Identification of Immune-related Core Genes Based on Immune Signatures of Age-related Macular Degeneration

Abstract

Abstract Background Age-related macular degeneration (AMD) is a disease that affects the retina and choroid and is the leading cause of blindness in older adults. Despite the prevalence of this disease, its etiology and pathogenesis are unknown, and many studies have shown that the immune system plays an important role in the development and progression of age-related macular degeneration. Here, we aimed to explore the immune profile of different stages of age-related retinopathy and to identify immune-related biomarkers that could improve the treatment of patients with age-related retinopathy. Methods Publicly available gene expression profiles of AMD samples at different stages of the disease were downloaded from the GEO database (GSE115828 dataset). The activity of 19 immune signatures in AMD retinal samples was assessed using ssGSEA, and the changes in immune levels at different stages of AMD were compared. Differential expression analysis was performed on advanced AMD samples, and the screened immune-related differentially expressed genes (DEGs) were used as a candidate gene set. We constructed an AMD-related model based on AMD immune-related DEGs by logistic regression and least absolute shrinkage and selection operator (LASSO), which was also verified by ROC curve. Finally, protein-protein interaction (PPI) networks were mapped using STRING and further analyzed using Cytoscape software. Results As AMD progresses to advanced stages, the activity of 13 immune signatures gradually increases. A total of 91 immune-related DEGs were identified by differential expression analysis and further submitted to LASSO regression model for screening, and a total of 12 core genes were identified (AUC = 0.827). Three important clusters with a high degree of intermolecular interactions were identified in the PPI network, revealing three major molecular mechanisms, including MHC class II antigen processing and presentation, microglia activation and complement activation. Conclusion Multiple immune signatures play an important role in the development of age-related macular degeneration. Twelve core immune-related genes were identified that warrant investigation in experimental and clinical studies. PPI network analysis revealed three immune-related molecular mechanisms of AMD.