostan, Russia.; Jonas, JB (通讯作者)，Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, Theodor Kutzerufer 1, D-68167 Mannheim, Germany.
EM bikbov.m@gmail.com; jost.jonas@medma.uni-heidelberg.de
RI Bikbov, Mukharram/AAO-7624-2021; Zainullin, Rinat/AAR-6362-2021
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NR 32
TC 5
Z9 5
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2574-3805
J9 JAMA NETW OPEN
JI JAMA Netw. Open
PD AUG 17
PY 2021
VL 4
IS 8
AR e2121138
DI 10.1001/jamanetworkopen.2021.21138
PG 12
WC Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC General & Internal Medicine
GA UC7WO
UT WOS:000686734600003
PM 34402890
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Regha, K
   Bhargava, M
   Al-Mubaarak, A
   Chai, C
   Parikh, BH
   Liu, ZP
   Wong, CSW
   Hunziker, W
   Lim, KL
   Su, XY
AF Regha, Kakkad
   Bhargava, Mayuri
   Al-Mubaarak, Abdurrahmaan
   Chai, Chou
   Parikh, Bhav Harshad
   Liu, Zengping
   Wong, Claudine See Wei
   Hunziker, Walter
   Lim, Kah Leong
   Su, Xinyi
TI Customized strategies for high-yield purification of retinal pigment
   epithelial cells differentiated from different stem cell sources
SO SCIENTIFIC REPORTS
LA English
DT Article
ID RPE
AB Retinal pigment epithelial (RPE) cell dysfunction and death are characteristics of age-related macular degeneration. A promising therapeutic option is RPE cell transplantation. Development of clinical grade stem-cell derived RPE requires efficient in vitro differentiation and purification methods. Enzymatic purification of RPE relies on the relative adherence of RPE and non-RPE cells to the culture plate. However, morphology and adherence of non-RPE cells differ for different stem cell sources. In cases whereby the non-RPE adhered as strongly as RPE cells to the culture plate, enzymatic method of purification is unsuitable. Thus, we hypothesized the need to customize purification strategies for RPE derived from different stem cell sources. We systematically compared five different RPE purification methods, including manual, enzymatic, flow cytometry-based sorting or combinations thereof for parameters including cell throughput, yield, purity and functionality. Flow cytometry-based approach was suitable for RPE isolation from heterogeneous cultures with highly adherent non-RPE cells, albeit with lower yield. Although all five purification methods generated pure and functional RPE, there were significant differences in yield and processing times. Based on the high purity of the resulting RPE and relatively short processing time, we conclude that a combination of enzymatic and manual purification is ideal for clinical applications.
C1 [Regha, Kakkad; Bhargava, Mayuri; Al-Mubaarak, Abdurrahmaan; Parikh, Bhav Harshad; Liu, Zengping; Wong, Claudine See Wei; Hunziker, Walter; Su, Xinyi] ASTAR, Inst Mol & Cell Biol IMCB, Singapore 138673, Singapore.
   [Regha, Kakkad; Al-Mubaarak, Abdurrahmaan; Liu, Zengping; Su, Xinyi] Natl Univ Singapore NUS, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117597, Singapore.
   [Bhargava, Mayuri; Su, Xinyi] Natl Univ Hosp NUH, Dept Ophthalmol, Singapore 119074, Singapore.
   [Chai, Chou; Lim, Kah Leong] Nanyang Technol Univ NTU, Lee Kong Chian Sch Med, Singapore 308232, Singapore.
   [Liu, Zengping; Su, Xinyi] Singapore Eye Res Inst SERI, Singapore 169856, Singapore.
   [Hunziker, Walter] Natl Univ Singapore NUS, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117593, Singapore.
C3 Agency for Science Technology & Research (A*STAR); A*STAR - Institute of
   Molecular & Cell Biology (IMCB); National University of Singapore;
   Nanyang Technological University & National Institute of Education (NIE)
   Singapore; Nanyang Technological University; National University of
   Singapore
RP Su, XY (通讯作者)，ASTAR, Inst Mol & Cell Biol IMCB, Singapore 138673, Singapore.; Su, XY (通讯作者)，Natl Univ Singapore NUS, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117597, Singapore.; Su, XY (通讯作者)，Natl Univ Hosp NUH, Dept Ophthalmol, Singapore 119074, Singapore.; Su, XY (通讯作者)，Singapore Eye Res Inst SERI, Singapore 169856, Singapore.
EM xysu@imcb.a-star.edu.sg
RI Hunziker, Walter/GSM-8190-2022
OI Al-Mubaarak, Abdurrahmaan/0000-0001-6390-948X
FU National Research Foundation (NRF), Singapore, under its Competitive
   Research Program (CRP) [NRF-CRP21-2018-0008]; Ministry of Education
   (MOE) [MOET32020-0001]
FX We thank Timothy A. Blenkinsop, PhD, Icahn School of Medicine at Mount
   Sinai (New York, USA) for H9 ESC and Boon Seng Soh, PhD, Institute of
   Molecular and Cell Biology (IMCB, Singapore) for H1 ESC. We are thankful
   to Central Imaging Facility at IMCB for providing microscope resources
   and Singapore Immunology Network (SIgN, Singapore) Flow Platform for
   flow cytometry. We thank CellResearch Corporation Pte Ltd for providing
   asF5 dermal fibroblasts. This study was supported by National Research
   Foundation (NRF), Singapore, under its Competitive Research Program
   (CRP) [NRF-CRP21-2018-0008] and Ministry of Education (MOE) for its MOE
   Academic Research Fund Tier 3 (STEM) [MOET32020-0001].
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NR 34
TC 0
Z9 0
U1 0
U2 0
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD SEP 16
PY 2022
VL 12
IS 1
AR 15563
DI 10.1038/s41598-022-19777-2
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA 4O6GX
UT WOS:000854795000014
PM 36114268
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Corvi, F
   Corradetti, G
   Nittala, MG
   Velaga, SB
   Haines, JL
   Pericak-Vance, MA
   Stambolian, D
   Sadda, SR
AF Corvi, Federico
   Corradetti, Giulia
   Nittala, Muneeswar Gupta
   Velaga, Swetha Bindu
   Haines, Jonathan L.
   Pericak-Vance, Margaret Ann
   Stambolian, Dwight
   Sadda, SriniVas R.
TI COMPARISON OF SPECTRALIS AND CIRRUS OPTICAL COHERENCE TOMOGRAPHY FOR THE
   DETECTION OF INCOMPLETE AND COMPLETE RETINAL PIGMENT EPITHELIUM AND
   OUTER RETINAL ATROPHY
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; Cirrus; complete retinal pigment
   epithelial and outer retinal atrophy; incomplete retinal pigment
   epithelial and outer retinal atrophy; optical coherence tomography;
   Spectralis
ID MACULAR THICKNESS MEASUREMENTS; OCT; DOMAIN; EYES; SEGMENTATION
AB Purpose: To evaluate and compare the detection of incomplete and complete retinal pigment epithelial and outer retinal atrophy (iRORA and cRORA) using Spectralis and Cirrus optical coherence tomography (OCT) devices. Methods: Subjects with late age-related macular degeneration were imaged on the same day with Spectralis and Cirrus OCT. Two, masked, independent, and experienced retina specialist graders evaluated each case for the presence of cRORA and iRORA lesions. Results: A significantly higher number of lesions were observed using Spectralis compared with Cirrus (239 vs. 226 and 223 vs. 209). Higher number of iRORA lesions were identified with Spectralis (105 vs. 90 and 96 vs. 82), and no significant difference was observed between devices for cRORA lesions (134 vs. 136 and 128 vs. 126). When considering the presence or absence of iRORA or cRORA, the agreement between devices for both graders was excellent for cRORA and good for iRORA. Conclusion: Spectralis and Cirrus OCT identified a similar number of cRORA lesions, although more iRORA lesions could be detected with Spectralis OCT. These findings may have implications for developing acquisition protocols for trials based on the intended atrophy targets and highlight the importance of using a consistent OCT instrument across a study.
C1 [Corvi, Federico; Corradetti, Giulia; Nittala, Muneeswar Gupta; Velaga, Swetha Bindu; Sadda, SriniVas R.] Univ Calif Los Angeles, Doheny Eye Inst, Los Angeles, CA 90033 USA.
   [Corvi, Federico; Corradetti, Giulia; Sadda, SriniVas R.] UCLA, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90033 USA.
   [Corvi, Federico] Univ Milan, Sacco Hosp, Dept Biomed & Clin Sci Luigi Sacco, Eye Clin, Milan, Italy.
   [Haines, Jonathan L.] Case Western Reserve Univ, Inst Computat Biol, Cleveland, OH 44106 USA.
   [Haines, Jonathan L.] Case Western Reserve Univ, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA.
   [Pericak-Vance, Margaret Ann] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA.
   [Stambolian, Dwight] Univ Penn, Perelman Sch Med, Dept Ophthalmol, Philadelphia, PA 19104 USA.
C3 Doheny Eye Institute; University of California System; University of
   California Los Angeles; University of California System; University of
   California Los Angeles; University of California Los Angeles Medical
   Center; David Geffen School of Medicine at UCLA; University of Milan;
   Luigi Sacco Hospital; Case Western Reserve University; Case Western
   Reserve University; University of Miami; University of Pennsylvania;
   Pennsylvania Medicine
RP Sadda, SR (通讯作者)，UCLA, David Geffen Sch Med, Dept Ophthalmol, Doheny Eye Inst, 1355 San Pablo St, Los Angeles, CA 90033 USA.
EM ssadda@doheny.org
OI Corvi, Federico/0000-0002-2661-5500
CR Balaratnasingam C, 2017, OPHTHALMOLOGY, V124, P644, DOI 10.1016/j.ophtha.2016.12.034
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NR 22
TC 2
Z9 2
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD SEP
PY 2021
VL 41
IS 9
BP 1851
EP 1857
DI 10.1097/IAE.0000000000003158
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA WN5QE
UT WOS:000711821200030
PM 33655896
DA 2022-11-30
ER

PT J
AU George, AK
   Homme, RP
   Stanisic, D
   Tyagi, SC
   Singh, M
AF George, Akash K.
   Homme, Rubens P.
   Stanisic, Dragana
   Tyagi, Suresh C.
   Singh, Mahavir
TI Protecting the aging eye with hydrogen sulfide
SO CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
LA English
DT Review
DE hyperhomocysteinemia; inflammation; redox homeostasis; senescence;
   vision impairment
ID CYSTATHIONINE-BETA-SYNTHASE; CARDIOVASCULAR RISK-FACTORS; TYPE-2
   DIABETES-MELLITUS; OPEN-ANGLE GLAUCOMA; METHYLENETETRAHYDROFOLATE
   REDUCTASE GENE; PLASMA HOMOCYSTEINE LEVELS; MTHFR C677T MUTATION;
   OXIDATIVE STRESS; MACULAR DEGENERATION; VISUAL IMPAIRMENT
AB Research demonstrates that senescence is associated with tissue and organ dysfunction, and the eye is no exception. Sequelae arising from aging have been well defined as distinct clinical entities and vision impairment has significant psychosocial consequences. Retina and adjacent tissues like retinal pigmented epithelium and choroid are the key structures that are required for visual perception. Any structural and functional changes in retinal layers and blood retinal barrier could lead to age-related macular degeneration, diabetic retinopathy, and glaucoma. Further, there are significant oxygen gradients in the eye that can lead to excessive reactive oxygen species, resulting in endoplasmic reticulum and mitochondria' stress response. These radicals are source of functional and morphological impairment in retinal pigmented epithelium and retinal ganglion cells. Therefore, ocular diseases could be summarized as disturbance in the redox homeostasis. Hyperhomocysteinemia is a risk factor and causes vascular occlusive disease of the retina. Interestingly, hydrogen sulfide (H2S) has been proven to be an effective antioxidant agent, and it can help treat diseases by alleviating stress and inflammation. Concurrent glutamate excitotoxicity, endoplasmic reticulum stress, and microglia activation are also linked to stress; thus, H2S may offer additional interventional strategy. A refined understanding of the aging eye along with H2S biology and pharmacology may help guide newer therapies for the eye.
C1 [George, Akash K.; Homme, Rubens P.; Singh, Mahavir] Univ Louisville, Sch Med, Eye & Vis Sci Lab, Dept Physiol, Louisville, KY 40292 USA.
   [Stanisic, Dragana] Univ Kragujevac, Fac Med Sci, Dept Dent, Kragujevac, Serbia.
   [Tyagi, Suresh C.] Univ Louisville, Sch Med, Dept Physiol, Louisville, KY 40292 USA.
C3 University of Louisville; University of Kragujevac; University of
   Louisville
RP Singh, M (通讯作者)，Univ Louisville, Sch Med, Eye & Vis Sci Lab, Dept Physiol, Louisville, KY 40292 USA.
EM mahavir.singh@louisville.edu
OI Stanisic, Dragana/0000-0001-8341-2374
FU National Institutes of Health (USA) [HL139047, AR071789, HL74815,
   HL107640, DK116591]
FX Members in the laboratory (Eye and Vision Science Laboratory, University
   of Louisville School of Medicine) are gratefully acknowledged for their
   continuous support and encouragement. This work was supported by
   HL139047, AR071789, HL74815, HL107640, HL139047, and DK116591 grants
   from the National Institutes of Health (USA).
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NR 171
TC 0
Z9 0
U1 4
U2 10
PU CANADIAN SCIENCE PUBLISHING
PI OTTAWA
PA 65 AURIGA DR, SUITE 203, OTTAWA, ON K2E 7W6, CANADA
SN 0008-4212
EI 1205-7541
J9 CAN J PHYSIOL PHARM
JI Can. J. Physiol. Pharmacol.
PD FEB
PY 2021
VL 99
IS 2
SI SI
BP 161
EP 170
DI 10.1139/cjpp-2020-0216
PG 10
WC Pharmacology & Pharmacy; Physiology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Pharmacology & Pharmacy; Physiology
GA QO3ZR
UT WOS:000623083000005
PM 32721225
DA 2022-11-30
ER

PT J
AU Khan, SM
   Liu, XX
   Nath, S
   Korot, E
   Faes, L
   Wagner, SK
   Keane, PA
   Sebire, NJ
   Burton, MJ
   Denniston, AK
AF Khan, Saad M.
   Liu, Xiaoxuan
   Nath, Siddharth
   Korot, Edward
   Faes, Livia
   Wagner, Siegfried K.
   Keane, Pearse A.
   Sebire, Neil J.
   Burton, Matthew J.
   Denniston, Alastair K.
TI A global review of publicly available datasets for ophthalmological
   imaging: barriers to access, usability, and generalisability
SO LANCET DIGITAL HEALTH
LA English
DT Review
ID DIABETIC-RETINOPATHY; DISEASES; CANCER; SYSTEM
AB Health data that are publicly available are valuable resources for digital health research. Several public datasets containing ophthalmological imaging have been frequently used in machine learning research; however, the total number of datasets containing ophthalmological health information and their respective content is unclear. This Review aimed to identify all publicly available ophthalmological imaging datasets, detail their accessibility, describe which diseases and populations are represented, and report on the completeness of the associated metadata. With the use of MEDLINE, Google's search engine, and Google Dataset Search, we identified 94 open access datasets containing 507 724 images and 125 videos from 122 364 patients. Most datasets originated from Asia, North America, and Europe. Disease populations were unevenly represented, with glaucoma, diabetic retinopathy, and age-related macular degeneration disproportionately overrepresented in comparison with other eye diseases. The reporting of basic demographic characteristics such as age, sex, and ethnicity was poor, even at the aggregate level. This Review provides greater visibility for ophthalmological datasets that are publicly available as powerful resources for research. Our paper also exposes an increasing divide in the representation of different population and disease groups in health data repositories. The improved reporting of metadata would enable researchers to access the most appropriate datasets for their needs and maximise the potential of such resources.
C1 [Khan, Saad M.; Liu, Xiaoxuan; Denniston, Alastair K.] Univ Birmingham, Acad Unit Ophthalmol, Inst Inflammat & Ageing, Coll Med & Dent Sci, Birmingham B15 2TT, W Midlands, England.
   [Liu, Xiaoxuan; Denniston, Alastair K.] Univ Hosp Birmingham NHS Fdn Trust, Dept Ophthalmol, Birmingham, W Midlands, England.
   [Liu, Xiaoxuan; Korot, Edward; Faes, Livia] Moorfields Eye Hosp NHS Fdn Trust, London, England.
   [Liu, Xiaoxuan; Sebire, Neil J.; Denniston, Alastair K.] Hlth Data Res UK, London, England.
   [Liu, Xiaoxuan; Denniston, Alastair K.] Birmingham Hlth Partners, Ctr Regulatory Sci & Innovat, Birmingham, W Midlands, England.
   [Nath, Siddharth] McGill Univ, Dept Ophthalmol & Visual Sci, Montreal, PQ, Canada.
   [Korot, Edward] Stanford Univ, Byers Eye Inst, Palo Alto, CA 94304 USA.
   [Faes, Livia] Cantonal Hosp Lucerne, Eye Clin, Luzern, Switzerland.
   [Wagner, Siegfried K.; Keane, Pearse A.; Denniston, Alastair K.] Moorfields Eye Hosp NHS Fdn Trust, Natl Inst Hlth Res, Biomed Res Ctr Ophthalmol, London, England.
   [Wagner, Siegfried K.; Keane, Pearse A.; Denniston, Alastair K.] UCL Inst Ophthalmol, London, England.
   [Burton, Matthew J.] London Sch Hyg & Trop Med, Int Ctr Eye Hlth, Dept Clin Res, London, England.
C3 University of Birmingham; University of Birmingham; University of
   London; University College London; Moorfields Eye Hospital NHS
   Foundation Trust; McGill University; Stanford University; Lucerne
   Cantonal Hospital; University of London; University College London;
   Moorfields Eye Hospital NHS Foundation Trust; University of London;
   University College London; University of London; London School of
   Hygiene & Tropical Medicine
RP Denniston, AK (通讯作者)，Univ Birmingham, Acad Unit Ophthalmol, Inst Inflammat & Ageing, Coll Med & Dent Sci, Birmingham B15 2TT, W Midlands, England.
EM a.denniston@bham.ac.uk
RI Denniston, Alastair/ABD-1238-2020
OI Denniston, Alastair/0000-0001-7849-0087; Sebire,
   Neil/0000-0001-5348-9063; Burton, Matthew/0000-0003-1872-9169; Liu,
   Xiaoxuan/0000-0002-1286-0038; Keane, Pearse/0000-0002-9239-745X; Korot,
   Edward/0000-0002-5687-1564
FU Queen Elizabeth Diamond Jubilee Trust; Moorfields Eye Charity
   [GR001061]; National Institute for Health Research Moorfields Biomedical
   Research Centre; Wellcome Trust; Sightsavers; Fred Hollows Foundation;
   British Council for the Prevention of Blindness; Christian Blind
   Mission; SEVA Foundation
FX The Lancet Global Health Commission on Global Eye Health is supported by
   The Queen Elizabeth Diamond Jubilee Trust, Moorfields Eye Charity (grant
   no. GR001061), National Institute for Health Research Moorfields
   Biomedical Research Centre, The Wellcome Trust, Sightsavers, The Fred
   Hollows Foundation, The SEVA Foundation, The British Council for the
   Prevention of Blindness, and Christian Blind Mission.
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   2018, GOOGLE AI BLOG
NR 37
TC 46
Z9 46
U1 5
U2 12
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
EI 2589-7500
J9 LANCET DIGIT HEALTH
JI Lancet Digit. Health
PD JAN
PY 2021
VL 3
IS 1
BP E51
EP E66
DI 10.1016/S2589-7500(20)30240-5
PG 16
WC Medical Informatics; Medicine, General & Internal
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Medical Informatics; General & Internal Medicine
GA PN3NE
UT WOS:000604388400011
PM 33735069
OA Green Published, gold
HC Y
HP N
DA 2022-11-30
ER

PT J
AU Droho, S
   Cuda, CM
   Lavine, JA
AF Droho, Steven
   Cuda, Carla M.
   Lavine, Jeremy A.
TI Digestion of Whole Mouse Eyes for Multi-Parameter Flow Cytometric
   Analysis of Mononuclear Phagocytes
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
ID MONOCYTE-DERIVED MACROPHAGES; EXPRESSION; MICROGLIA; ACTIVATION
AB The innate immune system plays important roles in ocular pathophysiology including uveitis, diabetic retinopathy, and age-related macular degeneration. Innate immune cells, specifically mononuclear phagocytes, express overlapping cell surface markers, which makes identifying these populations a challenge. Multi-parameter flow cytometry allows for the simultaneous, quantitative analysis of multiple cell surface markers in order to differentiate monocytes, macrophages, microglia, and dendritic cells in mouse eyes. This protocol describes the enucleation of whole mouse eyes, ocular dissection, digestion into a single cell suspension, and staining of the single cell suspension for myeloid cell markers. Additionally, we explain the proper methods for determining voltages using single color controls and for delineating positive gates using fluorescence minus one controls. The major limitation of multi-parameter flow cytometry is the absence of tissue architecture. This limitation can be overcome by multi-parameter flow cytometry of individual ocular compartments or complimentary immunofluorescence staining. However, immunofluorescence is limited by its lack of quantitative analysis and reduced number of fluorophores on most microscopes. We describe the use of multi-parametric flow cytometry to provide highly quantitative analysis of mononuclear phagocytes in laser-induced choroidal neovascularization. Additionally, multi-parameter flow cytometry can be used for the identification of macrophage subsets, fate mapping, and cell sorting for transcriptomic or proteomic studies.
C1 [Droho, Steven; Lavine, Jeremy A.] Northwestern Univ, Feinberg Sch Med, Dept Ophthalmol, Evanston, IL 60208 USA.
   [Cuda, Carla M.] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Rheumatol, Evanston, IL 60208 USA.
C3 Northwestern University; Feinberg School of Medicine; Northwestern
   University; Feinberg School of Medicine
RP Lavine, JA (通讯作者)，Northwestern Univ, Feinberg Sch Med, Dept Ophthalmol, Evanston, IL 60208 USA.
EM jeremy.lavine@northwestern.edu
OI Lavine, Jeremy/0000-0002-0884-1336
FU NIH [K08EY030923]; K01 grant from the NIH National Institute of
   Arthritis and Musculoskeletal Diseases [5K01AR060169]; Novel Research
   Grant from the Lupus Research Alliance [637405]
FX JAL was supported by NIH grant K08EY030923; CMC was supported by a K01
   grant (5K01AR060169) from the NIH National Institute of Arthritis and
   Musculoskeletal Diseases and a Novel Research Grant (637405) from the
   Lupus Research Alliance.
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NR 28
TC 4
Z9 4
U1 1
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 JUN
PY 2020
IS 160
AR e61348
DI 10.3791/61348
PG 20
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA MH1NJ
UT WOS:000546499200095
PM 32628177
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Maccarone, R
   Tisi, A
   Passacantando, M
   Ciancaglini, M
AF Maccarone, Rita
   Tisi, Annamaria
   Passacantando, Maurizio
   Ciancaglini, Marco
TI Ophthalmic Applications of Cerium Oxide Nanoparticles
SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
DE nanoceria; retina; lens; nanotechnology; nanomedicine; eye
ID OXIDATIVE STRESS; INTRAVITREAL INJECTION; MACULAR DEGENERATION; TUBBY
   MICE; NANOCERIA; ANTIOXIDANT; EXPOSURE; INFLAMMATION; INHIBITION;
   MECHANISMS
AB Cerium oxide nanoparticles (CeO2-NPs; or nanoceria) have been largely studied for biomedical applications due to their peculiar auto-regenerative antioxidant activity. This review focuses on ophthalmic applications of nanoceria. Many in vivo data indicate that nanoceria protect the retina from neurodegeneration. In particular, they have been tested in animal models of age-related macular degeneration and retinitis pigmentosa and their neuroprotective properties have been shown to persist for a long time, without any collateral effects. In vitro cytotoxicity studies have shown that CeO2-NPs could be safe for lens cells and could represent a new therapy for cataract treatment, but further studies are needed. To date, different pharmaceutical formulations based on nanoceria have been created looking at future clinical ophthalmic applications, such as water-soluble nanoceria, glycol chitosan-coated ceria nanoparticles (GCCNPs), and alginate-gelatin hydrogel loaded GCCNPs. GCCNPs were also effective in preventing choroidal neovascularization in vivo. Based on the nanosize of nanoceria, corneal permeation could be achieved to allow topical treatment of nanoceria. PEGylation and encapsulation in liposomes represent the main strategies to support corneal permeation, without altering nanoceria chemical-physical properties. Based on their great antioxidant properties, safety, and nanosize, nanoceria represent a new potential therapeutic for the treatment of several eye disorders.
C1 [Maccarone, Rita; Tisi, Annamaria] Univ Aquila, Dept Biotechnol & Appl Clin Sci, Via Vetoio,Coppito 2, I-67100 Laquila, Italy.
   [Passacantando, Maurizio] Univ Aquila, Dept Phys & Chem Sci, Laquila, Italy.
   [Ciancaglini, Marco] Univ Aquila, Dept Life Hlth & Environm Sci, Laquila, Italy.
C3 University of L'Aquila; University of L'Aquila; University of L'Aquila
RP Maccarone, R (通讯作者)，Univ Aquila, Dept Biotechnol & Appl Clin Sci, Via Vetoio,Coppito 2, I-67100 Laquila, Italy.
EM rita.maccarone@univaq.it
OI MACCARONE, Rita/0000-0003-0648-3771; Ciancaglini,
   Marco/0000-0001-5888-7976
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NR 59
TC 20
Z9 20
U1 5
U2 28
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 JUL 1
PY 2020
VL 36
IS 6
BP 376
EP 383
DI 10.1089/jop.2019.0105
EA DEC 2019
PG 8
WC Ophthalmology; Pharmacology & Pharmacy
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology; Pharmacology & Pharmacy
GA MQ6GC
UT WOS:000505016700001
PM 31891528
DA 2022-11-30
ER

PT J
AU Regent, F
   Morizur, L
   Lesueur, L
   Habeler, W
   Plancheron, A
   Ben M'Barek, K
   Monville, C
AF Regent, Florian
   Morizur, Lise
   Lesueur, Lea
   Habeler, Walter
   Plancheron, Alexandra
   Ben M'Barek, Karim
   Monville, Christelle
TI Automation of human pluripotent stem cell differentiation toward retinal
   pigment epithelial cells for large-scale productions
SO SCIENTIFIC REPORTS
LA English
DT Article
ID DIRECTED DIFFERENTIATION; MACULAR DEGENERATION; DERIVATION; RPE;
   MAINTENANCE; THERAPIES; EXPANSION; CULTURE; MODELS
AB Dysfunction or death of retinal pigment epithelial (RPE) cells is involved in some forms of Retinitis Pigmentosa and in age-related macular degeneration (AMD). Since there is no cure for most patients affected by these diseases, the transplantation of RPE cells derived from human pluripotent stem cells (hPSCs) represents an attractive therapeutic alternative. First attempts to transplant hPSC-RPE cells in AMD and Stargardt patients demonstrated the safety and suggested the potential efficacy of this strategy. However, it also highlighted the need to upscale the production of the cells to be grafted in order to treat the millions of potential patients. Automated cell culture systems are necessary to change the scale of cell production. In the present study, we developed a protocol amenable for automation that combines in a sequential manner Nicotinamide, Activin A and CHIR99021 to direct the differentiation of hPSCs into RPE cells. This novel differentiation protocol associated with the use of cell culture robots open new possibilities for the production of large batches of hPSC-RPE cells while maintaining a high cell purity and functionality. Such methodology of cell culture automation could therefore be applied to various differentiation processes in order to generate the material suitable for cell therapy.
C1 [Regent, Florian; Morizur, Lise; Lesueur, Lea; Habeler, Walter; Plancheron, Alexandra; Ben M'Barek, Karim; Monville, Christelle] Inst Stem Cell Therapy & Explorat Monogen Dis, INSERM U861, I Stem, AFM, F-91100 Corbeil Essonnes, France.
   [Regent, Florian; Morizur, Lise; Lesueur, Lea; Habeler, Walter; Plancheron, Alexandra; Ben M'Barek, Karim; Monville, Christelle] Inst Stem Cell Therapy & Explorat Monogen Dis, UEVE U861, I Stem, AFM, F-91100 Corbeil Essonnes, France.
   [Morizur, Lise; Lesueur, Lea; Habeler, Walter; Plancheron, Alexandra; Ben M'Barek, Karim] Inst Stem Cell Therapy & Explorat Monogen Dis, CECS, I Stem, AFM, F-91100 Corbeil Essonnes, France.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm);
   UDICE-French Research Universities; Universite Paris Saclay;
   UDICE-French Research Universities; Universite Paris Saclay;
   UDICE-French Research Universities; Universite Paris Saclay
RP Monville, C (通讯作者)，Inst Stem Cell Therapy & Explorat Monogen Dis, INSERM U861, I Stem, AFM, F-91100 Corbeil Essonnes, France.; Monville, C (通讯作者)，Inst Stem Cell Therapy & Explorat Monogen Dis, UEVE U861, I Stem, AFM, F-91100 Corbeil Essonnes, France.
EM cmonville@istem.fr
RI M'BAREK, Karim BEN/K-1389-2019
OI M'BAREK, Karim BEN/0000-0002-2556-0325; Morizur,
   Lise/0000-0001-7400-3018; Monville, Christelle/0000-0003-1256-5140
FU LABEX REVIVE [ANR-10-LABX-73]; NeurATRIS, a translational research
   infrastructure (Investissements d'Avenir) for biotherapies in
   Neurosciences [ANR-11-INBS-0011]; Association Francaise contre les
   Myopathies (AFM)-Telethon; INGESTEM, the national infrastructure
   (Investissements d'Avenir) engineering for pluripotent and
   differentiated stem cells [ANR-11-INBS-000]
FX We thank E. Nandrot for the gift of FITC-labeled photoreceptor cell
   outer segment preparations from pigs. We thank Roslin Cells for
   providing RC-09 hESCs. This work was supported by grants from LABEX
   REVIVE [ANR-10-LABX-73]. It was supported by NeurATRIS, a translational
   research infrastructure (Investissements d'Avenir) for biotherapies in
   Neurosciences [ANR-11-INBS-0011] and INGESTEM, the national
   infrastructure (Investissements d'Avenir) engineering for pluripotent
   and differentiated stem cells [ANR-11-INBS-000]. I-Stem is part of the
   Biotherapies Institute for Rare Diseases supported by the Association
   Francaise contre les Myopathies (AFM)-Telethon.
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NR 47
TC 26
Z9 26
U1 1
U2 5
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 2019
VL 9
AR 10646
DI 10.1038/s41598-019-47123-6
PG 11
WC Multidisciplinary Sciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Science & Technology - Other Topics
GA IK6SP
UT WOS:000476718900033
PM 31337830
OA Green Published, gold
DA 2022-11-30
ER

PT J
AU Chua, CEL
   Tang, BL
AF Chua, Christelle En Lin
   Tang, Bor Luen
TI miR-34a in Neurophysiology and Neuropathology
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Review
DE miR-34a; Alzheimer's disease; Tp53; SIRT1; SIRT6; Neuropathology
ID NF-KAPPA-B; HAIR CELL APOPTOSIS; MICRORNA EXPRESSION; DOWN-REGULATION;
   ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; GENE-EXPRESSION; SYNAPTIC
   PLASTICITY; CEREBROSPINAL-FLUID; COGNITIVE FUNCTION
AB Epigenetic influence of brain and neuronal function plays key regulatory roles in health and diseases. The microRNA miR-34a is a tumor suppressor transcript, and its loss has been prominently linked to various human cancers, including malignancies of the brain. Interestingly, miR-34a is abundantly expressed in the adult mammalian brain, and emerging evidence has implicated its involvement in a range of neurodevelopmental and neuropathological processes. Developmentally, miR-34a regulates neural stem/progenitor cell differentiation and aspects of neurogenesis. During aging, its elevation is connected to hearing loss and age-related macular degeneration. Pathologically, its elevations during epileptic seizures and ischemic stroke contribute to neuronal injury and death. Inhibition or suppression of miR-34a improved neuronal survival against a variety of neurotoxins implicated in Parkinson's disease. Its elevation may also play a role in neuronal demise in animal models of Alzheimer's disease, and suppression of its levels may be generally neuroprotective. The roles and activities of miR-34a in the brain are modulated by factors that control its expression (such as Tp53/73), as well as its downstream target genes (such as the sirtuins SIRT1 and SIRT6) and signaling pathways (such the Notch pathway). We discuss here the known and emerging roles of the miR-34a regulatory network in neurophysiology and neuropathology.
C1 [Chua, Christelle En Lin] Natl Univ Singapore, Singapore Nucl Res & Safety Initiat, Singapore, Singapore.
   [Tang, Bor Luen] Natl Univ Hlth Syst, Dept Biochem, Yong Loo Lin Sch Med, Singapore, Singapore.
   [Tang, Bor Luen] Natl Univ Singapore, NUS Grad Sch Integrat Sci & Engn, Singapore, Singapore.
C3 National University of Singapore; National University of Singapore;
   National University of Singapore
RP Tang, BL (通讯作者)，Natl Univ Hlth Syst, Dept Biochem, Yong Loo Lin Sch Med, Singapore, Singapore.; Tang, BL (通讯作者)，Natl Univ Singapore, NUS Grad Sch Integrat Sci & Engn, Singapore, Singapore.
EM bchtbl@nus.edu.sg
RI Tang, Bor Luen/E-4548-2012
OI Tang, Bor Luen/0000-0002-1925-636X
FU NUS Graduate School for Integrative Sciences and Engineering
FX BLT is supported by the NUS Graduate School for Integrative Sciences and
   Engineering
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NR 145
TC 27
Z9 29
U1 0
U2 18
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
EI 1559-1166
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD FEB
PY 2019
VL 67
IS 2
BP 235
EP 246
DI 10.1007/s12031-018-1231-y
PG 12
WC Biochemistry & Molecular Biology; Neurosciences
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA HK7CO
UT WOS:000458145400007
PM 30488149
DA 2022-11-30
ER

PT J
AU Recalde, S
   Tortajada, A
   Subias, M
   Anter, J
   Blasco, M
   Maranta, R
   Coco, R
   Pinto, S
   Noris, M
   Garcia-Layana, A
   de Cordoba, SR
AF Recalde, Sergio
   Tortajada, Agustin
   Subias, Marta
   Anter, Jaouad
   Blasco, Miguel
   Maranta, Ramona
   Coco, Rosa
   Pinto, Sheila
   Noris, Marina
   Garcia-Layana, Alfredo
   Rodriguez de Cordoba, Santiago
TI Molecular Basis of Factor H R1210C Association with Ocular and Renal
   Diseases
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID COMPLEMENT FACTOR-H; HEMOLYTIC-UREMIC SYNDROME; DENSE DEPOSIT DISEASE;
   MACULAR DEGENERATION; MUTATIONS; RISK; VARIANT; GLOMERULONEPHRITIS;
   POLYMORPHISM; REVEALS
AB The complement factor H (FH) mutation R1210C, which was described in association with atypical hemolytic uremic syndrome (aHUS), also confers high risk of age related macular degeneration (AMD) and associates with C3 glomerulopathy (C3G). To reveal the molecular basis of these associations and to provide insight into what determines the disease phenotype in FH-R1210C carriers, we identified FH-R1210C carriers in our aHUS, C3G, and AMD cohorts. Disease status, determined in patients and relatives, revealed an absence of AMD phenotypes in the aHUS cohort and, vice versa, a lack of renal disease in the AMD cohort. These findings were consistent with differences in the R1210C-independent overall risk for aHUS and AMD between mutation carriers developing one pathology or the other. R1210C is an unusual mutation that generates covalent complexes between FH and HSA. Using purified FH proteins and surface plasmon resonance analyses, we demonstrated that formation of these FH-HSA complexes impairs accessibility to all FH functional domains. These data suggest that R1210C is a unique C-terminal FH mutation that behaves as a partial FH deficiency, predisposing individuals to diverse pathologies with distinct underlying pathogenic mechanisms; the final disease outcome is then determined by R1210C-independent genetic risk factors.
C1 [Recalde, Sergio; Garcia-Layana, Alfredo] Univ Navarra Clin, Dept Ophthalmol, Navarra, Spain.
   [Tortajada, Agustin; Subias, Marta; Anter, Jaouad; Pinto, Sheila; Rodriguez de Cordoba, Santiago] Biol Res Ctr, Dept Cellular & Mol Med, Ramiro Maeztu 9, Madrid 28040, Spain.
   [Tortajada, Agustin; Subias, Marta; Anter, Jaouad; Pinto, Sheila; Rodriguez de Cordoba, Santiago] Ctr Biomed Network Res Rare Dis, Ramiro Maeztu 9, Madrid 28040, Spain.
   [Blasco, Miguel] Univ Barcelona, Hosp Clin, Nephrol & Kidney Transplant Unit, Barcelona, Spain.
   [Maranta, Ramona; Noris, Marina] Aldo & Cele Dacco Clin Res Ctr Rare Dis, Mario Negri Inst Pharmacol Res, Bergamo, Italy.
   [Coco, Rosa] Univ Valladolid, Inst Appl Ophthalmol, Valladolid, Spain.
C3 University of Navarra; Consejo Superior de Investigaciones Cientificas
   (CSIC); CSIC - Centro de Investigaciones Biologicas (CIB); CIBER -
   Centro de Investigacion Biomedica en Red; CIBERER; University of
   Barcelona; Hospital Clinic de Barcelona; Istituto di Ricerche
   Farmacologiche Mario Negri IRCCS; Universidad de Valladolid
RP de Cordoba, SR (通讯作者)，Biol Res Ctr, Dept Cellular & Mol Med, Ramiro Maeztu 9, Madrid 28040, Spain.; de Cordoba, SR (通讯作者)，Ctr Biomed Network Res Rare Dis, Ramiro Maeztu 9, Madrid 28040, Spain.
EM srdecordoba@cib.csic.es
RI Recalde, Sergio/D-1815-2017; Martin, Rosa Maria Coco/H-4511-2015;
   Tortajada, Agustín/H-2857-2015; NORIS, MARINA/ABG-2219-2020; Rodriguez
   de Cordoba, Santiago/K-6727-2014
OI Recalde, Sergio/0000-0002-9328-9725; Martin, Rosa Maria
   Coco/0000-0002-1811-1417; Tortajada, Agustín/0000-0002-2131-2594; NORIS,
   MARINA/0000-0001-7651-5033; Rodriguez de Cordoba,
   Santiago/0000-0001-6401-1874
FU Spanish Ministry of Economy and Competitiveness [SAF2011-26583,
   PI11/00898, RETICS RD12/0034]; Inigo Alvarez de Toledo Renal Foundation;
   European Union [305608]; Autonomous Region of Madrid [S2010/BMD-2316];
   Aid Foundation for Research on Rare Diseases
FX This work was supported by grants from the Spanish Ministry of Economy
   and Competitiveness (SAF2011-26583, PI11/00898, and RETICS RD12/0034),
   the Inigo Alvarez de Toledo Renal Foundation, the European Union Seventh
   Framework Programme EURenOmics Project (305608), and the Autonomous
   Region of Madrid (S2010/BMD-2316). R.M. is recipient of a fellowship
   from the Aid Foundation for Research on Rare Diseases.
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NR 32
TC 23
Z9 24
U1 0
U2 9
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD MAY
PY 2016
VL 27
IS 5
BP 1305
EP 1311
DI 10.1681/ASN.2015050580
PG 7
WC Urology & Nephrology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Urology & Nephrology
GA DK9FR
UT WOS:000375236700010
PM 26376859
OA Bronze, Green Published, Green Submitted
DA 2022-11-30
ER

PT J
AU He, LM
   Silva, RA
   Moshfeghi, DM
   Blumenkranz, MS
   Leng, T
AF He, Lingmin
   Silva, Ruwan A.
   Moshfeghi, Darius M.
   Blumenkranz, Mark S.
   Leng, Theodore
TI AFLIBERCEPT FOR THE TREATMENT OF RETINAL PIGMENT EPITHELIAL DETACHMENTS
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE anti-vascular endothelial growth factor antibody; neovascular
   age-related macular degeneration; pigment epithelial detachment;
   aflibercept; ranibizumab; bevacizumab
ID MACULAR DEGENERATION; INTRAVITREAL AFLIBERCEPT; ANATOMICAL OUTCOMES;
   RANIBIZUMAB; BEVACIZUMAB; EYES; THERAPY; TRIAL; FLUID
AB Purpose:To compare anatomical and visual acuity outcomes of eyes with persistent pigment epithelial detachments (PEDs) secondary to exudative age-related macular degeneration despite ranibizumab or bevacizumab treatment.Methods:After institutional review board approval, 40 eyes with PEDs switched from ranibizumab or bevacizumab to intravitreal aflibercept were compared for logMAR visual acuity, central subfield thickness on spectral domain optical coherence tomography, and PED height. Using paired t-tests, these parameters at baseline, after 3 consecutive injections, and 1 year after the switch were compared.Results:Baseline visions of 20/61 3.99 lines declined after 3 injections with aflibercept by 0.39 +/- 2.43 lines (P = 0.32) and continued to fall after 1 year by 1.27 +/- 3.48 lines (P = 0.03). Central subfield thickness was reduced after 3 injections (9.1 +/- 52.0 m, P = 0.27) and after 1 year (24.4 +/- 55.3 m, P = 0.01). The height of PEDs decreased by 31.7 +/- 71.53 m (P = 0.008) after 3 injections and by 47.81 +/- 77.94 m (P < 0.001) after 1 year.Conclusion:Switching to aflibercept from ranibizumab or bevacizumab resulted in a reduction in the height of PED and central subfield thickness, but a trend toward worse visual acuity 1 year after the switch.
C1 [He, Lingmin; Silva, Ruwan A.; Moshfeghi, Darius M.; Blumenkranz, Mark S.; Leng, Theodore] Stanford Univ, Sch Med, Byers Eye Inst, Palo Alto, CA 94304 USA.
C3 Stanford University
RP Leng, T (通讯作者)，Stanford Univ, Dept Ophthalmol, Byers Eye Inst, 2452 Watson Court, Palo Alto, CA 94303 USA.
EM tedleng@stanford.edu
RI Leng, Theodore/AAQ-7459-2020
OI Moshfeghi, Darius Mohammad/0000-0003-2254-292X; Leng,
   Theodore/0000-0002-8461-3562
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NR 34
TC 19
Z9 19
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 MAR
PY 2016
VL 36
IS 3
BP 492
EP 498
DI 10.1097/IAE.0000000000000749
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA DG1MW
UT WOS:000371833200008
PM 26398694
DA 2022-11-30
ER

PT J
AU Lin, JB
   Mast, N
   Bederman, IR
   Li, Y
   Brunengraber, H
   Bjorkhem, I
   Pikuleva, IA
AF Lin, Joseph B.
   Mast, Natalia
   Bederman, Ilya R.
   Li, Yong
   Brunengraber, Henri
   Bjorkhem, Ingemar
   Pikuleva, Irina A.
TI Cholesterol in mouse retina originates primarily from in situ de novo
   biosynthesis
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE dietary cholesterol; lipoproteins; low density lipoprotein; mass
   spectrometry; brain lipids; cholesterol uptake; deuterium; age-related
   macular degeneration; isotopic tracer
ID MASS ISOTOPOMER ANALYSIS; MACULAR DEGENERATION; DEUTERATED WATER;
   VERTEBRATE RETINA; LIPID-METABOLISM; APOLIPOPROTEIN-E; VIVO MEASUREMENT;
   BRAIN; MICE; ASSOCIATION
AB The retina, a thin tissue in the back of the eye, has two apparent sources of cholesterol: in situ biosynthesis and cholesterol available from the systemic circulation. The quantitative contributions of these two cholesterol sources to the retinal cholesterol pool are unknown and have been determined in the present work. A new methodology was used. Mice were given separately deuterium-labeled drinking water and chow containing 0.3% deuterium-labeled cholesterol. In the retina, the rate of total cholesterol input was 21 mu g of cholesterol/g retina . day, of which 15 mu g of cholesterol/g retina . day was provided by local biosynthesis and 6 mu g of cholesterol/g retina . day was uptaken from the systemic circulation. Thus, local cholesterol biosynthesis accounts for the majority (72%) of retinal cholesterol input. We also quantified cholesterol input to mouse brain, the organ sharing important similarities with the retina. The rate of total cerebral cholesterol input was 121 mu g of cholesterol/g brain . day with local biosynthesis providing 97% of total cholesterol input. Our work addresses a long-standing question in eye research and adds new knowledge to the potential use of statins (drugs that inhibit cholesterol biosynthesis) as therapeutics for age-related macular degeneration, a common blinding disease.
C1 [Lin, Joseph B.; Mast, Natalia; Li, Yong; Pikuleva, Irina A.] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
   [Bederman, Ilya R.] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA.
   [Brunengraber, Henri] Case Western Reserve Univ, Dept Nutr, Cleveland, OH 44106 USA.
   [Bjorkhem, Ingemar] Karolinska Univ Hosp, Karolinska Inst, Div Clin Chem, Dept Lab Med, S-14186 Stockholm, Sweden.
C3 Case Western Reserve University; Case Western Reserve University; Case
   Western Reserve University; Karolinska Institutet; Karolinska University
   Hospital
RP Pikuleva, IA (通讯作者)，Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
EM iap8@case.edu
OI Pikuleva, Irina/0000-0001-9742-6232; Bjorkhem,
   Ingemar/0000-0002-0575-9425; Lin, Joseph/0000-0001-6667-9018
FU National Institutes of Health [R01 EY018383]; American Society for
   Pharmacology and Experimental Therapeutics; Research to Prevent
   Blindness [EY11373]; Swedish Research Council; Swedish Brain Power;
   NATIONAL EYE INSTITUTE [P30EY011373, R01EY018383] Funding Source: NIH
   RePORTER
FX This work was supported in part by National Institutes of Health Grant
   R01 EY018383 (I.A.P.), a Fellowship for Summer Undergraduate Research
   from the American Society for Pharmacology and Experimental Therapeutics
   (J.B.L.), an unrestricted grant from Research to Prevent Blindness, Core
   Facility P30 Grant EY11373, and grants from the Swedish Research Council
   and Swedish Brain Power (I.B.). I.A.P. is a Carl F. Asseff Professor of
   Ophthalmology. The contents are solely the responsibility of the authors
   and do not necessarily represent the official views of the National
   Institutes of Health.
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NR 45
TC 28
Z9 28
U1 1
U2 7
PU ELSEVIER
PI AMSTERDAM
PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
SN 0022-2275
EI 1539-7262
J9 J LIPID RES
JI J. Lipid Res.
PD FEB
PY 2016
VL 57
IS 2
BP 258
EP 264
DI 10.1194/jlr.M064469
PG 7
WC Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA DC3AN
UT WOS:000369091600009
PM 26630912
OA hybrid, Green Published
DA 2022-11-30
ER

PT J
AU Dong, LJ
   Nian, H
   Shao, Y
   Zhang, Y
   Li, QT
   Yi, Y
   Tian, F
   Li, WB
   Zhang, H
   Zhang, XM
   Wang, F
   Li, XR
AF Dong, Lijie
   Nian, Hong
   Shao, Yan
   Zhang, Yan
   Li, Qiutang
   Yi, Yue
   Tian, Fang
   Li, Wenbo
   Zhang, Hong
   Zhang, Xiaomin
   Wang, Fei
   Li, Xiaorong
TI PTB-associated splicing factor inhibits IGF-1-induced VEGF upregulation
   in a mouse model of oxygen-induced retinopathy
SO CELL AND TISSUE RESEARCH
LA English
DT Article
DE Polypyrimidine tract-binding protein-associated splicing factor (PSF);
   Insulin-like growth factor-1 (IGF-1); Vascular endothelial growth factor
   (VEGF); Hakai; Retinal neovascularization (RNV)
ID ENDOTHELIAL GROWTH-FACTOR; RESPONSE ELEMENT; TRANSCRIPTIONAL ACTIVITY;
   FACTOR-I; RETINAL NEOVASCULARIZATION; DIABETIC-RETINOPATHY;
   CELL-PROLIFERATION; NEGATIVE REGULATOR; FACTOR EXPRESSION; C-CBL
AB Pathological retinal neovascularization, including retinopathy of prematurity and age-related macular degeneration, is the most common cause of blindness worldwide. Insulin-like growth factor-1 (IGF-1) has a direct mitogenic effect on endothelial cells, which is the basis of angiogenesis. Vascular endothelial growth factor (VEGF) activation in response to IGF-1 is well documented; however, the molecular mechanisms responsible for the termination of IGF-1 signaling are still not completely elucidated. Here, we show that the polypyrimidine tract-binding protein-associated splicing factor (PSF) is a potential negative regulator of VEGF expression induced by IGF stimulation. Functional analysis demonstrated that ectopic expression of PSF inhibits IGF-1-stimulated transcriptional activation and mRNA expression of the VEGF gene, whereas knockdown of PSF increased IGF-1stimulated responses. PSF recruited Hakai to the VEGF transcription complex, resulting in inhibition of IGF-1-mediated transcription. Transfection with Hakai siRNA reversed the PSF-mediated transcriptional repression of VEGF gene transcription. In summary, these results show that PSF can repress the transcriptional activation of VEGF stimulated by IGF-1 via recruitment of the Hakai complex and delineate a novel regulatory mechanism of IGF-1/VEGF signaling that may have implications in the pathogenesis of neovascularization in ocular diseases.
C1 [Dong, Lijie; Nian, Hong; Shao, Yan; Zhang, Yan; Yi, Yue; Tian, Fang; Li, Wenbo; Zhang, Hong; Zhang, Xiaomin; Wang, Fei; Li, Xiaorong] Tianjin Med Univ, Hosp Eye, Tianjin, Peoples R China.
   [Dong, Lijie; Nian, Hong; Zhang, Yan; Yi, Yue; Zhang, Xiaomin; Wang, Fei; Li, Xiaorong] Tianjin Med Univ, Inst Eye, Tianjin, Peoples R China.
   [Dong, Lijie; Nian, Hong; Shao, Yan; Zhang, Yan; Yi, Yue; Tian, Fang; Li, Wenbo; Zhang, Hong; Zhang, Xiaomin; Wang, Fei; Li, Xiaorong] TMU, Sch Optometry & Ophthalmol, Tianjin 300384, Peoples R China.
   [Wang, Fei] Jiangsu Berkgen Biopharmaceut Inc Ltd, Yangzhou 225128, Jiangsu, Peoples R China.
   [Li, Qiutang] Univ Louisville, Sch Med, Dept Ophthalmol & Visual Sci, Louisville, KY 40292 USA.
C3 Tianjin Medical University; Tianjin Medical University; University of
   Louisville
RP Dong, LJ (通讯作者)，TMU, Sch Optometry & Ophthalmol, 251 Fu Kang Rd, Tianjin 300384, Peoples R China.
EM aitaomubang@126.com; wangfei@berkgen.com; xiaorli@163.com
RI li, wenbo/GZM-8930-2022
OI Zhang, Xiaomin/0000-0003-4898-4152
FU National Natural Science Foundation of China [NSFC: 31100991, 81400425];
   Tianjin Municipal Science and Technology Commission [13JCYBJC23300,
   11JCYBJC09900]; Ministry of Education [20111202110009]; Tianjin Medical
   University Eye Hospital Science Grant of PhD [20120403]
FX This work was supported by a grant from the National Natural Science
   Foundation of China (NSFC: 31100991, 81400425), Tianjin Municipal
   Science and Technology Commission Grants (13JCYBJC23300,11JCYBJC09900),
   the joint project by Doctoral Fund of Ministry of Education doctoral
   subject (20111202110009), and Tianjin Medical University Eye Hospital
   Science Grant of PhD (20120403).
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NR 39
TC 17
Z9 30
U1 1
U2 17
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0302-766X
EI 1432-0878
J9 CELL TISSUE RES
JI Cell Tissue Res.
PD MAY
PY 2015
VL 360
IS 2
BP 233
EP 243
DI 10.1007/s00441-014-2104-5
PG 11
WC Cell Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Cell Biology
GA CJ5XS
UT WOS:000355567700004
PM 25638408
DA 2022-11-30
ER

PT J
AU Zhang, PB
   Dufresne, C
   Turner, R
   Ferri, S
   Venkatraman, V
   Karani, R
   Lutty, GA
   Van Eyk, JE
   Semba, RD
AF Zhang, Pingbo
   Dufresne, Craig
   Turner, Randi
   Ferri, Sara
   Venkatraman, Vidya
   Karani, Rabia
   Lutty, Gerard A.
   Van Eyk, Jennifer E.
   Semba, Richard D.
TI The proteome of human retina
SO PROTEOMICS
LA English
DT Article
DE Age-related macular degeneration; Biomedicine; Eye; Human;
   Phototransduction; Retina
ID MACULAR DEGENERATION; STATISTICAL-MODEL; MECHANISMS; IDENTIFICATIONS;
   DATABASE
AB The retina is a delicate tissue that detects light, converts photochemical energy into neural signals, and transmits the signals to the visual cortex of the brain. A detailed protein inventory of the proteome of the normal human eye may provide a foundation for new investigations into both the physiology of the retina and the pathophysiology of retinal diseases. To provide an inventory, proteins were extracted from five retinas of normal eyes and fractionated using SDS-PAGE. After in-gel digestion, peptides were analyzed in duplicate using LC-MS/MS on an Orbitrap Elite mass spectrometer. A total of 3436 nonredundant proteins were identified in the human retina, including 20 unambiguous protein isoforms, of which eight have not previously been demonstrated to exist at the protein level. The proteins identified in the retina included most of the enzymes involved in the visual cycle and retinoid metabolism. One hundred and fifty-eight proteins that have been associated with age-related macular degeneration were identified in the retina. The MS proteome database of the human retina may serve as a valuable resource for future investigations of retinal biology and disease. All MS data have been deposited in the ProteomeXchange with identifier PXD001242 (http://proteomecentral.proteomexchange.org/dataset/PXD001242).
C1 [Zhang, Pingbo; Turner, Randi; Ferri, Sara; Karani, Rabia; Lutty, Gerard A.; Semba, Richard D.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
   [Dufresne, Craig] Thermo Fisher Sci, W Palm Beach, FL USA.
   [Ferri, Sara] Rochester Eye Associates, Rochester, NY USA.
   [Venkatraman, Vidya; Van Eyk, Jennifer E.] Cedars Sinai Med Ctr, Adv Clin BioSyst Res Inst, Inst Heart, Los Angeles, CA 90048 USA.
   [Venkatraman, Vidya; Van Eyk, Jennifer E.] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA.
C3 Johns Hopkins University; Thermo Fisher Scientific; Cedars Sinai Medical
   Center; Cedars Sinai Medical Center
RP Semba, RD (通讯作者)，Wilmer Eye Inst, Smith Bldg,M015,400 N Broadway, Baltimore, MD 21287 USA.
EM rdsemba@jhmi.edu
FU National Institutes of Health [R01 EY024596, R01 AG027012]; Research to
   Prevent Blindness; NATIONAL EYE INSTITUTE [R01EY024596] Funding Source:
   NIH RePORTER; NATIONAL INSTITUTE ON AGING [R01AG027012] Funding Source:
   NIH RePORTER
FX The MS proteomics data in this paper have been deposited in the
   ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org)
   via the PRIDE partner repository [14]: dataset identifier PXD001242.
   This work was supported by the National Institutes of Health grants R01
   EY024596, R01 AG027012, and Research to Prevent Blindness.
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NR 14
TC 26
Z9 26
U1 0
U2 10
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1615-9853
EI 1615-9861
J9 PROTEOMICS
JI Proteomics
PD FEB
PY 2015
VL 15
IS 4
SI SI
BP 836
EP 840
DI 10.1002/pmic.201400397
PG 5
WC Biochemical Research Methods; Biochemistry & Molecular Biology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology
GA CC0CM
UT WOS:000350002600021
PM 25407473
OA Green Accepted
DA 2022-11-30
ER

PT J
AU Vogel, CW
   Finnegan, PW
   Fritzinger, DC
AF Vogel, Carl-Wilhelm
   Finnegan, Paul W.
   Fritzinger, David C.
TI Humanized cobra venom factor: Structure, activity, and therapeutic
   efficacy in preclinical disease models
SO MOLECULAR IMMUNOLOGY
LA English
DT Review
DE Cobra venom factor (CVF); Humanized cobra venom factor; Complement
   depletion; Complement therapeutics
ID ALTERNATIVE COMPLEMENT PATHWAY; FACTOR HYBRID PROTEINS; HUMAN C3
   DERIVATIVES; MANNOSE-BINDING LECTIN; FACTOR-VIII; 3RD COMPONENT;
   FACTOR-B; MYASTHENIA-GRAVIS; FACTOR CVF; IN-VIVO
AB The complement system is an integral component of both innate and adaptive immunity. However, complement is also a pathogenetic factor in many diseases. The development of agents for therapeutic complement inhibition is the topic of intense investigations by many investigators. We have developed a distinctly different therapeutic approach: complement depletion rather than inhibition. This approach is based on cobra venom factor (CVF), a C3 analog known to be able to safely deplete complement. This manuscript will briefly review the structure and activity of CVF, along with its similarities and differences to C3. Exploiting the knowledge of the structure/function relationship of CVF and C3, we created derivatives of human C3 which display the CVF-like activity of depleting complement, referred to as humanized CVF (hCVF). This review describes the structure and activity of hCVF, including the important property of not cleaving C5. The efficacy of hCVF for therapeutic complement depletion in nine preclinical models diseases with complement pathology is reviewed, including reperfusion injury, age-related macular degeneration (AMD), paroxysmal nocturnal hemoglobinuria (PNH), and immunogenicity of Factor VIII in hemophilia A. Complement depletion is characterized by the absence of toxicity, even after intra-arterial injection into the pulmonary artery of primates. No immunogenicity has been observed. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Vogel, Carl-Wilhelm; Fritzinger, David C.] Univ Hawaii, Ctr Canc, Honolulu, HI 96813 USA.
   [Vogel, Carl-Wilhelm] Univ Hawaii, John A Burns Sch Med, Dept Pathol, Honolulu, HI 96813 USA.
   [Finnegan, Paul W.] Del Mar Bioconsulting, Del Mar, CA 92014 USA.
C3 Cancer Research Center of Hawaii; University of Hawaii System;
   University of Hawaii System
RP Vogel, CW (通讯作者)，Univ Hawaii, Ctr Canc, 701 Ilalo St, Honolulu, HI 96813 USA.
EM cvogel@cc.hawaii.edu
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NR 141
TC 22
Z9 29
U1 0
U2 7
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
PY 2014
VL 61
IS 2
SI SI
BP 191
EP 203
DI 10.1016/j.molimm.2014.06.035
PG 13
WC Biochemistry & Molecular Biology; Immunology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biochemistry & Molecular Biology; Immunology
GA AP7NZ
UT WOS:000342265300017
PM 25062833
DA 2022-11-30
ER

PT J
AU Zhou, QB
   Anderson, C
   Zhang, HM
   Li, XY
   Inglis, F
   Jayagopal, A
   Wang, SS
AF Zhou, Qinbo
   Anderson, Chastain
   Zhang, Hongmei
   Li, Xinyu
   Inglis, Fiona
   Jayagopal, Ashwath
   Wang, Shusheng
TI Repression of Choroidal Neovascularization Through Actin Cytoskeleton
   Pathways by MicroRNA-24
SO MOLECULAR THERAPY
LA English
DT Article
ID MACULAR DEGENERATION; DOWN-REGULATION; MYOCARDIAL-INFARCTION;
   CELL-PROLIFERATION; ENDOTHELIAL-CELLS; CANCER-CELLS; ANGIOGENESIS;
   RANIBIZUMAB; DIFFERENTIATION; APOPTOSIS
AB Actin cytoskeleton is critical for cell motility and division, both of which are important for angiogenesis. MicroRNAs (miRNA/miR) are emerging as pivotal modulators of vascular development and disease. How miRNAs regulate actin cytoskeleton dynamics in endothelial cells (EC) and neovascularization is still unclear. Here, we report that miR-24 regulates actin dynamics in ECs through targeting multiple members downstream of Rho signaling, including Pak4, Limk2, and Diaphl proteins. Overexpression of miR-24 in ECs blocks stress fiber and lamellipodia formation, represses EC migration, proliferation, and tube formation in vitro, as well as angiogenesis in an ex vivo aortic ring assay. Moreover, subretinal delivery of miR-24 mimics represses laser-induced choroidal neovascularization (CNV) in vivo. Mechanistically, knockdown of miR-24 target protein LIMK2 or PAK4 inhibits stress fiber formation and tube formation in vitro, mimicking miR-24 overexpression phenotype in angiogenesis, while overexpression of LIMK2 and PAK4 by adenoviruses partially rescued the tube formation defects in miR-24 over-expressing ECs. Taken together, these findings suggest that miR-24 represses angiogenesis by simultaneously regulating multiple components in the actin cytoskeleton pathways. Manipulation of actin cytoskeleton pathways by miR-24 may represent an attractive therapeutic solution for the treatment of wet age-related macular degeneration (AMD) and other vascular diseases.
C1 [Zhou, Qinbo; Anderson, Chastain; Inglis, Fiona; Wang, Shusheng] Tulane Univ, Dept Cell & Mol Biol, New Orleans, LA 70118 USA.
   [Zhang, Hongmei; Li, Xinyu] Univ Texas SW Med Ctr Dallas, Dept Ophthalmol, Dallas, TX 75390 USA.
   [Jayagopal, Ashwath] Vanderbilt Univ, Med Ctr, Dept Ophthalmol & Visual Sci, Nashville, TN USA.
   [Wang, Shusheng] Tulane Univ, Dept Ophthalmol, New Orleans, LA 70118 USA.
C3 Tulane University; University of Texas System; University of Texas
   Southwestern Medical Center Dallas; Vanderbilt University; Tulane
   University
RP Wang, SS (通讯作者)，Tulane Univ, Dept Cell & Mol Biol, New Orleans, LA 70118 USA.
EM swang1@tulane.edu
OI Li, Xinyu/0000-0002-5908-6676; Zhou, Qinbo/0000-0002-7967-2138
FU Startup fund from Tulane University; UT Southwestern Medical Center
   [EY021862]; American Heart Association Southeast Affiliate Postdoctoral
   fellowship; NATIONAL EYE INSTITUTE [R01EY021862, R01EY023397] Funding
   Source: NIH RePORTER
FX We are grateful to Eric Olson for his encouragement of the project. S.W.
   was supported by a Startup fund from Tulane University, President's
   Research Council New Investigator Award from UT Southwestern Medical
   Center, NIH Grant EY021862, a career development award from the Research
   to Prevent Blindness foundation, and a Bright Focus Foundation Award in
   age-related macular degeneration. Q.Z. was supported by an American
   Heart Association Southeast Affiliate Postdoctoral fellowship. The
   authors declare no fanancial conflict of interest related to the
   submitted manuscript.
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NR 46
TC 47
Z9 51
U1 0
U2 14
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD FEB
PY 2014
VL 22
IS 2
BP 378
EP 389
DI 10.1038/mt.2013.243
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA 304NP
UT WOS:000330753900019
PM 24297048
OA Green Published, hybrid
DA 2022-11-30
ER

PT J
AU Ng, TK
   Yam, GHF
   Chen, WQ
   Lee, VYW
   Chen, HY
   Chen, LJ
   Choy, KW
   Yang, ZL
   Pang, CP
AF Ng, Tsz Kin
   Yam, Gary H. F.
   Chen, Wei Qi
   Lee, Vincent Y. W.
   Chen, Haoyu
   Chen, Li Jia
   Choy, Kwong Wai
   Yang, Zhenglin
   Pang, Chi Pui
TI Interactive Expressions of HtrA1 and VEGF in Human Vitreous Humors and
   Fetal RPE Cells
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; SERINE-PROTEASE HTRA1; EPITHELIUM-DERIVED
   FACTOR; MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; PROMOTER
   POLYMORPHISM; ANGIOGENESIS; VARIANTS; STRESS; INFLAMMATION
AB PURPOSE. High-temperature requirement factor A1 (HtrA1) is associated with exudative age-related macular degeneration, an angiogenic retinal disease related to vascular endothelial growth factor (VEGF). This study investigates the interactive relationship between the expressions of HtrA1 and VEGF.
   METHODS. The vitreous humor levels of HtrA1, VEGF, and pigment epithelium-derived factor were determined in 55 unrelated Han Chinese patients who underwent ocular surgeries. Expressions of HTRA1 and VEGFA were studied interactively and under stress conditions in primary human fetal retinal pigment epithelial (RPE) cells to evaluate their regulations.
   RESULTS. Vitreous levels of HtrA1 were significantly associated with that of VEGF in vitreous samples from all patients (Pearson's correlation coefficient test, r = 0.650, P = 7.91 x 10(-8)) and from patients with retinal detachment (r = 0.835, P = 2.14 x 10(-7)). On stress induction, HTRA1 and VEGFA were upregulated in human fetal RPE cells treated by tunicamycin and dithiothreitol, but reduced after treatment by MG132. However, HtrA1 and VEGF did not regulate each other in their expressions.
   CONCLUSIONS. This study revealed an association between HtrA1 and VEGF in human vitreous humors and RPE cells. They are both related to stress and inflammatory conditions. (Invest Ophthalmol Vis Sci. 2011;52:3706-3712) DOI: 10.1167/iovs.10-6773
C1 [Ng, Tsz Kin; Yam, Gary H. F.; Lee, Vincent Y. W.; Chen, Li Jia; Pang, Chi Pui] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Kowloon, Hong Kong, Peoples R China.
   [Choy, Kwong Wai] Chinese Univ Hong Kong, Dept Obstet & Gynaecol, Kowloon, Hong Kong, Peoples R China.
   [Chen, Wei Qi; Chen, Haoyu] Shantou Univ, Joint Shantou Int Eye Ctr, Shantou, Peoples R China.
   [Chen, Wei Qi; Chen, Haoyu] Chinese Univ Hong Kong, Shantou, Peoples R China.
   [Yang, Zhenglin] Sichuan Acad Med Sci, Ctr Human Mol Biol & Genet, Chengdu, Sichuan, Peoples R China.
   [Yang, Zhenglin] Sichuan Prov Peoples Hosp, Chengdu, Sichuan, Peoples R China.
C3 Chinese University of Hong Kong; Chinese University of Hong Kong;
   Shantou University; Sichuan Provincial People's Hospital; Sichuan
   Provincial People's Hospital
RP Pang, CP (通讯作者)，Chinese Univ Hong Kong, Hong Kong Eye Hosp, Dept Ophthalmol & Visual Sci, 147K Argyle St, Kowloon, Hong Kong, Peoples R China.
EM cppang@cuhk.edu.hk
RI Ng, Tsz Kin/I-8061-2014; Chen, Li Jia/I-5078-2014; Yam, Gary
   Hin-Fai/ABE-1710-2020; Pang, Chi P/I-5388-2014; Choy,
   Richard/AAW-8230-2020; Chen, Haoyu/A-7432-2013
OI Ng, Tsz Kin/0000-0001-7863-7229; Chen, Li Jia/0000-0003-3500-5840; Choy,
   Richard/0000-0002-3616-6200; Chen, Haoyu/0000-0003-0676-4610
FU University Grants Committee Hong Kong; Endowment Fund for Lim Por-Yen
   Eye Genetics Research Centre, Hong Kong
FX Supported in part by a block grant of the University Grants Committee
   Hong Kong and the Endowment Fund for Lim Por-Yen Eye Genetics Research
   Centre, Hong Kong.
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NR 56
TC 17
Z9 18
U1 0
U2 7
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAY
PY 2011
VL 52
IS 6
BP 3706
EP 3712
DI 10.1167/iovs.10-6773
PG 7
WC Ophthalmology
WE Science Citation Index Expanded (SCI-EXPANDED)
SC Ophthalmology
GA 800CF
UT WOS:000293335400037
PM 21310902
DA 2022-11-30
ER

EF