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(Investigative Ophthalmology and Visual Science. 2007;48:715-726.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-0226
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Bone Morphogenetic Protein-7 Is an Antagonist of Transforming Growth Factor-ß2 in Human Trabecular Meshwork Cells

Rudolf Fuchshofer,1 Alice H. L. Yu,2 Ulrich Welge-Lüssen,2 and Ernst R. Tamm1

1From the Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany; and the 2Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany.

PURPOSE. The increase in intraocular pressure in primary open-angle glaucoma (POAG) may involve transforming growth factor (TGF)-ß2 signaling, as TGF-ß2 is found in higher amounts than normal in the aqueous humor of patients with POAG. In vitro, TGF-ß2 causes an accumulation of extracellular matrix (ECM) in the trabecular meshwork (TM) and an increase in TM outflow resistance. The present study was undertaken to determine whether bone morphogenetic protein (BMP)-7 signaling antagonizes the effects of TGF-ß2 on TM cells.

METHODS. Cultured TM cells from nine human donors were treated with BMP-7, TGF-ß2, or a combination of both for 24 or 72 hours. The expression of connective tissue growth factor (CTGF); thrombospondin (TSP)-1; fibronectin; collagen types I, III, and IV; plasminogen activator inhibitor (PAI)-1; and matrix metalloproteinase (MMP)-2 were analyzed by immunohistochemistry, real time RT-PCR, Western and Northern blot analysis, and zymography (MMP-2).

RESULTS. Treatment with TGF-ß2 induced the expression of CTGF, TSP-1, fibronectin, collagen types IV and VI, and PAI-1. All these effects were inhibited when TGF-ß2 was added in combination with BMP-7, whereas BMP-7 alone had no effects. Treatment with TGF-ß2, BMP-7, or the combination of both had no effect on the expression of collagen types I and III.

CONCLUSIONS. BMP-7 strongly antagonizes in vitro the TGF-ß-induced expression of a broad panel of molecules, which would result in an accumulation of TM ECM in situ. As BMP-7 is expressed in the adult human TM in situ, it seems reasonable to assume that it similarly modulates and antagonizes the effects of TGF-ß2 signaling on the tissues of the outflow pathways in vivo. The pharmacological modulation of BMP-7 signaling in the TM might be a promising strategy to treat POAG.




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