Diagnostic Markers and Molecular Dysregulation Mechanisms in the Retinal Pigmented Epithelium and Retina of Age-Related Macular Degeneration

Abstract

Age-related macular degeneration (AMD) is a chronic and progressive macular degeneration disease, which can also lead to serious visual loss. In our research, we aim to efficiently identify biomarkers relevant for AMD diagnosis. We collected the gene expression data of retinal segmented epithelium (RPE) and retina tissues of GSE29801 and GSE135092 and performed differential expression analysis. The differentially expressed genes (DEGs) related to the RPE and retina in the two sets of data were identified and enriched by intersection analysis. A PPI network was constructed for intersection genes, and the top 20 genes with the largest connectivity in the network were selected as candidate genes. The LASSO model was used to identify key genes from candidate genes, and the nomogram and ROC curve were used to evaluate the diagnostic ability of key genes. We identified 464 intersection genes associated with RPE and 509 intersection genes associated with retina. The TGF-beta signaling pathway was enriched by RPE-related DEGs, while oxidative phosphorylation was enriched by retina-related DEGs. Among the candidate genes of RPE, the LASSO model identified 7 key genes. MAPK1 and LUM can predict the clinical diagnosis of AMD. Among the candidate genes of retina, the LASSO model identified four key genes. PTPN11 has the highest predictive diagnostic value. The results suggest that the imbalance mechanism of RPE in AMD may be related to the TGF-beta signaling pathway, and the imbalance mechanism of the retina may be related to oxidative phosphorylation. MAPK1 and LUM are potential diagnostic markers of RPE, and PTPN11 is a potential diagnostic marker of the retina. Also, our results provide a theoretical basis for better understanding the molecular mechanisms of AMD onset and treatment in the future.