KDR and endothelial dysfunction: Hyperglycemia-induced reactive oxygen species (ROS) abnormally phosphorylate VEGFR2 independently of VEGF-A,498 with elevated VEGFR2 expression in diabetic retinal microvascular ECs, especially in the macula.499 Consequently, VEGF-A phosphorylates tight junction proteins such as occludin, increasing permeability,500–502 and activates pathways such as phospholipase A2,503 PKC,504 and PI3K/AKT,505 driving endothelial dysfunction and plasma extravasation.