VEGFA and Hyperglycemia: Advanced glycation end-products promote NF-kB activation by interacting with the cellular RAGEs on the cell surface.234 This leads to retinal pericyte apoptosis and elevated expression of VEGF, inflammatory cytokines, and adhesion molecules.235 Inhibition of ACEs can improve hyperglycemia-induced blood-retinal barrier leakage and reduce retinal EC proliferation, migration, and neovascularization,236 thus alleviating DR.