Identification and validation of druggable targets for cataract using mendelian randomization: functional insights from multi-omics and an oxidative stress model

Objective: To identify druggable genes associated with cataract and investigate their functional roles under oxidative stress, thereby providing potential therapeutic targets. Methods: , and cell viability, proliferation, apoptosis, and hub gene expression were assessed using CCK8, EdU, flow cytometry, and qPCR. Results: suppressed SRA01/04 cell viability and proliferation while promoting apoptosis in a dose-dependent manner. qPCR results showed that oxidative stress upregulated DKK3 and downregulated GSTM1 expression, both in a dose-dependent manner, consistent with MR findings, supporting DKK3 as a risk factor and GSTM1 as a protective factor for cataract. Conclusion: This study identified and validated DKK3 and GSTM1 as key genes in cataract pathogenesis. By integrating genetic analyses with functional experiments, our findings provide new insights into the molecular mechanisms of cataract and establish a theoretical basis for drug development and repurposing.