Asparagine alleviates naphthalene-induced lens opacity by suppressing ferroptosis

Cataract, with lens opacity as its feature, often cause vision loss. The main clinical treatment is lens replacement surgery, which usually works well for most of the patients, but not for all. And researching drugs to delay or treat cataracts is also very important socially and scientifically. This study explored the effect of asparagine (Asn) on cataracts. In vivo, a naphthalene-induced cataract model in rats was set up, focusing on lens opacity. In vitro, SRA01/04 cells or cultured lenses were treated with the naphthalene metabolite 1,2-dihydroxynaphthalene (1,2-DHN) to study cellular mechanisms. The results showed that Asn effectively reduced lens opacity in rats with naphthalene-induced cataracts. In vitro experiments revealed that the ATF3/GPX4 signaling pathway is involved in the mechanism by which asparagine inhibits ferroptosis in lens epithelial cells induced by 1,2-DHN, playing a crucial role in this process. When given orally, Asn could cut down the accumulation of ferrous ions caused by naphthalene, stop the production of reactive oxygen species (ROS) and malondialdehyde (MDA), and ease the depletion of glutathione (GSH). In short, our findings suggest that Asn can protect against naphthalene-induced cataracts by reducing ferroptosis. This new discovery surely creates new research directions and strategies for future cataract prevention and treatment.