Smad-independent TGF-β2 signaling pathways in human trabecular meshwork cells

Aberrant expression and signaling of Transforming Growth Factor (TGF)-beta is strongly associated with development of elevated intraocular pressure (IOP) and primary open-angle glaucoma (POAG). In cells of the trabecular meshwork, a key component of the conventional outflow pathway, TGF-beta is well-known to promote expression of multiple ocular hypertensive mediators, including genes associated with fibrosis as well as cellular contractility. These effects are mediated by induction of canonical (Smad) as well as non-canonical (MAPK, Rho GTPase) signaling cascades. In the present review, we will highlight the non-canonical, Smad-independent signaling pathways activated by TGF-beta 2 in human TM cells, as well as the genes known to be induced by non-canonical TGF-beta 2 signaling. Published by Elsevier Ltd.