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: 6718550
• 负责人: MELINDA K DUNCAN
• 金额: $ 22.65万
• 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 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6718550
• 关键词: animal genetic material tag; basement membrane; cell adhesion; cell differentiation; cell growth regulation; cell migration; cell proliferation; collagen; gene expression; genetically modified animals; histogenesis; human fetus tissue; integrins; laboratory mouse; lens; phenotype; protein structure function

DESCRIPTION (provided by applicant): The lens capsule is an acellular, thickened basement membrane that completely surrounds the lens from its earliest developmental stages until death. Numerous studies have shown that the capsule is essential for lens development and function and a number of human and animal diseases result in lens capsule abnormalities, often leading to the degradation or destruction of vision. Recently, we demonstrated that the composition of the collagen IV network changes during lens development so that the collagen IV subtypes associated with basement membrane elasticity are expressed during early development while those associated with basement membrane strength are not expressed until after eye lid opening. This led to the hypothesis that the expression of lens capsule components changes during development to allow for both the 200 fold increase in capsule area during embryogenesis and the strength necessary for accomodation. This hypothesis will be tested by changing the collagen IV subtype composition of the lens using transgenic mouse approaches. Since at least one class of basement membrane molecules is differentially synthesized during lens development, we hypothesize that other basement membrane molecules will have similar expression profiles which could also have dramatic consequences on lens function. Thus, the developmental expression pattern of extracellular matrix molecules found to be expressed in the lens by our prior microarray analyses will be determined as well. The role that both the changing collagen IV subtype composition and the presence of other extracellular matrix molecules in the lens capsule plays in lens biology will be tested by cell adhesion, migration and proliferation assays on either primary cultures of mouse lens epithelial cells or freshly isolated bovine lens epithelial cells in the presence or absence of matrix components. These studies will both elucidate the molecular composition of the lens capsule and address the role that the capsule plays in the biology of the attached lens cells.

描述（由申请人提供）：镜头胶囊是一种细胞增厚的地下膜，从最早的发育阶段到死亡，完全围绕着镜头。许多研究表明，胶囊对于晶状体的发展和功能至关重要，许多人类和动物疾病会导致镜头胶囊异常，通常导致视力降解或破坏。最近，我们证明了镜头发育过程中胶原蛋白IV网络的变化的组成，因此在早期发育过程中表达了与基底膜弹性相关的胶原蛋白IV亚型，而与基底膜强度相关的胶原蛋白亚型直到眼镜张开后才表达与基底膜强度相关的胶原蛋白。这导致了以下假设：透镜胶囊成分在发育过程中的变化，以使胚胎发生过程中囊区域的200倍增加和住宿所必需的强度。该假设将通过使用转基因小鼠方法更改镜头的胶原蛋白IV亚型组成来检验。由于在晶状体发育过程中至少合成了至少一类地下膜分子，因此我们假设其他地下膜分子将具有相似的表达谱，这也可能对镜片功能产生巨大的后果。因此，还将确定通过我们先前的微阵列分析在镜头中表达的细胞外基质分子的发育表达模式。在晶状体生物学中，镜头胶囊中的其他细胞外基质分子的存在以及其他细胞外基质分子的存在的作用将通过细胞粘附，迁移和增殖测定在小鼠晶状体细胞上的一级培养物上，或新鲜分离的牛角细胞或新鲜分离的Bovine镜头细胞的作用。这些研究都将阐明透镜胶囊的分子组成，并解决胶囊在附着的晶状体细胞生物学中的作用。