Resveratrol mitigates rat retinal ischemic injury: the roles of matrix metalloproteinase-9, inducible nitric oxide, and heme oxygenase-1

J Ocul Pharmacol Ther. 2013 Feb;29(1):33-40. doi: 10.1089/jop.2012.0141. Epub 2012 Oct 17.


Purpose: 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.

Conclusion: 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.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Electroretinography
  • Heme Oxygenase-1 / genetics
  • Intraocular Pressure
  • Matrix Metalloproteinase 9 / genetics
  • Nitric Oxide Synthase Type II / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / pathology
  • Resveratrol
  • Retina / drug effects*
  • Retina / pathology
  • Retinal Vessels / drug effects*
  • Retinal Vessels / pathology
  • Stilbenes / administration & dosage
  • Stilbenes / pharmacology*
  • Thy-1 Antigens / genetics
  • Up-Regulation / drug effects
  • Vimentin / immunology


  • RNA, Messenger
  • Stilbenes
  • Thy-1 Antigens
  • Vimentin
  • Nitric Oxide Synthase Type II
  • Heme Oxygenase-1
  • Matrix Metalloproteinase 9
  • Resveratrol