Yongshun Liang,1 Qingqiao Gan,1 Xin Zhong,1 Tian Lan,1 Yingqin Yang,2 Lixia Lin,1 Chengye Tang,1 Hao Liang1 

1Department of Ophthalmology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of Ophthalmology, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, People’s Republic of China

Correspondence: Hao Liang, Department of Ophthalmology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, QingxiuDistrict, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China, Email liangh@stu.gxmu.edu.cn

Background: To determine the effect of senescence marker protein 30 (SMP30) regulation on the levels of p-STAT3 in the pathophysiology of lens epithelial cells (LECs) pyroptosis in cataracts.
Methods: Initially, cataracts were induced in rats using ultraviolet B (UVB) irradiation. Transmission electron microscopy was utilized to observe morphological changes in rat LECs, and RT-qPCR was utilized to quantify SMP30 and pyroptosis-related marker genes (GSDMD, Caspase-1, NLRP3, IL-1β, and IL-18). Subsequently, SMP30-AAV2 vectors were injected into the vitreous cavity to overexpress SMP30 in rat lenses. Proteomic analysis identified differential proteins associated with pyroptosis post-SMP30 overexpression. Stable SMP30-overexpressing human LECs (SRA01/04 cells) were established via lentiviral transfection. Western blot, ELISA, and RT-qPCR were used to investigate the role of SMP30 in the pyroptosis of LECs treated with H2O2. Additionally, rescue experiments with p-STAT3 agonists and inhibitors elucidated SMP30’s molecular mechanisms in H2O2-induced LECs pyroptosis.
Results: After UVB irradiation, SMP30 expression significantly decreased in rat lens capsules, while pyroptosis-related marker gene expression markedly increased. Ten crucial pyroptosis-related proteins were identified by proteomic analysis following SMP30 overexpression, with STAT3 receiving the highest score. SMP30 overexpression during H2O2-induced pyroptosis in SRA01/04 cells significantly decreased the expression of pyroptosis-related markers (GSDMD, Caspase-1, NLRP3, IL-1β, and IL-18). The p-STAT3 agonist Colivelin weakened the anti-pyroptotic effect of SMP30, while the p-STAT3 inhibitor Stattic enhanced the anti-pyroptotic effect of SMP30.
Conclusion: The expression levels of SMP30 were downregulated in cataract cell pyroptosis. When overexpressed, SMP30 can reduce lens epithelial cell pyroptosis by downregulating the expression of p-STAT3. Thus, SMP30 demonstrates promising potential in preventing and treating cataracts.

Keywords: pyroptosis, SMP30, p-STAT3, cataract, lens epithelial cells