ROBO4 and Hyperglycemia: The present study have demonstrated that hyperglycemia-induced overexpression of TET2 can cause active demethylation of the ROBO4 promoter, increase ROBO4 expression by activating SP1 binding to the ROBO4 promoter, and decrease ZO-1 and occludin expression, which leads to retinal vascular leakage and neovascularization.