Sodium Iodate-Induced Ferroptosis in Photoreceptor-Derived 661W Cells Through the Depletion of GSH.

Oxidative stress-induced photoreceptor cell death is closely associated with the etiology of age-related macular degeneration (AMD), and sodium iodate (SI) has been widely used as an oxidant stimulus in AMD models to induce retinal pigment epithelium (RPE) and photoreceptor cell death. However, the mechanism underlying SI-induced photoreceptor cell death remains controversial and unclear. In this study, we elucidate that ferroptosis is a critical form of cell death induced by SI in photoreceptor-derived 661W cells. SI disrupts system Xc, leading to glutathione (GSH) depletion and triggering lipid peroxidation, thereby promoting ferroptosis in photoreceptor-derived 661W cells. Additionally, SI enhances intracellular Fe levels, which further facilitates reactive oxygen species (ROS) accumulation, making the 661W cells more susceptible to ferroptosis. Exogenous GSH, as well as specific inhibitors of ferroptosis such as Fer-1 and antioxidants like NAC, significantly attenuate SI-induced ferroptosis in photoreceptor-derived 661W cells. These findings provide new insights into the mechanisms of ferroptosis as a key pathway in SI-induced photoreceptor-derived 661W cell death.