Targeting YAP/TAZ mechanosignaling to ameliorate stiffness-induced Schlemm’s canal cell pathobiology
Haiyan Li, Megan Kuhn, Ruth A. Kelly, Ayushi Singh, Kavipriya Kovai Palanivel, Izzy Salama, Michael L. De Ieso, W. Daniel Stamer, Preethi S. Ganapathy, Samuel Herberg
Abstract
Pathologically altered biomechanical properties of the Schlemm's canal (SC) inner wall microenvironment were recently validated as the cause for increased outflow resistance in ocular hypertensive glaucoma. However, the involvement of specific mechanotransduction pathways in these disease processes is largely unclear. Here, we demonstrate that Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) are central regulators of glaucoma-like SC cell dysfunction in response to extracellular matrix stiffening and that targeted disruption of YAP/TAZ mechanosignaling attenuates SC cell pathobiology and enhances outflow function.