IOP elevation significantly increased TBK1 expression and RGC senescence, but these could be mitigated by treatment with TBK1 shRNA, BX-795,22 or MK-2206.28 Notably, our findings provide a molecular link and pathway between TBK1 and p16, with TBK1 upregulation directly activating Akt Ser473 phosphorylation, Bmi1 Ser316 phosphorylation, p16 expression and RGC senescence in the pathogenesis of elevated IOP-induced retinal ischemia (Figure 9). This evidence concerns the gene BMI1 and retinal ischemia.