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）：镜头胶囊是透镜周围的地下膜增厚，可为晶状体细胞提供必不可少的结构支撑，并介导镜头和其余眼睛之间的连接。透镜胶囊成分还可以作为附着的晶状体细胞的生存，增殖和分化信号，尽管在晶状体囊中发现的每个细胞外基质蛋白对透镜细胞行为的相对贡献大多未表征。整合素是介导细胞与其细胞外基质之间的通信的主要分子。在先前的赠款周期中，我们发现各种整联蛋白在晶状体发育以及后囊膜无情中的发病机理（PCO）中起着重要作用，这是手术性白内障的主要副作用。但是，整合素控制晶状体发育和PCO发病机理的机制尚不清楚。该应用建议研究整联蛋白控制命运决策的分子机制，这些决策调节了晶状体上皮细胞的过渡 发育过程中的纤维细胞和“珍珠型” PCO以及在纤维化PCO发育过程中上皮细胞和成肌纤维细胞之间的过渡。这些研究包括对纤连蛋白的分子功能的研究，纤连蛋白是一种在PCO期间已知的整联蛋白配体，在这种情况的发病机理中。 公共卫生相关性：镜头胶囊是透镜生物学的研究研究的，但至关重要的调节剂。该应用旨在了解其在正常晶状体生物学的调节和晶状体上皮细胞向肌纤维细胞的转化（疤痕组织的主要成分）中的基本作用的分子机制。这项工作将提供有关伴抗后期乳酸（后囊状无情）发病机理的基本见解，这是白内障手术的主要副作用。这将使我们能够识别出其他分子靶标，以防止这种情况，从而为患者带来更好的最终视觉结果。