Flavonoids Protect Retinal Ganglion Cells from Oxidative Stress–Induced Death

Abstract

PURPOSE: Mounting evidence suggests that oxidative stress contributes to the pathogenesis of many ocular diseases, including glaucoma and diabetic retinopathy. No treatments are available to prevent the neuronal degeneration that occurs in these disorders. The purpose of this study was to determine whether flavonoids, natural products that are abundant in fruits and vegetables, can protect retinal ganglion cells from oxidative stress-induced death. METHODS: The ability of flavonoids to protect an immortalized retinal ganglion cell line, RGC-5 cells, was tested using three model systems of oxidative stress-induced cell death: glutathione (GSH) depletion, t-butyl peroxide (t-BOOH) treatment, and hydrogen peroxide (H2O2) treatment. RESULTS: GSH depletion causes retinal ganglion cell death by a pathway involving the production of endogenous reactive oxygen species (ROS), whereas the other two treatments use exogenous sources of ROS. It was found that specific flavonoids could protect retinal ganglion cells from cell death initiated by all three of the inducers of oxidative stress with high levels of potency and low toxicity. In the case of GSH depletion, different flavonoids could be shown to act at distinct steps in the cell death pathway. Several of the protective flavonoids also induced the synthesis of the transcription factor NF-E2-related factor 2 and phase 2 antioxidant enzymes such as heme oxygenase 1, markers for the activation of the antioxidant response element. CONCLUSIONS: These results suggest that certain flavonoids can function as potent and effective neuroprotective agents for retinal ganglion cells.