Abstract
PURPOSE: Diabetic retinopathy (DR) is a significant complication of diabetes, with complex pathogenesis involving epigenetic modifications. This study aimed to explore the epigenetic regulatory mechanisms contributing to DR. METHODS: DR-related data, including DNA methylation, mRNA, and miRNA expression datasets, were obtained from the Gene Expression Omnibus database. Differential gene expression analysis was performed to identify differentially methylated genes and expressed mRNAs and miRNAs. Cross-analysis established the methylation-expression and miRNA-mRNA regulatory networks. A comprehensive DR-related epigenetic regulatory network was constructed, identifying hub genes. The expression characteristics of these hub genes in various immune cells were examined using single-cell RNA sequencing. RESULTS: We identified 10,716 differentially methylated genes, 1,181 differentially expressed mRNAs, and 615 differentially expressed miRNAs in DR. The methylation-expression regulatory network was associated with pathways such as TGF-beta and ErbB signaling. The miRNA regulatory network was linked to pathways related to cellular senescence, adherents junctions, and endocytosis. Five hub genes were identified: TFRC, AP2M1, AP2A1, DAB2, and PPP1CB. Single-cell RNA sequencing revealed specific expression of these genes in particular immune cells, highlighting their potential roles in DR pathogenesis. CONCLUSION: This study constructed a comprehensive epigenetic regulatory network for DR and identified key regulatory genes, offering new insights into the molecular mechanisms underlying DR and potential therapeutic targets for diagnosis and treatment.