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P. K. Russ, A. Kupperman, S.-H. Presley, F. R. Haselton, M. Chang; Bves Regulates Tight Junction Formation and RhoA Signaling in TM Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4883.
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© ARVO (1962-2015); The Authors (2016-present)
Blood Vessel Epicardial Substance (Bves) is novel adhesion molecule that regulates tight junction (TJ) formation. In addition to their role in cell-cell adhesion, TJs also modulate RhoA signaling, which has been implicated in outflow regulation. Since Bves has been reported in multiple ocular tissues, we hypothesize that Bves plays a role in regulation of RhoA signaling in TM cells.
TM cell lines from non-glaucomatous donors (NTM-5) and NTM-5 cells transfected to over-express Bves (NTM-w) were evaluated for TJ formation. Levels of TJ occludin and ZO-1 message and protein were compared. Functional assays for TJs were carried out using diffusion of sodium fluorescein in a two-chamber assay and transcellular electrical resistance. Levels of activated Rho were detected using FRET probes, and phosphorylated myosin light chain (MLC-p), a downstream target of RhoA, was assessed by Western blot.
Overexpression of Bves leads to increased TJ formation in NTM-5 cells. Increased TJ formation was confirmed by increased occludin message and protein. Functionally, NTM-w cells showed decreased permeability and increased transcellular electrical resistance compared to NTM-5 cells, consistent with increased TJ formation. NTM-w cells also exhibited decreased levels of active RhoA and lower levels of MLC-p compared to NTM-5 cells. These findings are in agreement with the role of TJs in RhoA signaling.
Increased Bves in TM cells leads to increased TJ formation with decreased RhoA activation and decreased MLC-p. In TM tissue, RhoA has been implicated in outflow regulation. This is the first report of a regulatory pathway upstream of RhoA in TM cells, and thus Bves potentially serves as a key regulatory molecule in aqueous outflow.
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