Exp Eye Res. 2025 Sep 17:110647. doi: 10.1016/j.exer.2025.110647. Online ahead of print.
ABSTRACT
Corneal endothelial decompensation is a common vision-threatening disease, with a diverse range of pathogenic factors, ultimately necessitating corneal transplantation. Corneal endothelial cells (CECs) act as a barrier between the aqueous humor and stroma, and are non-proliferative in vivo. CECs are susceptible to oxidative stress damage due to their lifelong high metabolic state, which enables them to constantly pump liquid to maintain the dehydrated status of the cornea. Consequently, CECs are subjected to the accumulation of oxidative stress over time, which can result in cell death in the form of apoptosis. In this study, we identified ferroptosis of CECs as a nonapoptotic pathological process in the ultraviolet A (UVA)-mediated corneal endothelial decompensation, confirmed by the production of lipid peroxidation and the observed morphological changes in the mitochondria. The process was mediated by the promotion of nuclear export of nuclear erythroid 2-related factor 2 (Nrf-2). In addition, we identified for the first time that a natural iron chelator, phytic acid (PA), could protect CEC from UVA-mediated ferroptosis and helped to maintain the function of corneal endothelium. Our findings suggest that PA has the potential as a therapeutic agent for the treatment of corneal endothelial decompensation.
PMID:40972858 | DOI:10.1016/j.exer.2025.110647