Protective effects of empagliflozin against NMDA-induced excitotoxicity in the rat retina.

Empagliflozin (EMPA), a sodium-glucose cotransporter 2 inhibitor used in patients with type 2 diabetes, exerts various beneficial effects, including anti-inflammatory and antioxidant properties, in addition to its glucose-lowering effect. In this study, we examined whether EMPA protects against N-methyl-d-aspartic acid (NMDA)-induced retinal excitotoxicity and the mechanisms underlying its protective effects. Male Sprague-Dawley rats (7-8 weeks old) were used in this study. The number of cells in the ganglion cell layer (GCL) decreased 7 days after intravitreal injection of NMDA (50 nmol). Simultaneous intravitreal injection of EMPA (50 and 100 nmol) and NMDA reduced NMDA-induced cell loss in a dose-dependent manner. The protective effect of EMPA was significantly attenuated by the AMP-activated protein kinase (AMPK) inhibitor, compound C (10 nmol). NMDA increased the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells in the GCL 6 h after injection, and the response was significantly, but not completely, attenuated by EMPA. These results suggest that EMPA protects against NMDA-induced retinal excitotoxicity in rats. The protective effect of EMPA may be partly attributed to the activation of the AMPK pathway and inhibition of neuronal cell apoptosis.