Understanding the Molecular Basis of Pathological Retinal Angiogenesis: Roles of Lipids, Non-Coding RNAs, and Cellular Crosstalk

Pathological retinal neovascularization is a prevalent cause of blindness, impacting millions of individuals across all age groups, from infants to older adults. It is a key clinical feature of several retinal diseases, such as diabetic retinopathy (DR), retinopathy of prematurity (ROP), age-related macular degeneration (AMD), and Coats disease. Researchers have extensively investigated the involvement of vascular endothelial growth factor (VEGF) signaling, hypoxia inducible factor (HIF) signaling, and inflammation in the regulation of pathological retinal neovascularization. Recent breakthroughs have demonstrated the influence of several substances and cells in the retina on the regulation of pathological retinal neovascularization. This review emphasizes the rising significance of substances such as lipid mediators, non-coding ribonucleic acids, as well as the involvement of several retinal cell types, including endothelial cells (ECs), pericytes, glial cells, and the retinal pigment epithelium (RPE) in the regulation of pathological neovascularization. Here, we emphasize the interactions among these cell types in maintaining retinal homeostasis and their role in abnormal neovascularization in diseases like DR, AMD, ROP, etc. This review aims to highlight the importance of molecules and cells that go beyond the VEGF-centric therapeutic focus to treat pathological neovascularization.