Lens epithelial cells (LECs) apoptosis induced by oxidative stress is a major factor in age-related-cataract (ARC) pathogenesis, but there are still many blind nodes in this progress. This study aimed to investigate the effects of MDM2 phosphorylation in ARC and H₂O₂-induced lens epithelial cells apoptosis. Our results confirmed that the levels of p-MDM2 (Ser166) and p-MDM2 (Ser186) in the anterior lens capsules of human cataracts were reduced compared to that in normal capsules. Similarly, in naturally aging cataract mice, the level of MDM2 phosphorylation also decreased. Oxidative stress-induced apoptosis model was constructed by cultivating HLE-B3 cells with 200 μM H₂O₂. It was confirmed that MDM2 could regulate lens epithelial cell apoptosis, and MDM2 inhibitors could partly inhibited AKT’s role in suppressing apoptosis induced by H₂O₂. Besides, we examed the decreased level of p-AKT(Ser473) in apoptosis of lens epithelial cells and ARC. Our study revealed that MDM2 phosphorylation mediated H₂O₂-induced lens epithelial cells apoptosis and ARC, which could provide new ideas for the clinical treatment of ARC.

氧化应激诱导的晶状体上皮细胞（LECs）凋亡是年龄相关性白内障（ARC）发病机理的主要因素，但是在这一进展中仍然存在许多盲点。本研究旨在探讨MDM2磷酸化在ARC和H ₂ O ₂诱导的晶状体上皮细胞凋亡中的作用。我们的结果证实，与正常胶囊相比，人白内障前镜囊中p-MDM2（Ser166）和p-MDM2（Ser186）的水平降低。同样，在自然衰老的白内障小鼠中，MDM2磷酸化水平也降低了。通过用200μMH ₂ O ₂培养HLE-B3细胞来构建氧化应激诱导的凋亡模型。证实了MDM2可以调节晶状体上皮细胞凋亡，并且MDM2抑制剂可以部分抑制AKT在抑制H ₂ O ₂诱导的凋亡中的作用。此外，我们检查了晶状体上皮细胞和ARC的凋亡中p-AKT（Ser473）水平的降低。我们的研究表明，MDM2磷酸化介导的H ₂ O ₂诱导晶状体上皮细胞凋亡和ARC，这可能为ARC的临床治疗提供新的思路。