EDN1 and open-angle glaucoma: There are several indications that elevated IOP mechanically strains TM cells (e.g, via stretching ECM), which perturbs Ca2+ homeostasis and restructures the architecture of the ECM/cytoskeleton: (a) mechanical stress increases [Ca2+]TM11 and triggers the formation of actin stress fibers12; (b) [Ca2+]TM is elevated in eyes with primary open angle glaucoma (POAG) compared to control eyes13; and (c) agents that elevate [Ca2+]TM (endothelin-1, bradykinin) increase the TM resistance to aqueous outflow9, whereas actin depolymerizers increase the conventional ‘outflow facility’ and lower IOP10, 14.