Abstract

Purpose This study aimed to investigate the potential link between age-related macular degeneration (AMD) and systemic lupus erythematosus (SLE), exploring whether AMD may share underlying autoimmune mechanisms with SLE. The objective was to identify shared core genes and potential diagnostic biomarkers for both diseases. Methods We utilized GEO datasets to develop diagnostic models and performed differential gene expression analysis, weighted gene co-expression network analysis (WGCNA), and three machine learning techniques—LASSO regression, random forest (RF), and support vector machine recursive feature elimination (SVM-RFE)—to identify common key genes between AMD and SLE. Mendelian randomization analysis was conducted to validate the potential causal relationship between AMD and the identified essential genes. Single-cell RNA sequencing data were analyzed to explore the expression patterns of shared biomarkers at the cellular level. The expression level of the identified biomarker was validated using reverse transcription quantitative polymerase chain reaction and Western blotting. Results Several shared core genes were identified as associated with both AMD and SLE. The Mendelian randomization study confirmed a potential correlation between AMD and these essential genes. Single-cell transcriptomic analysis revealed distinct expression profiles of these markers across relevant cell types, supporting their role in disease pathology. Conclusion Our findings suggest that AMD and SLE share key genetic features, supporting the hypothesis that AMD may have an autoimmune component. These shared genes hold promise as potential therapeutic targets and diagnostic biomarkers for both diseases.