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: 8091266
• 负责人: MELINDA K DUNCAN
• 金额: $ 41.55万
• 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 2012-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8091266
• 关键词: Affect; Animals; Anterior; Apoptosis; Aqueous Humor; Artificial Implants; Basement membrane; Binding; Biology; Cataract; Cell surface; Cells; Cellular biology; Cessation of life; Charge; Collagen; Collagen Type IV; Communication; Cornea; Crystalline Lens; Defect; Development; Diffusion; Disease; ECM receptor; Environment; Epithelial; Epithelial Cells; Epithelium; Excision; Extracellular Matrix Protein Gene; Eye; Fiber; Fluorescence Recovery After Photobleaching; Genes; Grant; Growth Factor; Hereditary nephritis; Homeostasis; Human; Integrins; Lens Fiber; Mediating; Molecular; Molecular Abnormality; Mus; Mutation; Nature; Pathology; Permeability; Phenotype; Play; Property; Proteins; Protocols documentation; Protomer; Role; Signal Transduction; Staging; Testing; Virus; Vision; Vitreous humor; aqueous; capsule; cell capsule; epithelial to mesenchymal transition; in vivo; lens; lens capsule; prevent; public health relevance; response

DESCRIPTION (provided by applicant): The lens capsule is a thickened basement membrane that completely surrounds the lens from its earliest developmental stages until death. It is well established that the lens capsule is crucial for lens development and function and lens capsule pathologies can threaten vision. An established function of the lens capsule is to serve as a selectable filter between the lens and the ocular environment, however, relatively little is known about the properties of this filter. During the prior grant cycle, we developed a robust fluorescence recovery after photobleaching (FRAP) protocol which can evaluate both the ability of molecules to enter the lens capsule and quantitatively determine their diffusion coefficient. In the first aim of this application, we propose to use FRAP to elucidate the molecular properties of the normal lens capsule filter. It is also known that mutations in extracellular matrix (ECM) protein genes result in cataract. The second aim tests the hypothesis that alterations in collagen IV activate the unfolded protein response leading to cataract. Another established function of the lens capsule is to engage ECM receptors on lens cells, providing both a structural anchor for the cell and inducing cell signaling cascades crucial for lens cell phenotype. Integrins are a major class of ECM receptors present on lens cells and ¿1 integrin is the major b-integrin subunit expressed by the lens. In the prior grant cycle, we created mice lacking ¿1 integrin in either all lens cells or just lens fibers to test the hypothesis that ¿1-integrin is important for lens cell/lens capsule communication. The phenotypes of the resulting animals are quite distinct and we now propose in specific aim three to elucidate the function of ¿1-integrin in the in vivo lens by analyzing the molecular abnormalities seen in these animals. Public Health Relevance: The lens capsule is important for the function of the normal ocular lens, although little is known about how diseases affecting the lens capsule result in lens abnormalities. Further, the lens capsule is usually retained in the eye after the surgical removal of cataracts to both support the implanted artificial replacement lens and to serve as a barrier, between the anterior and posterior portions of the eye, although the resulting abnormal lens cell/capsule interactions often result in secondary cataract. A complete understanding of the communication between lens cells and the capsule are crucial to develop treatments to prevent secondary cataract.

描述（由适用提供）：镜头胶囊是一种增厚的地下膜，从最早的发育阶段到死亡，完全围绕着镜头的环境。可以很好地确定，镜头胶囊对于晶状体开发和功能至关重要，镜头胶囊病理可能威胁到视力。镜头胶囊的建立功能是用作镜头和眼环境之间的可选滤波器，但是，对该滤镜的特性相对较少。在先前的赠款周期中，我们在光漂白（FRAP）方案后开发了可靠的荧光回收率，可以评估分子进入镜头胶囊的能力并定量确定其差异系数。在本应用的第一个目的中，我们建议使用FRAP阐明正常透镜胶囊滤波器的分子特性。还众所周知，细胞外基质（ECM）蛋白基因中的突变导致白内障。第二个目标检验了以下假设：胶原蛋白IV的改变激活了导致白内障的未折叠蛋白反应。镜头胶囊的另一个确定功能是在晶状体细胞上吸引ECM受体，为细胞提供结构锚，又为诱导的细胞信号传导级联而言对晶状体细胞表型至关重要。整联蛋白是存在于晶状体细胞上的主要ECM受体，1整联蛋白是晶状体表达的主要B-整合素亚基。在先前的赠款周期中，我们创建了在所有镜片细胞中缺乏1个整联蛋白的小鼠，或者仅仅是镜片纤维，以检验``1-整合素对镜片细胞/透镜胶囊通信都很重要的假设。所得动物的表型非常不同，我们现在在特定目标中提出，通过分析在这些动物中看到的分子异常，以阐明体内镜头中1-整合素的功能。公共卫生相关性：镜头胶囊对于正常眼镜的功能很重要，尽管对影响晶状体胶囊的疾病如何导致晶状体异常知之甚少。此外，手术去除白内障后，通常将透镜囊保留在眼睛中，以支撑植入的人造替换透镜，又支撑眼睛的前部和后部之间，尽管产生的异常透镜/胶囊相互作用通常会导致次级性省内核心。完全了解镜片细胞和胶囊之间的通信对于预防继发性白内障的发育处理至关重要。