Gao Xiang, Li Kewei, Huang Yan, Long Ziyan, Xiang Yongguo, Zheng Wendi, Cheng Hong, Cao Huijie, Wan Wenjuan, Zheng Shijie, Wang Xianwen, Hu Ke
The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Prevention and Treatment on Major Blinding Diseases, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of the National Clinical Research Center for Ocular Diseases, Chongqing, 400016, PR China.
School of Biomedical Engineering, Anhui Medical University, Hefei, 230032, PR China.
Mater Today Bio. 2025 May 8;32:101850. doi: 10.1016/j.mtbio.2025.101850. eCollection 2025 Jun.
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. experiments revealed that Fe-curcumin nanozymes significantly reduced reactive oxygen species (ROS) levels in HO-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. , 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.
年龄相关性白内障（ARCs）是全球视力损害的主要原因，主要由晶状体上皮细胞（LECs）中氧化应激诱导的衰老和凋亡引起。在本研究中，使用亚硒酸钠诱导的新生大鼠氧化应激白内障模型来模拟ARCs的病理过程。我们研究了铁-姜黄素纳米酶通过靶向细胞衰老和氧化损伤来延缓ARCs进展的治疗潜力。实验表明，铁-姜黄素纳米酶显著降低了过氧化氢（HO）处理的LECs中的活性氧（ROS）水平，减轻了细胞衰老，并减少了细胞凋亡。超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的水平也显著升高。值得注意的是，纳米酶下调了衰老相关分泌表型（SASP）因子，包括白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、CXC趋化因子配体-1（CXCL1）和转化生长因子-β（TGF-β），表明抑制了促炎衰老微环境。因此，铁-姜黄素纳米酶治疗有效地延缓了大鼠白内障的发展。机制上，纳米酶通过调节p53/p21/BAX信号轴抑制衰老和凋亡，主要是通过降低p53的表达和磷酸化水平。这些发现表明，铁-姜黄素纳米酶通过靶向p53相关途径抑制氧化损伤、细胞衰老和炎症，代表了一种有前途的ARCs治疗策略。
