Glutathione Protects Human Retinal Pigment Epithelial Cells From Lipopolysaccharide-Induced Apoptosis and Oxidative Stress by Inhibiting The TRPM2 Channel

Gram-negative bacteria's outer membranes include lipopolysaccharides (LPS), which are a major contributor to inflammatory eye disorders. LPS cause apoptosis induction and produce reactive free radicals of oxygen (ROS). In microglia, LPS-induced ROS stimulates transient receptor melastatin 2 (TRPM2), whereas glutathione (GSH) and N-(p-amylcinnamoyl) anthranilic acid (ACA) decrease their activation. Anti-apoptotic and antioxidant properties of GSH through TRPM2 inhibition were not reported in human retinal pigment epithelial (ARPE-19) cells. Therefore, the modulator action of GSH on the TRPM2-mediated molecular oxidant and apoptotic pathways in ARPE-19 was investigated. Five main groups were generated in the ARPE-19: Control, GSH (10 mM for 2 h), LPS (1 μg/ml for 24 h), LPS + GSH, and LPS + ACA (25 μM for 30 min). The amounts of ROS, mitochondrial dysfunction, apoptosis, caspases (caspase-3, -8, and -9), and cytosolic free Ca2+ were increased by the LPS incubation, while the incubations of GSH and ACA reduced their amounts. The viable cell number and viability percentage were decreased by LPS, but their viability and number were increased by the incubations of GSH and ACA. In conclusion, GSH decreased the levels of LPS caused oxidative stress and apoptosis via suppressing TRPM2 in the ARPE-19. One possible treatment agent for oxidative retinal injury and inflammatory eye diseases induced by LPS could be the GSH treatment.