title: Ocular gene transfer of active TGF-beta induces changes in anterior segment morphology and elevated IOP in rats.
abstract: Purpose. Transforming growth factor beta (TGF-beta) 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-beta overexpression on anterior segment morphology and subsequent effects on intraocular pressure. Methods. Adenoviral gene transfer was used to deliver active TGF-beta1 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-beta 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-beta 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-beta can, therefore, be used to induce anatomic changes in the anterior segment in a rodent model that result in ocular hypertension.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jennifer V
authors.initials: JV
authors.lastname: Robertson
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Golesic
authors.forename: Jack
authors.initials: J
authors.lastname: Gauldie
authors.forename: Judith A
authors.initials: JA
authors.lastname: West-Mays
mesh_terms: D000199:Actins / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000869:Anterior Eye Segment / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D002386:Cataract / Q000209:etiology; D024141:Collagen Type IV / Q000378:metabolism; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression / Q000502:physiology; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D020287:In Situ Nick-End Labeling; D007429:Intraocular Pressure; D057129:Iridocorneal Endothelial Syndrome / Q000209:etiology / Q000473:pathology; D008297:Male; D008856:Microscopy, Fluorescence; D009798:Ocular Hypertension / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012164:Retinal Diseases / Q000209:etiology; D014065:Tonometry, Ocular; D014129:Trabecular Meshwork / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D000199:Actins; D015820:Cadherins; D024141:Collagen Type IV; D053773:Transforming Growth Factor beta1; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins