Rajendran Vijayalakshmi, Netuková Magdalena, Griffith May, Forrester John V, Kuffová Lucia
Section of Immunity, Infection and Inflammation, University of Aberdeen, Aberdeen, Scotland, United Kingdom.
Department of Ophthalmology, Vinohrady Teaching Hospital, Charles University, Prague, Czech Republic.
Acta Biomater. 2017 Dec;64:346-356. doi: 10.1016/j.actbio.2017.10.011. Epub 2017 Oct 10.
Artificial corneas (keratoprostheses) and biosynthetic collagen-based corneal equivalents are surgical implants designed to ease the global burden of corneal blindness. However, keratoprostheses in many cases fail due to development of fibrous retro-corneal membranes (RCM). Fibrous membranes which develop in the anterior chamber after prosthesis implantation do so on a matrix of fibrin. This study investigated fibrin deposition and RCM formation after full-thickness collagen-based hydrogel implants and compared them with syngeneic and allogeneic corneal grafts in mice. Fibrin cleared from the anterior chamber within 14 days in both allo- and syn-grafts but, persisted in hydrogel implants and developed into dense retro-corneal membrane (RCM) which were heavily infiltrated by activated myofibroblasts. In contrast, the number of CD11b macrophages infiltrating the initial deposition of fibrin in the anterior chamber (AC) after hydrogel implantation was markedly reduced compared to syn- and allo-grafts. Inoculation of mesenchymal stem cells prior to collagen gel implant promoted clearance of gel-associated fibrin from the anterior chamber. We propose that a failure of macrophage-mediated clearance of fibrin may be the cause of RCM formation after collagen-based hydrogel implants and that mesenchymal stem cell therapy promotes clearance of fibrin and prevents RCM formation.
The manuscript addresses the potential value of bone marrow-derived mesenchymal stem cell therapy for retro-corneal membrane (RCM) formation in full-thickness transplantation of biosynthetic corneal equivalents. This work reports the pathophysiological changes in the anterior chamber of the mouse eye following full-thickness recombinant human cross-linked collagen-based hydrogel implants in which persistent fibrin promotes the development of dense RCM. Furthermore, pre-treatment with mesenchymal stem cells reduces RCM formation and enhances corneal transparency.
人工角膜（角膜假体）和基于生物合成胶原蛋白的角膜替代物是旨在减轻全球角膜盲负担的外科植入物。然而，在许多情况下，角膜假体由于纤维性角膜后膜（RCM）的形成而失败。假体植入后在前房形成的纤维膜是在纤维蛋白基质上形成的。本研究调查了全层胶原蛋白基水凝胶植入后纤维蛋白沉积和RCM形成情况，并将其与小鼠的同基因和异基因角膜移植进行比较。在同种异体和同基因移植中，纤维蛋白在前房内14天内清除，但在水凝胶植入物中持续存在并发展成致密的角膜后膜（RCM），被活化的肌成纤维细胞大量浸润。相比之下，与同种异体和同基因移植相比，水凝胶植入后浸润前房（AC）中纤维蛋白初始沉积的CD11b巨噬细胞数量明显减少。在胶原蛋白凝胶植入前接种间充质干细胞可促进前房内与凝胶相关的纤维蛋白清除。我们认为，巨噬细胞介导的纤维蛋白清除失败可能是基于胶原蛋白的水凝胶植入后RCM形成的原因，间充质干细胞疗法可促进纤维蛋白清除并防止RCM形成。
该手稿探讨了骨髓来源的间充质干细胞疗法在生物合成角膜替代物全层移植中对角膜后膜（RCM）形成的潜在价值。这项工作报告了在全层重组人交联胶原蛋白基水凝胶植入后小鼠眼前房的病理生理变化，其中持续存在的纤维蛋白促进了致密RCM的发展。此外，间充质干细胞预处理可减少RCM形成并提高角膜透明度。
