Korean J Perinatol.  2011 Mar;22(1):10-21.

The Effects of Resveratrol via Mediation of Nitric Oxide Synthase (NOS) on Hypoxic Retinal Injury in Neonatal Rats

• Han YH
• Ju M
• Choi EJ
• Kim JK
• Chung HL
• Kim WT

Abstract

PURPOSE
Retinopathy of prematurity (ROP) is one of the leading causes of blindness, with retinal detachment occurring due to oxygen toxicity in preterm infants. After premature delivery, oxygen levels are significantly increased compared to those in utero and oxygen therapy further increases oxygen levels in the developing retina. This hyperoxia results in reducing vascular endothelial growth factor (VEGF) level. After the cessation of oxygen therapy and the return to normal oxygen levels, the nonperfused portions of the retina become hypoxic. Retinal hypoxia stimulates VEGF which causes retinal neovascularization and retinal proliferation. Further inhibition of VEGF decreases retinal neovascularization. Recently, resveratrol was found to protect the spinal cord, kidney, and heart from ischemia-reperfusion injury through upregulation of nitric oxide (NO). Resveratrol has been reported to either suppress or enhance NO production. Resveratrol inhibits nitric oxide synthase (NOS) activity and modifies inducible nitric oxide synthase (iNOS) expression. In the present study, we aimed to determine whether or not resveratrol exhibits protective effects via mediation of NOS after a hypoxic retinal insult.
METHODS
In the in vitro hypoxic retinal injury, primary retinal cell culture was performed using P0-2 Sprague-Dawley (SD) rats. Hypoxia insults were induced through 1% O2 exposure for sixteen hours. Western blotting and real-time PCR using iNOS, endothelia nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS) antibodies and mRNAs were performed.
RESULTS
The expressions of iNOS antibody and mRNA were reduced after a hypoxic insult, whereas it was recovered after treatment with resveratrol. In contrast, those of eNOS and nNOS showed reversely.
CONCLUSION
Resveratrol appeared to exert retinal protective effects via mediation of NOS on hypoxic retinal injury in neonatal rats.

Keyword

Nitric oxide synthase; Resveratrol; Hypoxic retinal injury

MeSH Terms

Animals
Anoxia
Antibodies
Blindness
Blotting, Western
Cell Culture Techniques
Heart
Humans
Hyperoxia
Infant, Newborn
Infant, Premature
Kidney
Negotiating
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type II
Oxygen
Rats
Real-Time Polymerase Chain Reaction
Reperfusion Injury
Retina
Retinal Detachment
Retinal Neovascularization
Retinaldehyde
Retinopathy of Prematurity
RNA, Messenger
Spinal Cord
Stilbenes
Up-Regulation
Vascular Endothelial Growth Factor A
Antibodies
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type II
Oxygen
RNA, Messenger
Retinaldehyde
Stilbenes
Vascular Endothelial Growth Factor A