Rho GTPase signaling promotes constitutive expression and release of TGF-beta2 by human trabecular meshwork cells Journal Article

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Authors: Pervan, C. L.; Lautz, J. D.; Blitzer, A. L.; Langert, K. A.; Stubbs, E. B., Jr
Article Title: Rho GTPase signaling promotes constitutive expression and release of TGF-beta2 by human trabecular meshwork cells
Abstract: Elevated intraocular pressure (IOP) is causally implicated in the pathophysiology of primary open-angle glaucoma (POAG). The molecular mechanisms responsible for elevated IOP remain elusive, but may involve aberrant expression and signaling of transforming growth factor (TGF)-beta2 within the trabecular meshwork (TM). Consistent with previously published studies, we show here that exogenous addition of TGF-beta2 to cultured porcine anterior segments significantly attenuates outflow facility in a time-dependent manner. By comparison, perfusing segments with a TGFbetaRI/ALK-5 antagonist (SB-431542) unexpectedly elicited a significant and sustained increase in outflow facility, implicating a role for TM-localized constitutive expression and release of TGF-beta2. Consistent with this thesis, cultured primary or transformed (GTM3) quiescent human TM cells were found to constitutively express and secrete measurable amounts of biologically-active TGF-beta2. Disrupting monomeric GTPase post-translational prenylation and activation with lovastatin or GGTI-298 markedly reduced constitutive TGF-beta2 expression and release. Specifically, inhibiting the Rho subfamily of GTPases with C3 exoenzyme similarly reduced constitutive expression and secretion of TGF-beta2. These findings suggest that Rho GTPase signaling, in part, regulates constitutive expression and release of biologically-active TGF-beta2 from human TM cells. Localized constitutive expression and release of TGF-beta2 by TM cells may promote or exacerbate elevation of IOP in POAG.
Journal Title: Experimental eye research
Volume: 146
ISSN: 1096-0007; 0014-4835
Publisher: Unknown  
Date Published: 2015
Start Page: 95
End Page: 102
Language: ENG
DOI/URL:

S0014-4835(15)30095-6
Notes: LR: 20160411; CI: Published by Elsevier Ltd.; JID: 0370707; OTO: NOTNLM; 2015/08/05 [received]; 2015/12/15 [revised]; 2015/12/22 [accepted]; aheadofprint