Trelford Charles B, Denstedt James T, Armstrong James J, Hutnik Cindy M L
Schulich School of Medicine and Dentistry, Department of Physiology and Pharmacology, Western University, London, Ontario, Canada.
Schulich School of Medicine and Dentistry, Department of Ophthalmology, Western University, London, Ontario, Canada.
Clin Ophthalmol. 2020 May 22;14:1391-1402. doi: 10.2147/OPTH.S245915. eCollection 2020.
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.
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.
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.
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.
本研究旨在比较从接受青光眼药物治疗的患者（青光眼患者）和未接受青光眼治疗的患者（非青光眼患者）获取的人眼球筋膜囊成纤维细胞（HTCFs）在伤口愈合和纤维化方面的差异。
使用原代HTCF接种的胶原晶格生成生物人工组织（BATs）。在BAT培养后，比较青光眼患者和非青光眼患者HTCFs中的促纤维化基因表达。还分别使用α-平滑肌肌动蛋白免疫组织化学、苦味酸天狼星红染色和胶原收缩试验对BATs的成纤维细胞-肌成纤维细胞转化、胶原重塑和胶原收缩进行评估。
与非青光眼患者相比，来自青光眼患者的BAT培养的HTCFs中的促纤维化基因表达显著增加。与从非青光眼患者分离的HTCFs相比，植入从青光眼患者收集的HTCFs的BATs表现出更大比例的肌成纤维细胞以及增加的胶原收缩/重塑。
青光眼患者和非青光眼患者的HTCFs在参与纤维化的基因表达、经历转分化为肌成纤维细胞的成纤维细胞比例、收缩特性和胶原重塑方面存在差异。这些结果表明，由于多种原因，在细胞水平上，接受青光眼药物治疗的患者的眼睛易于发生纤维化。
