Invest Ophthalmol Vis Sci. 2025 Dec 1;66(15):58. doi: 10.1167/iovs.66.15.58.
ABSTRACT
PURPOSE: The purpose of this study was to investigate the role of glutaredoxin 2 (Grx2) in regulating ferroptosis under oxidative stress conditions induced by high glucose in lens epithelial cells (LECs) and its potential contribution to diabetes-mediated cataractogenesis.
METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to investigate proteins S-glutathionylation under high glucose condition, with validation by co-immunoprecipitation (Co-IP). Lentiviral transduction, Western blotting, FerroOrange, reactive oxygen species (ROS), and glutathione (GSH) measurements were applied to elucidate the downstream mechanisms.
RESULTS: High glucose-induced oxidative stress triggered ferroptosis in the LECs, thereby accelerating diabetes-mediated cataractogenesis. LC-MS/MS and Co-IP analysis identified HNRNPA2B1 as a Grx2-regulated target protein exhibiting increased glutathionylation. This modification regulated PTEN/AKT signaling, leading to mitochondrial dysfunction and subsequent ferroptosis induction.
CONCLUSIONS: Grx2 exerts protective effects against ferroptosis in diabetes-mediated cataractogenesis by inhibiting HNRNPA2B1 S-glutathionylation and modulating PTEN/AKT signaling pathway.
PMID:41533928 | DOI:10.1167/iovs.66.15.58