Ocular Gene Transfer of Active TGF Induces Changes in Anterior Segment Morphology and Elevated IOP in Rats

¹ Pathology/Molec. Medicine, McMaster University, Hamilton, Canada

^* To whom correspondence should be addressed. E-mail: robertjv{at}mcmaster.ca.

	Abstract

Purpose: Transforming growth factor beta (TGF) 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 over-expression on anterior segment morphology and subsequent effects on intraocular pressure. Methods: Adenoviral gene transfer was used to deliver active TGF1 to the rat eye. Measurements of intraocular pressure were taken with the Tono-Pen® XL on days 0, 14, 21 and 29. Histological analysis was undertaken to examine anterior segment morphology and markers of matrix deposition and fibrosis were utilized. Results: Gene transfer of TGF in the anterior segment resulted in 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 -smooth muscle actin. These features were accompanied by ocular hypertension. Conclusions: Gene transfer of TGF into the anterior segment induces aberrant PAS associated with transition of corneal endothelial cells and subsequent matrix deposition. These features are highly reminiscent of human iridocorneal endothelial (ICE) syndrome. Gene transfer of TGF can therefore be used to induce anatomical changes in the anterior segment of in a rodent model that result in ocular hypertension.

Key Words: corneal endothelial cells, intraocular pressure, gene transfer, glaucoma