Clinical Ophthalmology (Mar 2022)
A Plant-Derived Antioxidant Supplement Prevents the Loss of Retinal Ganglion Cells in the Retinas of NMDA-Injured Mice
Abstract
Shigeto Maekawa,1 Kota Sato,1,2 Taiki Kokubun,1 Noriko Himori,1,3 Takeshi Yabana,1 Michiko Ohno-Oishi,1 Ge Shi,1 Kazuko Omodaka,1,4 Toru Nakazawa1,2,4– 6 1Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan; 2Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan; 3Department of Aging Vision Healthcare, Tohoku University Graduate School of Biomedical Engineering, Sendai, Miyagi, Japan; 4Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan; 5Collaborative Program for Ophthalmic Drug Discovery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan; 6Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, Sendai, Miyagi, JapanCorrespondence: Toru Nakazawa, Department of Ophthalmology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, Miyagi, 980-8574, Japan, Tel +81-22-717-7294, Fax +81-22-717-7298, Email [email protected]: 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 administrated 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.Keywords: plant-derived antioxidant compounds, oxidative stress, retinal ganglion cells, glaucoma
