Figure 17. Schematic diagrams depicting how impairment of Angpt-Tie2 signaling disintegrates the maintenance of SC integrity, leading to glaucomagenesis.
In normal adult SC, controlled Angpt–Tie2–ERK–Prox1 signaling cascade maintains appropriate AHO and intact GV. On the other hand, in glaucomatous or aged SC, inhibition of Angpt-Tie2 signaling attenuates ERK-Prox1 signaling and subsequently disrupts SC lumen, which consequently leads to decreased AHO. This, in turn, reduces transport of Angpt1 and Angpt2 through AH, resulting in further inhibition of the Angpt-Tie2 system in a vicious cycle manner. These exacerbating processes eventually trigger further disintegration of SC, inducing elevated IOP and accelerating POAG progression. Tie2 activation rejuvenates SC through upregulation of ERK-Prox1 signaling, which promotes AHO while decreasing IOP and eventually prevents POAG progression.