Flavonoids protect retinal ganglion cells from oxidative stress–induced cell death

Abstract

Abstract: : Purpose: Mounting evidence suggests that oxidative stress contributes to the pathogenesis of many ocular diseases, including glaucoma, diabetes and macular degeneration. No treatments are available to prevent the neuronal degeneration which occurs in these disorders. The purpose of our study was to understand how oxidative stress kills retinal ganglion cells (RGCs) and to identify compounds which protect cells from oxidative stress–induced cell death. Methods: We tested the ability of flavonoids to protect RGC–5 cells using two model system of oxidative stress–induced cell death, i) glutathione depletion and ii) t–butyl peroxide treatment. Results: Glutathione depletion causes RGC death by a pathway involving the production of reactive oxygen species and the influx of extracellular calcium. This pathway is distinct from classical apoptosis. We found that low micromolar levels of several different flavonoids could protect RGCs from death induced by glutathione depletion and t–butyl peroxide treatment. More importantly, protection was seen even when the flavonoids were added after the initial oxidative insult. Conclusions: These results suggest that consumption of specific flavonoids could have beneficial effects on the eye in both pathological conditions and in normal aging.

Keywords: neuroprotection • oxidation/oxidative or free radical damage • ganglion cells