The Influence of Capsule Composition on Lens Biology

项目摘要 囊外白内障手术是现代医学的奇迹， 白内障相关失明的全球负担。然而，最佳植入a 替换眼内透镜需要保存大部分透镜囊、基底 围绕透镜的薄膜。由于透镜上皮细胞（LEC）紧密地附着在晶状体上皮细胞上， 透镜囊，在白内障手术中不可能去除所有的LEC，并且这些细胞 经历以细胞增殖为特征的稳健的伤口愈合反应， LEC转分化为瘢痕生成肌成纤维细胞。虽然现代眼内透镜 植入物可以隔离肌成纤维细胞远离眼轴短期，这些细胞可以 在囊袋的外围长期存活，并且经常在手术后数年逃逸， 迁移到视轴，在那里它们可以增殖，使囊膜起皱， 纤维化细胞外基质分子，导致后囊膜混浊的发生 (PCO)在初次白内障手术后数年。因此，了解 肌成纤维细胞长期存活并维持其表型是非常重要的。期间 在上一个格兰特周期，我们发现手术后透镜细胞产生的纤维连接蛋白是 对于纤维细胞去除后LEC的纤维化表型的维持至关重要。这 一项提案旨在研究纤连蛋白及其相互作用伙伴的机制， 介导透镜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.