Ferroptosis drives photoreceptor degeneration in mice with defects in all-trans-retinal clearance.

ABSTRACT: The death of photoreceptor cells in dry age-related macular degeneration (AMD) and autosomal recessive Stargardt disease (STGD1) is closely associated with disruption in all-trans-retinal (atRAL) clearance in neural retina. In this study, we reveal that the overload of atRAL leads to photoreceptor degeneration through activating ferroptosis, a nonapoptotic form of cell death. Ferroptosis of photoreceptor cells induced by atRAL resulted from increased ferrous ion (Fe²⁺), elevated ACSL4 expression, system Xc^- inhibition, and mitochondrial destruction. Fe²⁺ overload, tripeptide glutathione (GSH) depletion, and damaged mitochondria in photoreceptor cells exposed to atRAL provoked reactive oxygen species (ROS) production, which, together with ACSL4 activation, p

SUBMITTER: Chen C 

PROVIDER: S-EPMC7948481 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature