The Influence of Capsule Composition on Lens Biology

描述（由申请人提供）：透镜囊是围绕透镜的增厚基底膜，为透镜细胞提供必要的结构支撑，并介导透镜和眼睛其余部分之间的连接。透镜囊组分还充当附着的透镜细胞的存活、增殖和分化信号，尽管在透镜囊中发现的每种细胞外基质蛋白对透镜细胞行为的相对贡献大多未被表征。整合素是介导细胞与其细胞外基质之间通讯的主要分子。在之前的研究周期中，我们发现各种整合素在透镜发育以及后囊混浊（PCO）的发病机制中起着重要作用，PCO是白内障手术切除的主要副作用。然而，整合素控制透镜发育和PCO发病机制的机制还不清楚。本申请提出研究整联蛋白控制命运决定的分子机制，所述命运决定调节从透镜上皮细胞的转变 在纤维化PCO的发生过程中，上皮细胞向肌成纤维细胞的转变以及“珍珠型”PCO。这些研究包括纤连蛋白的分子功能的调查，一种整合素配体，已知在PCO过程中上调，在这种情况下的发病机制。 公共卫生相关性：透镜囊是一种未充分研究的，但却是透镜生物学的关键调节器。本申请寻求理解其在正常透镜生物学的调节和透镜上皮细胞向肌成纤维细胞（瘢痕组织的主要成分）的转化中的基本作用的分子机制。这项工作将提供基本的见解，后发性白内障（后囊混浊）的发病机制，白内障手术的主要副作用。这将使我们能够确定额外的分子靶点来预防这种情况，从而为患者带来更好的最终视力结果。

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.