ICAM1 and Hyperglycemia: Hyperglycemia subsequently leads to vascular EC damage, and in turn, leukocyte aggregation/adhesion to vessel walls.216 Leukocyte adhesion and aggregation activate a massive amount of neutrophils that adhere to EC and form a reticular network and aggravate tissue hypoxia, causing vascular remodeling and neovascularization.217 The main protein that mediates intercellular adhesion is intercellular cell adhesion molecule-1 (ICAM-1).218 Under inflammation, ICAM-1 is abundantly expressed in retinal EC, where it binds to receptors.