Unraveling the mechanisms underlying diabetic cataracts: insights from Mendelian randomization analysis.

Background: Diabetic cataract (DC) is a major cause of blindness, with its pathogenesis involving oxidative stress and ferroptosis, according to recent studies.

Methods: We performed a Mendelian Randomization (MR) study using GWAS data to select SNPs and assess the causal link between diabetes and cataracts. DC datasets were analyzed for differential gene expression, WGCNA, and protein-protein interactions to identify key oxidative stress and ferroptosis genes. An SVM-RFE algorithm developed a diagnostic model, and ImmuCellAI analyzed immune infiltration patterns.

Results: MR analysis confirmed diabetes as a cataract risk factor and identified core genes related to oxidative stress and ferroptosis in DC. Four key genes (Hspa5/Nfe2l2/Atf3/Stat3) linked to both processes were discovered. Immune infiltration analysis revealed an imbalance associated with these genes.

Conclusions: A functional interaction between oxidative stress and ferroptosis genes in DC is suggested, with a 4-gene model, indicating their potential as a 'bridge' in DC pathogenesis.