The Influence of Capsule Composition on Lens Biology

描述(申请人提供)：晶状体囊膜是包围晶状体的一层增厚的基底膜，它为晶状体细胞提供必要的结构支撑，并调节晶状体和眼睛剩余部分之间的连接。晶状体囊膜成分也是晶状体细胞存活、增殖和分化的信号，尽管晶状体囊膜中发现的每种细胞外基质蛋白对晶状体细胞行为的相对贡献大多尚未确定。整合素是调节细胞与细胞外基质之间通讯的主要分子。在之前的资助周期中，我们发现各种整合素在晶状体发育以及后囊混浊(PCO)的发病机制中发挥着重要作用，PCO是手术摘除白内障的主要副作用。然而，整合素控制晶状体发育的机制和后囊混浊的发病机制尚不清楚。这项应用旨在研究整合素控制调节晶状体上皮细胞转变的命运决定的分子机制 在纤维化的PCO发展过程中，上皮细胞和肌成纤维细胞之间的过渡。这些研究包括对纤维连接蛋白的分子功能的研究，纤维连接蛋白是一种已知的在PCO过程中上调的整合素配体，在这种情况下的发病机制。 与公共健康相关：晶状体囊膜是晶状体生物学中一个未被充分研究但却至关重要的调节因子。这项应用旨在了解其在调节正常晶状体生物学和将晶状体上皮细胞转化为瘢痕组织的主要成分肌成纤维细胞中的基本作用的分子机制。这项工作将为后发性白内障(后囊混浊)的发病机制提供基本的见解，后囊膜混浊是白内障手术的主要副作用。这将使我们能够确定更多的分子靶点来预防这种情况，这可能会为患者带来更好的最终视觉结果。

DESCRIPTION (provided by applicant): The lens capsule is a thickened basement membrane surrounding the lens which provides essential structural support for lens cells and mediates connection between the lens and the remainder of the eye. Lens capsule components also serve as survival, proliferation and differentiation signals for the attached lens cells although te relative contribution of each extracellular matrix protein found in the lens capsule to lens cell behavior is mostly uncharacterized. Integrins are major molecules mediating the communication between cells and their extracellular matrix. During the prior grant cycle we discovered that various integrins play essential roles in lens development as well as the pathogenesis of posterior capsular opacification (PCO), the major side effect of surgical cataract removal. However, the mechanisms by which integrins control lens development and the pathogenesis of PCO is not well understood. This application proposes to investigate the molecular mechanisms by which integrins control the fate decisions which regulate transitions from lens epithelial cells to fiber cells during development and "pearl type" PCO as well as transitions between epithelial cells and myofibroblasts during the process of fibrotic PCO development. These studies include investigations into the molecular function of fibronectin, an integrin ligand known to upregulate during PCO, in the pathogenesis of this condition. PUBLIC HEALTH RELEVANCE: The lens capsule is an understudied, but crucial regulator of lens biology. This application seeks to understand the molecular mechanisms underlying its fundamental role in both the regulation of normal lens biology and the conversion of lens epithelial cells to myofibroblasts, a main component of scar tissue. This work will provide fundamental insights into the pathogenesis of after-cataract (posterior capsular opacification), the major side effect of cataract surgery. This will allow us to identify additional molecular targets to prevent this condition which could result in better final visual outcomes for patients.