Activation of GSDME by all-<i>trans</i>-retinal increases sensitivity to photoreceptor ferroptosis.

ABSTRACT: Impaired clearance of all-trans-retinal (atRAL) due to visual cycle dysfunction contributes to photoreceptor atrophy, a key pathological hallmark of Stargardt disease type 1 (STGD1) and dry age-related macular degeneration (AMD). Prior studies have shown that light-induced atRAL accumulation promotes ferroptosis and activates gasdermin E (GSDME) in retinal photoreceptors of Abca4^-/-Rdh8^-/- mice, a model for STGD1 and dry AMD that exhibits visual cycle disorders. However, the role of GSDME in photoreceptor ferroptosis remains unclear. In this study, we revealed that GSDME activation by atRAL triggered photoreceptor ferroptosis and retinal atrophy via mitochondrial damage and oxidative stress. Knocking out GSDME significantly attenuated light-induced photo

SUBMITTER: Yang B 

PROVIDER: S-EPMC12631243 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature