A Plant-Derived Antioxidant Supplement Prevents the Loss of Retinal Ganglion Cells in the Retinas of NMDA-Injured Mice

Abstract

Purpose: To investigate the effect of plant-derived antioxidant compounds, identified with primary culture screening, on retinal ganglion cell (RGC) survival in mice under excitotoxic conditions. Additionally, to determine the effect of these compounds on the involvement of calpain inactivation. Materials and Methods: Plant-derived antioxidant compounds including hesperidin, crocetin, and Tamarindus indica were admini-strated orally to C57BL/6J mice. The levels of lipid oxidation and calpain activation were assessed with a TBARS assay and western blotting. RGC survival was evaluated with a TUNEL assay and RBPMS immunostaining after intravitreal injection of NMDA. Results: Plant-derived antioxidant compounds significantly ameliorated the increase in the level of MDA in the retinas after NMDA injury. Cleaved α-fodrin fragments were detected in the NMDA-injured retinas, and these fragments were significantly lower in mice that received the plant-derived antioxidant compounds. The plant-derived antioxidants also ameliorated increases in TUNEL-positive cells and RGC death after NMDA injection. Conclusion: These results indicate that oral administration of plant-derived antioxidant compounds such as hesperidin, crocetin, and Tamarindus indica suppressed RGC death. This oral supplementation decreased lipid oxidation and excessive calpain activation in NMDA-injured retinas. Thus, our newly developed antioxidant supplement has a potential role in neuroprotective treatment for retinal diseases, such as glaucoma.