TNFα and SOCS3 regulate IRS-1 to increase retinal endothelial cell apoptosis

► High glucose increases TNFα and SOCS levels in retinal endothelial cells. ► Knockdown of TNFα and SOCS3 reduces pro-apoptotic protein levels. ► TNFα inhibits insulin signaling through increased phosphorylation on IRS-1Ser307 in hyperglycemia. ► SOCS3 inhibits insulin signaling through decreased total IRS-1 levels and increased IRTyr960 binding in hyperglycemia.