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: 6983392
• 负责人: MELINDA K DUNCAN
• 金额: $ 22.12万
• 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 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6983392
• 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）：晶状体囊是一种无细胞的增厚基底膜，从晶状体最早的发育阶段直至死亡，它完全包围着晶状体。大量研究表明，晶状体囊对于晶状体的发育和功能至关重要，许多人类和动物疾病会导致晶状体囊异常，通常导致视力下降或破坏。最近，我们证明了 IV 型胶原蛋白网络的组成在晶状体发育过程中发生变化，因此与基底膜弹性相关的 IV 型胶原蛋白亚型在早期发育过程中表达，而与基底膜强度相关的亚型直到眼睑张开后才表达。这导致了这样的假设：晶状体囊成分的表达在发育过程中发生变化，使得胚胎发生期间囊面积增加了 200 倍，并且适应所需的强度也增加了 200 倍。该假设将通过使用转基因小鼠方法改变晶状体的 IV 型胶原蛋白亚型组成来进行测试。由于至少一类基底膜分子在晶状体发育过程中合成有差异，因此我们假设其他基底膜分子将具有相似的表达谱，这也可能对晶状体功能产生巨大影响。因此，我们之前的微阵列分析发现在晶状体中表达的细胞外基质分子的发育表达模式也将被确定。 IV 型胶原蛋白亚型组成的变化和晶状体囊中其他细胞外基质分子的存在在晶状体生物学中所起的作用将通过对小鼠晶状体上皮细胞或新鲜分离的牛的原代培养物进行细胞粘附、迁移和增殖测定来测试存在或不存在基质成分的晶状体上皮细胞。这些研究将阐明晶状体囊的分子组成，并解决晶状体囊在附着的晶状体细胞的生物学中所发挥的作用。