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Originally published In Press as doi:10.1167/iovs.09-3380 on August 20, 2009
 (Investigative Ophthalmology and Visual Science. 2010;51:308-318.)
© 2010 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.09-3380
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Ocular Gene Transfer of Active TGF-β Induces Changes in Anterior Segment Morphology and Elevated IOP in Rats

Jennifer V. Robertson,1 Elizabeth Golesic,1 Jack Gauldie,1,2 and Judith A. West-Mays1

From the 1Department of Pathology and Molecular Medicine and the 2Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada.

Corresponding author: Judith A. West-Mays, Department of Pathology and Molecular Medicine, McMaster University, HSC 1R10, Hamilton, ON L8B 3Z5, Canada; westmayj{at}mcmaster.ca.

Purpose. Transforming growth factor beta (TGF-β) is known to play a crucial role in wound healing and fibrotic tissue remodeling. A large body of evidence suggests a role for this cytokine in the pathogenesis of glaucoma; however, the mechanisms by which it affects anterior segment morphology are not well understood. Therefore, the purpose of this study was to examine the effects of TGF-β overexpression on anterior segment morphology and subsequent effects on intraocular pressure.

Methods. Adenoviral gene transfer was used to deliver active TGF-β1 to the rat eye. Measurements of intraocular pressure were taken with a tonometer on days 0, 14, 21, and 29. Histologic analysis was undertaken to examine anterior segment morphology, and markers of matrix deposition and fibrosis were used.

Results. Gene transfer of TGF-β in the anterior segment resulted in the formation of peripheral anterior synechiae (PAS), which consisted of a fibroproliferative region of corneal endothelial cells, matrix accumulation, and decrease in trabecular meshwork expression of {alpha}-smooth muscle actin. These features were accompanied by ocular hypertension.

Conclusions. Gene transfer of TGF-β into the anterior segment induces aberrant PAS associated with the transition of corneal endothelial cells and subsequent matrix deposition. These features are highly reminiscent of human iridocorneal endothelial (ICE) syndrome. Gene transfer of TGF-β can, therefore, be used to induce anatomic changes in the anterior segment in a rodent model that result in ocular hypertension.




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A. R. Shepard, J. C. Millar, I.-H. Pang, N. Jacobson, W.-H. Wang, and A. F. Clark
Adenoviral Gene Transfer of Active Human Transforming Growth Factor-{beta}2 Elevates Intraocular Pressure and Reduces Outflow Facility in Rodent Eyes
Invest. Ophthalmol. Vis. Sci., April 1, 2010; 51(4): 2067 - 2076.
[Abstract] [Full Text] [PDF]


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