circ_EPB41 Modulates the miR-15a-5p/Bcl-2 Pathway to Alleviate Oxidative Stress Damage in Lens Epithelial Cells.

PURPOSE: This study aimed to investigate the role of circ_EPB41 in regulating oxidative stress-induced apoptosis in lens epithelial cells by targeting the miR-15a-5p/Bcl-2 pathway, highlighting its potential significance in age-related cataract treatment. Growing evidence suggests that circular RNAs and microRNAs play critical roles in age-related cataract development, making circ_EPB41 a promising target.

METHODS: SRA01/04 cells were exposed to 200 µM H2O2 for 24 h to induce oxidative damage and model age-related cataract. Cell viability and apoptosis were assessed using MTT assays and flow cytometry, respectively. The interaction between circ_EPB41 and miR-15a-5p was analyzed through bioinformatics tools and dual luciferase reporter assays. Additionally, the expression levels of Bax, Bcl-2, miR-15a-5p, and circ_EPB41 were measured using RT-qPCR and Western blot analysis.

RESULTS: H2O2-induced SRA01/04 cells showed down-regulation of circ_EPB41 and up-regulation of miR-15a-5p. Circ_EPB41 was found to interact with miR-15a-5p, negatively regulating its expression. Furthermore, miR-15a-5p mimics reversed the effects of circ_EPB41 on oxidative stress in SRA01/04 cells, as evidenced by reduced cell viability, increased apoptosis, elevated Bax levels, and decreased Bcl-2 expression. In contrast, miR-15a-5p inhibitors alleviated H2O2-induced oxidative damage by upregulating Bcl-2 expression.

CONCLUSION: This study is the first to demonstrate that up-regulation of circ_EPB41 protects lens epithelial cells from oxidative stress-induced apoptosis through the miR-15a-5p/Bcl-2 pathway. These findings suggest that circ_EPB41 may hold potential as a novel therapeutic target for age-related cataract treatment.