Zhang Yuhang, Si Wei, Mao Yi, Xu Su, Li Fuzhen, Liu Jingjing, Du Shanshan, Shao Jingzhi, Qi Ying, Peng Xuyan, Xue Mengjiao, Jiang Mingjun, Guo Keyu, Hu Yanzhong, Zhang Fengyan
The Division of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
The Jointed National Laboratory of Antibody Engineering, Henan University, Kaifeng, China.
Commun Biol. 2025 Apr 15;8(1):613. doi: 10.1038/s42003-025-08067-y.
The Glucocorticoid-induced posterior subcapsular cataracts (GIC) is a common complication of patients received glucocorticoid treatment in clinic. We find that dexamethasone (DEX) induces lens epithelial cells' ferroptosis. DEX treatment increases intracellular ferroptosis signatures in lens epithelial cell line in vitro as well as in rat lens in vivo. The inhibition of ferroptosis by liproxstatin-1 reduces the incidence of DEX-induced rat GIC. Experimental evidence and expression profiling showed that DEX induces ferroptosis through upregulating tetraspanin CD82- controlled P53 expression. DEX-activated glucocorticoid receptors directly bind to the CD82 promoter, driving its transcriptional upregulation. CD82 expression is upregulated in the anterior capsular epithelium of GIC patients as well as in the DEX-treated rat lens and caused the cell death of anterior capsule. DEX treatment and Overexpression of CD82 in cells recapitulated ferroptotic signatures through P53 activation and GPX4/SLC7A11 suppression. Taken together, GIC is closely associated with the upregulation of CD82-P53-GPX4/SLC7A11 axis-mediated ferroptosis.
糖皮质激素诱导的后囊下白内障（GIC）是临床上接受糖皮质激素治疗的患者常见的并发症。我们发现地塞米松（DEX）可诱导晶状体上皮细胞发生铁死亡。DEX处理在体外的晶状体上皮细胞系以及体内的大鼠晶状体中均增加了细胞内铁死亡特征。liproxstatin-1对铁死亡的抑制降低了DEX诱导的大鼠GIC的发生率。实验证据和表达谱分析表明，DEX通过上调四跨膜蛋白CD82控制的P53表达来诱导铁死亡。DEX激活的糖皮质激素受体直接与CD82启动子结合，驱动其转录上调。GIC患者的前囊上皮以及DEX处理的大鼠晶状体中CD82表达上调，并导致前囊细胞死亡。DEX处理和细胞中CD82的过表达通过P53激活和GPX4/SLC7A11抑制重现了铁死亡特征。综上所述，GIC与CD82-P53-GPX4/SLC7A11轴介导的铁死亡上调密切相关。
