USP10 inhibits the apoptosis of lens epithelial cells and delays the progression of diabetic cataract via the deubiquitination and stabilization of MCL1

As one of the complications of diabetes mellitus (DM), diabetic cataract (DC) has become the critical cause of vision impairment. MCL1 is an antiapoptotic protein in the BCL2 family that plays an important role in cell survival and proliferation. The role of MCL1 in DC remains unclear. Exploring the function of MCL1 and its underlying regulatory mechanism in DC can provide new prevention ideas. Here, high-glucose (HG)-cultured lens epithelial cells (LECs) and streptozotocin (STZ)-induced diabetic model rats were used. MTT assays, western blotting, immunohistochemical (IHC) assays and propidium iodide (PI) staining were utilized to analyse LECs apoptosis. Immunofluorescence staining was used to assess ROS levels in LECs in a high-glucose environment. Overexpression experiments and co-IP analyses were performed to assess the protein‒protein interaction between MCL1 and USP10. The results showed that HG induced apoptosis and oxidative stress in LECs and induced cataract in diabetic rats. MCL1 overexpression inhibited HG-induced apoptosis. Moreover, USP10 stabilized the MCL1 protein by binding to and deubiquitinating MCL1, and this binding was attenuated in HG environments. Furthermore, the antioxidant (-)-Epigallocatechin-3-gallate (EGCG) significantly delayed cataract progression in diabetic rats by reversing oxidative stress-induced LECs apoptosis in a HG environment. In summary, our experiments revealed that USP10 inhibited LECs apoptosis and the occurrence of DC in a HG environment by deubiquitination and stabilization of MCL1. The antioxidant EGCG significantly delayed cataract progression in diabetic rats by reversing oxidative stress-induced LECs apoptosis in a HG environment. Our study helps elucidate the molecular mechanism of DC and provides new therapeutic targets and ideas for the subsequent development of nonsurgical treatment options.