Fe-curcumin nanozymes-mediated reactive oxygen species scavenging and anti-apoptotic effects on age-related cataracts
Xiang Gao, Kewei Li, Yan Huang, Ziyan Long, Yongguo Xiang, Wendi Zheng, Hong Cheng, Huijie Cao, Wenjuan Wan, S. J. Zheng, Xianwen Wang, Ke Hu
Abstract
Age-related cataracts (ARCs) are major causes of vision impairment globally, primarily resulting from oxidative stress–induced senescence and apoptosis in lens epithelial cells (LECs). In this study, a sodium selenite-induced oxidative stress cataract model in neonatal rats was used to mimic ARC pathology. We investigated the therapeutic potential of Fe-curcumin nanozymes in delaying ARC progression by targeting cellular senescence and oxidative injury. In vitro experiments revealed that Fe-curcumin nanozymes significantly reduced reactive oxygen species (ROS) levels in H 2 O 2 -treated LECs, alleviated cellular senescence, and decreased apoptosis. The levels of superoxide dismutase (SOD) and catalase (CAT) were also markedly increased. Notably, the nanozymes downregulated senescence-associated secretory phenotype (SASP) factors, including IL-6, IL-1β, CXCL1, and TGF-β, indicating suppression of the proinflammatory senescent microenvironment. In vivo , Fe-curcumin nanozyme treatment effectively delayed cataract development in rats. Mechanistically, the nanozymes inhibited both senescence and apoptosis by modulating the p53/p21/BAX signaling axis, primarily through reducing p53 expression and phosphorylation levels. These findings suggest that Fe-curcumin nanozymes represent a promising therapeutic strategy for ARCs by suppressing oxidative damage, cellular senescence, and inflammation through targeting p53-related pathways.