Astaxanthin ameliorates oxidative stress in lens epithelial cells by regulating GPX4 and ferroptosis

Ferroptosis is a form of regulated cell death closely associated with oxidative stress and mitochondrial dysfunction and is characterised by the accumulation of reactive oxygen species (ROS) and lipid species and iron overload. Damage to human lens epithelial cells (LECs) is associated with age-related cataract progression. Astaxanthin (ATX), a carotenoid with natural antioxidant properties, counteracts ferroptosis in the treatment of various degenerative diseases. However, this mechanism has not been reported with respect to cataract treatment. In this study, the differential expression levels of glutathione peroxidase 4 (GPX4) in the lens of young and aged mice were analysed. Continuous ATX supplementation for 8 months upregulated GPX4 expression in the mouse LECs and delayed the progression of ferroptosis. Upon treatment with erastin, ROS and malondialdehyde accumulated and the mitochondrial membrane potential decreased. At the same time, the expressions of GPX4, SLC7A11, and ferritin were suppressed in human LECs. All of these phenomena were partially reversed by ATX and Fer-1, a ferroptosis inhibitor. This study confirmed that the ATX-mediated targeting of GPX4 might alleviate human LECs damage by inhibiting ferroptosis and ameliorating oxidative stress and that this could represent a promising therapeutic approach for age-related cataract.