The Influence of Capsule Composition on Lens Biology

项目摘要 白内障囊外手术是现代医学的一个奇迹，它大大减少了 全球白内障相关失明的负担。然而，最佳植入 人工晶状体置换术需要保留大部分晶状体囊、基底膜 晶状体周围的薄膜。由于晶状体上皮细胞(LECs)紧密地附着在 晶状体囊，在白内障手术中不可能去除所有的晶状体上皮细胞，而这些细胞 经历强大的伤口愈合反应，其特征是细胞增殖和 晶状体上皮细胞转分化为瘢痕形成肌成纤维细胞。而现代人工晶状体 植入物可以在短期内将肌成纤维细胞隔离在眼轴之外，这些细胞可以 在囊袋的外围长期存活，手术后经常逃脱数年， 迁移到视轴，在那里它们可以增殖，使囊膜起皱，并产生 纤维性细胞外基质分子导致后囊混浊 (PCO)在最初的白内障手术后数年。因此，了解通过什么机制 肌成纤维细胞长期存活并保持其表型具有重要意义。在.期间 在上一个资助周期，我们发现手术后晶状体细胞产生的纤维连接蛋白是 在去除纤维细胞后维持晶状体上皮细胞的纤维化表型至关重要。这 一项提案旨在调查纤维连接蛋白及其相互作用伙伴 介导晶状体上皮细胞的纤维化表型。

Project Summary Extracapsular cataract surgery is a marvel of modern medicine that has greatly reduced the global burden of cataract-related blindness. However, optimal implantation of a replacement intraocular lens requires preservation of most of the lens capsule, the basement membrane surrounding the lens. Since lens epithelial cells (LECs) are tightly attached to the lens capsule, it is not possible to remove all LECs during cataract surgery, and these cells undergo robust wound healing responses characterized by cell proliferation and the transdifferentiation of LECs to scar producing myofibroblasts. While modern intraocular lens implants can sequester myofibroblasts away from the ocular axis short term, these cells can survive long term at the periphery of the capsular bag, and often escape years after surgery, migrating into the visual axis, where they can proliferate, wrinkle the capsule, and produce fibrotic extracellular matrix molecules, leading to the onset of posterior capsular opacification (PCO) years after the initial cataract surgery. Thus, understanding the mechanisms by which myofibroblasts survive and maintain their phenotype long term is of great importance. During the last grant cycle, we discovered that fibronectin produced by lens cells after surgery was critical for the maintenance of the fibrotic phenotype of LECs post fiber cell removal. This proposal seeks to investigate the mechanisms by which fibronectin and its interacting partners mediate the fibrotic phenotype of lens epithelial cells.