The Pro-Fibrotic Behavior of Human Tenon’s Capsule Fibroblasts in Medically Treated Glaucoma Patients

Abstract

Charles B Trelford,1 James T Denstedt,2 James J Armstrong,2,3 Cindy ML Hutnik2–4 1Schulich School of Medicine and Dentistry, Department of Physiology and Pharmacology, Western University, London, Ontario, Canada; 2Schulich School of Medicine and Dentistry, Department of Ophthalmology, Western University, London, Ontario, Canada; 3Schulich School of Medicine and Dentistry, Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada; 4Ivey Eye Institute, St. Joseph’s Healthcare, London, Ontario, CanadaCorrespondence: Charles B Trelford N6A 3K7 Tel [phone]Email [email protected]: The aim of this study was to compare human Tenon’s capsule fibroblasts (HTCFs) obtained from patients who received medical therapy for glaucoma (glaucomatous patients) and patients not treated for glaucoma (non-glaucomatous patients) in terms of wound healing and fibrosis.Patients and Methods: Bioartificial tissues (BATs) were generated using primary HTCF-populated collagen lattices. Pro-fibrotic gene expression within HTCFs was compared between glaucomatous patients and non-glaucomatous patients after BAT culture. The BATs were also assessed regarding fibroblast–myofibroblast transition, collagen remodeling and collagen contraction using alpha-smooth muscle actin immunohistochemistry, picrosirius red staining and collagen contraction assays, respectively.Results: Pro-fibrotic gene expression in BAT-cultured HTCFs derived from glaucomatous patients was significantly increased compared to non-glaucomatous patients. BATs imbued with HTCFs collected from glaucomatous patients exhibited a greater proportion of myofibroblasts as well as increased collagen contraction/remodeling compared to HTCFs isolated from non-glaucomatous patients.Conclusion: HTCFs from glaucomatous and non-glaucomatous patients differ in the expression of genes involved in fibrosis, proportion of fibroblasts undergoing transdifferentiation into myofibroblasts, contractile properties and collagen remodeling. These results suggest that for any number of reasons, at a cellular level, patients who received medical therapy for glaucoma have eyes primed for fibrosis.Keywords: fibrosis, tenon’s capsule, bioartificial tissue, glaucoma, human Tenon’s capsule fibroblasts

Keywords

• fibrosis tenon’s capsule bioartificial tissue glaucoma human tenon’s capsule fibroblasts