Abstract
Retinal angiogenesis is a common neovascularization mechanism that causes severe irreversible vision loss in many retinal diseases worldwide. Patients often do not respond to the current anti-angiogenic therapies and have vision loss. Understanding the various angiogenic pathways and factors involved in the pathogenic mechanism is vital for disease management. In this study, we aim to identify dysregulated angiogenic pathways and specific angiogenic factors involved in vision-threatening retinal diseases namely proliferative diabetic retinopathy (PDR), retinopathy of prematurity (ROP) and neovascular age-related macular degeneration (nAMD). First, we identified the differentially expressed genes (DEGs) in all the retinal diseases and each disease compared to controls using microarray metadata. Subsequently, we performed Gene Set Enrichment analysis (GESA) for pathways, a protein-protein interaction (PPI), and angiome network analysis using R and Cytoscape software. We identified highly enriched dysregulated pathways that were neuroactive ligand receptor interaction and cytokine-cytokine receptor interaction. The angiogenic–associated DEGs were predominately related to the cytokine-cytokine receptor interaction pathway, which we further confirmed with RNA-seq data of PDR samples. Together, our analysis of these data elucidated the molecular mechanisms of retinal angiogenesis and provided potential angiogenic targets for therapeutics.
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