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

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.