Schematic illustration linking hyperglycemia-induced reactive oxygen species (ROS) overproduction with Ang-2–dependent vasoregression and combined ischemia/hypoxia-induced angiogenesis
Schematic illustration linking hyperglycemia-induced reactive oxygen species (ROS) overproduction with Ang-2–dependent vasoregression and combined ischemia/hypoxia-induced angiogenesis. In healthy retinal capillaries, proper pericyte coverage ensures endothelial cell survival and integrity of blood-retinal barrier by Ang-1/Tie-2 signaling. Chronic hyperglycemia induces cell damage and upregulation of Ang-2 in retinal endothelial cells and Müller cells (MC), leading to retinal pericyte detachment, migration, apoptosis, and progressive vasoregression. Occluded remnants of capillaries are no longer perfused, leading to the upregulation of survival/growth factors such as VEGF. During the later stages, which is not represented in rodent models, increased expression of hypoxia-induced VEGF and increased Ang-2 levels lead to preretinal neovascularization. HXP, hexosamine pathway; EC, endothelial cell. (A high-quality color representation of this figure is available in the online issue.)
