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Unraveling the mechanisms underlying diabetic cataracts: insights from Mendelian randomization analysis
1College of Medical Technology, Xi'an Medical University, Xi'an, People's Republic of China.
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.
