We found that acute IOP elevation-induced retinal ischemia directly increases TBK1 expression, triggering Akt S473 phosphorylation, activating Bmi1 phosphorylation, and upregulating the expression of p16, which leads to RGC senescence in cell culture and an IOP-induced retinal ischemia mouse model. Here, CDKN2A is linked to retinal ischemia.