Piezo1 Activates an Autocrine Angiopoietin-2-Integrin Signaling Loop in Schlemm's Canal to Regulate Intraocular Pressure.

ABSTRACT: Intraocular pressure (IOP) is the most important risk factor in glaucoma pathogenesis. IOP is regulated by segmental, flow-dependent responses of the inner-wall endothelium of Schlemm's canal (SC), and dysfunction of this system contributes to ocular hypertension and glaucoma. Here, we identify a cell-autonomous PIEZO1-ANGPT2-integrin α9 (ITGA9)-focal adhesion kinase (FAK) mechanotransduction pathway that enables SC endothelial cells to respond to pressure and flow stimuli to maintain IOP homeostasis. Pharmacological activation of the mechanosensitive ion channel PIEZO1 with Yoda1 enhanced ITGA9 accumulation at cell-cell junctions in vitro and induced FAK phosphorylation in an ITGA9- and ANGPT2-dependent manner. In vivo in SC, PIEZO1 activation reduced intracellular ANGPT2, increased junct

SUBMITTER: Kiyota N 

PROVIDER: S-EPMC12633313 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature