Here, we review some of the commonly proposed degeneration pathways of RPE cells and their roles in the pathogenesis of AMD and DR, including activation of the complement cascade, oxidative stress-induced cell death mechanisms, dysfunctional mitochondria, chronic neuroinflammation mediated by microglial cells, and production of the vascular endothelial growth factor (VEGF) (Cheung et al., 2010; Barben et al., 2018; Massengill et al., 2018; Somasundaran et al., 2020). The gene discussed is VEGFA; the disease is age-related macular degeneration.