Resveratrol mitigates rat retinal ischemic injury: the roles of matrix metalloproteinase-9, inducible nitric oxide, and heme oxygenase-1.
OBJECTIVE
Retinal ischemia-associated ocular disorders, such as retinal occlusive disorders, neovascular age-related macular degeneration, proliferative diabetic retinopathy, and glaucoma are vision-threatening. In this study, we examined whether and by what mechanisms resveratrol, a polyphenol found in red wine, is able to protect against retinal ischemia/reperfusion injury.


METHODS
In vivo rat retinal ischemia was induced by high intraocular pressure (HIOP), namely, 120 mmHg for 60 min. The mechanism and management was evaluated by electroretinogram (ERG) b-wave amplitudes measurement, immunohistochemistry, and real-time polymerase chain reaction.


RESULTS
The HIOP-induced retinal ischemic changes were characterized by a decrease in ERG b-wave amplitudes, a loss of choline acetyltransferase immunolabeling of amacrine cell bodies/neuronal processes, and increased vimentin immunoreactivity, which is a marker of Müller cells, together with upregulation of matrix metalloproteinase-9 (MMP-9), heme oxygenase-1 (HO-1), and inducible nitric oxide (iNOS), and downregulation of Thy-1, both at the mRNA level. The detrimental effects due to the ischemia were concentration-dependent (weaker effect at 0.05 nmole) and/or significantly (at 0.5 nmole) altered when resveratrol was applied 15 min before or after retina ischemia.


CONCLUSIONS
This study supports the hypothesis that resveratrol may be able to protect the retina against ischemia by downregulation of MMP-9 and iNOS, and upregulation of HO-1.
Department of Pharmacology, School of Medicine, Shandong University , Jinan, Shandong, People's Republic of China.
Xiao-Qian
XQ
Liu
Bing-Jhih
BJ
Wu
Wynn H T
WH
Pan
Xiu-Mei
XM
Zhang
Jorn-Hon
JH
Liu
Mi-Mi
MM
Chen
Fang-Ping
FP
Chao
Hsiao-Ming
HM
Chao
D000818:Animals; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004596:Electroretinography; D051547:Heme Oxygenase-1 / Q000235:genetics; D007429:Intraocular Pressure; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D000077185:Resveratrol; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D012171:Retinal Vessels / Q000187:drug effects* / Q000473:pathology; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology*; D018800:Thy-1 Antigens / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects; D014746:Vimentin / Q000276:immunology
D012333:RNA, Messenger; D013267:Stilbenes; D018800:Thy-1 Antigens; D014746:Vimentin; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D020780:Matrix Metalloproteinase 9; D000077185:Resveratrol