April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Effects of TGF-β2, BMPs-2/5/7, and Gremlin on Fibronectin in Human Trabecular Meshwork Cells
Author Affiliations & Notes
  • T. Tovar
    Cell Biology & Anatomy, University of North Texas Hlth Sci Ctr, Fort Worth, Texas
  • A. F. Clark
    Cell Biology & Anatomy, University of North Texas Hlth Sci Ctr, Fort Worth, Texas
  • R. J. Wordinger
    Cell Biology & Anatomy, University of North Texas Hlth Sci Ctr, Fort Worth, Texas
  • Footnotes
    Commercial Relationships  T. Tovar, None; A.F. Clark, None; R.J. Wordinger, None.
  • Footnotes
    Support  RO1 EY017374-01A1 (RJW)
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3209. doi:https://doi.org/
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      T. Tovar, A. F. Clark, R. J. Wordinger; Effects of TGF-β2, BMPs-2/5/7, and Gremlin on Fibronectin in Human Trabecular Meshwork Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3209. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Transforming growth factor beta 2 (TGF-β2) has been implicated in the development of elevated intraocular pressure in primary open-angle glaucoma (POAG). Glaucoma patients have increased levels of TGF-β2 in their aqueous humor, and TGF-β2 increases extracellular matrix (ECM) proteins such as fibronectin (FN) in trabecular meshwork (TM) cells. Bone morphogenetic protein 4 (BMP4) inhibits TGF-β2 induction of FN, which is reversed by the BMP antagonist gremlin. The purpose of the present study was to investigate whether other members of the BMP family, BMPs 2, 5, and 7 have the same antagonistic effect on TGF-β2 induction of fibronectin expression in human trabecular meshwork cells.

Methods: : Primary human TM cell strains were treated with TGF-β2 (5ng/ml), BMPs 2, 4, 5, or 7 (10ng/ml), gremlin (1ug/ml), or a combinations of TGF-β2, BMPs, and/or gremlin for 48 hours. The effects of TGF-β2, BMPs, and gremlin on FN expression were determined by western immunoblotting.

Results: : Exogenous TGF-β2 increased TM cell FN levels, and BMP-2, BMP-4 and BMP-7, but not BMP-5 blocked this fibronectin induction. The BMP antagonist gremlin blocked the negative effects of BMP-2, BMP-4 and BMP-7 and enhanced FN expression.

Conclusions: : TGF-β2 induction of ECM (e.g. fibronectin) deposition may be responsible for the elevated intraocular pressure in POAG. The human trabecular meshwork modulates TGF-β2 effects on the ECM with BMPs. However, this modulatory effect is opposed by gremlin, which blocks the negative action of BMP-2, BMP-4 and BMP-7 and leads to increased expression of ECM. The pharmacological modulation of gremlin may provide a novel therapeutic target in glaucoma.

Keywords: growth factors/growth factor receptors • trabecular meshwork • intraocular pressure 
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