A Systems Biology Approach to miRNA–mRNA Regulatory Networks in Age-Related Macular Degeneration: Network Topology and Pathway Enrichment

Abstract

Purpose: The study aimed to explore the role of microRNA (miRNA)–messenger RNA (mRNA) interactions in age-related macular degeneration (AMD) using a systems biology framework. Methods: A comprehensive literature review was conducted to curate experimentally validated miRNA–mRNA interactions related to AMD. A bipartite interaction network was constructed and analyzed using network topology measures, including degree and betweenness centrality, to identify key regulators. Community detection was performed using the Louvain algorithm, and functional enrichment analysis of target genes was conducted using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases with multiple-testing correction. Results: The network comprised 125 nodes and 100 edges. VEGFA, BCL2, SIRT1, and IL6 emerged as hub genes, while VEGFA and STAT3 were key bottlenecks. Community detection revealed five modules enriched in functionally coherent genes. GO analysis highlighted inflammation, angiogenesis, oxidative stress, apoptosis, and extracellular matrix regulation. KEGG analysis identified VEGF, PI3K-Akt, NF-κB, TGF-β, and complement signaling pathways. Conclusions: The findings provide systems-level insight into coordinated post-transcriptional regulation in AMD and support the potential of miRNAs as biomarkers and multi-target therapeutic candidates.