Retinal Protective Effects of Resveratrol via Modulation of Nitric Oxide Synthase on Oxygen-induced Retinopathy

Abstract

PurposeRetinopathy of prematurity (ROP) is one of the leading causes of blindness, with retinal detachment occurring due to oxygen toxicity in preterm infants. Recently, advances in neonatal care have led to improved survival rates for preterm infants, and ROP has increased in incidence. In the present study, we aimed to determine whether or not resveratrol exhibits protective effects in an animal model of ROP and in primary retinal cell cultures of neonatal rat via nitric oxide (NO)-modulating actions using western blotting and real-time PCR with inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS) and neuronal NOS (nNOS) antibodies and mRNAs.MethodsIn an in vivo oxygen-induced retinopathy (OIR) model, cyclic hyperoxia was induced with 80% O2 for one day and 21% O2 for one day from P1 to P14 in newborn Sprague-Dawley (SD) rats. Resveratrol was injected intravitreally for seven days and rats were sacrificed at P21. In vitro OIR primary retinal cell culture was performed using P0-2 SD rats. Hyperoxia injuries were induced through 100% O2 exposure for six hours. Western blotting and real-time PCR using iNOS, eNOS, nNOS antibodies and primers were performed in the rat model of ROP and the dispersed retinal cell culture.ResultsIn both in vivo and in vitro OIR, the expression of iNOS antibody and mRNA was increased and of eNOS and nNOS were reduced in the resveratrol-treated group.ConclusionsIn conclusion, resveratrol appeared to exert retinal protective effects via modulation of NO-mediated mechanism in in vivo and in vitro OIR models.

Resveratrol alleviates endotoxemia-associated adrenal insufficiency by suppressing oxidative/nitrative stress

“…Resveratrol also restores the reduced retinal iNOS expression in a rat model of oxygen-induced retinopathy [35]. Moreover, resveratrol increase iNOS activity in primary cultured rat vascular smooth muscle cells [36].…”

Resveratrol Mitigates Rat Retinal Ischemic Injury: The Roles of Matrix Metalloproteinase-9, Inducible Nitric Oxide, and Heme Oxygenase-1

“…In the process, high levels of NO have the opportunity to react with superoxide leading to peroxynitrite formation and cell toxicity. 1,2,13 Resveratrol appeared to exert retinal protective effects via modulation of NOS in oxygen-induced retinopathy. 13 Oxidative stress damage plays a vital role in retinal ischemia/ reperfusion (I/R) pathogenesis.…”

“…1,2,13 Resveratrol appeared to exert retinal protective effects via modulation of NOS in oxygen-induced retinopathy. 13 Oxidative stress damage plays a vital role in retinal ischemia/ reperfusion (I/R) pathogenesis. Therefore, the possibility of an antioxidant therapy that is able to reduce I/R induced damage attracted our intense interest.…”

Effects of a Rho kinase inhibitor on the sequential expression of ICAM-1, HIF-1α, Bcl-2 and caspase-3 in the retina of rats with oxygen-induced retinopathy

“…Another study indicated that ROCK inhibitors promote VEGF-mediated proliferation and the neovascularization of endothelial cells in vitro (24). In the present study, we established a rat model of OIR as previously described (25)(26)(27)(28) to determine whether ROCK affects retinal neovascularization and to determine the effects of the ROCK inhibitor, FSD, on the expression of ICAM-1, HIF-1α, Bcl-2 and caspase-3. Using this model, we observed the NP region and retinal blood vessel networks around the optic nerve, examined the mRNA expression of ICAM-1, Bcl-2, caspase-3 and HIF-1α in samples from 3 treatment groups at different time points, and assessed the effects of FSD on the NP region and vascularization in the retina of rats with OIR.…”

“…Using this model, we observed the NP region and retinal blood vessel networks around the optic nerve, examined the mRNA expression of ICAM-1, Bcl-2, caspase-3 and HIF-1α in samples from 3 treatment groups at different time points, and assessed the effects of FSD on the NP region and vascularization in the retina of rats with OIR. We implemented a cyclic oxygen exposure protocol that was modified from previous studies on oxygen-induced retinopathy using rats (25)(26)(27). Hyperoxic experiments were conducted in an airtight glass container constructed in our laboratory.…”