The Influence of Capsule Composition on Lens Biology

胶囊成分对晶状体生物学的影响

• 批准号: 8399302
• 负责人: MELINDA K DUNCAN
• 金额: $ 38.25万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8399302
• 关键词: Adverse effects; Basement membrane; Biology; Cataract; Cataract Extraction; Cell surface; Cells; Cicatrix; Communication; Data; Development; Embryo; Epithelial; Epithelial Cells; Epithelium; Excision; Extracapsular; Extracellular Matrix; Extracellular Matrix Proteins; Eye; Fibronectins; Gene Expression; Grant; Integrins; Investigation; Lens Fiber; Ligands; Mediating; Molecular; Molecular Target; Myofibroblast; Operative Surgical Procedures; Outcome; Pathogenesis; Pathway interactions; Patients; Phenotype; Play; Prevention; Process; Proteins; Regulation; Relative (related person); Role; Signal Pathway; Signal Transduction; Staging; Testing; Tissues; Vesicle; Visual; Work; base; capsule; cell behavior; epithelial to mesenchymal transition; fiber cell; insight; lens; lens capsule; prevent; transdifferentiation

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.

描述（由申请人提供）：晶状体囊是围绕晶状体的增厚基底膜，为晶状体细胞提供必要的结构支撑并介导晶状体与眼睛其余部分之间的连接。晶状体囊成分还充当附着的晶状体细胞的生存、增殖和分化信号，尽管晶状体囊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是未知的。整合素是介导细胞与其细胞外基质之间通讯的主要分子。在之前的资助周期中，我们发现各种整合素在晶状体发育以及后囊膜混浊（PCO）的发病机制中发挥着重要作用，PCO是白内障摘除手术的主要副作用。然而，整合素控制晶状体发育和 PCO 发病机制的机制尚不清楚。本申请旨在研究整合素控制命运决定的分子机制，从而调节晶状体上皮细胞的转变 发育过程中的纤维细胞和“珍珠型”PCO 以及纤维化 PCO 发育过程中上皮细胞和肌成纤维细胞之间的转变。这些研究包括对纤连蛋白（一种已知在 PCO 期间上调的整合素配体）在这种疾病发病机制中的分子功能的研究。 公共健康相关性：晶状体囊是一种尚未得到充分研究但至关重要的晶状体生物学调节因子。该应用旨在了解其在正常晶状体生物学调节和晶状体上皮细胞向肌成纤维细胞（疤痕组织的主要成分）的转化中发挥基本作用的分子机制。这项工作将为后白内障（后囊膜混浊）的发病机制提供基本见解，后白内障是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。