Neuroprotective Effect of Resveratrol on Experimental Retinal Ischemic Injury

Abstract

 

Purpose:

 

Resveratrol has been reported to have anti-inflammatory, anti-aging, antioxidant, and anti-tumor activities. Studies have demonstrated protective effects in the spinal cord, kidneys, heart, and brain from ischemia-reperfusion injury. In this study, we investigated the neuroprotective effects of resveratrol in vitro on glutamate-induced cytotoxicity in R28 retinal precursor cells and in vivo using a pressure-induced retinal ischemic model.

 

Methods:

 

For in vitro studies, confluent cultures of R28 cells were treated with L-glutamate (0-6 mM) for 24 hours in the absence or presence of resveratrol (1-2 µg/ml). Cell viability after treatment was determined with a neutral red dye uptake assay. For in vivo studies, retinal ischemia was induced in adult male Sprague Dawley rats by intracameral elevation of intraocular pressure for 45 minutes. Following ischemic insult, rats received (intraperitoneally) an equal volume of vehicle (20% DMSO) or resveratrol (20 mg/kg) daily for 6 days. Retinal function was determined by relative changes in electroretinographic (ERG) responses from dark-adapted rats assessed prior to and 7 days after ischemic insult.

 

Results:

 

In vitro, glutamate treatment (6 mM) resulted in R28 cell death and decreased cell viability to 36±3%. The addition of resveratrol protected against glutamate-induced cytotoxicity; cell viability improved to 68±3% (1 µg/ml) and 70±6% (2 µg/ml). In vivo, prior to ischemic insult, scotopic ERG a- and b-wave amplitudes were statistically similar between the two treatment groups (average a-wave 417±51 µV and b-wave 817±90 µV). Following ischemic-reperfusion injury, ERG a- and b-wave amplitudes in vehicle-treated rats were 49±8 µV and 86±38 µV, respectively. By comparison, post-ischemia ERG a- and b-wave amplitudes in resveratrol-treated rats were 139±14 µV and 181±40 µV, respectively.

 

Conclusions:

 

Resveratrol protects cultured R28 cells against glutamate-induced cell cytotoxicity in vitro. In vivo, resveratrol-treated rats showed marked improvement in ERG a-wave and b-wave amplitudes following ischemic insult. These preliminary findings suggest that resveratrol has therapeutic value in the management of retinal ischemic diseases.

 

Keywords: ischemia • neuroprotection • drug toxicity/drug effects