REGULATION OF THE OUTER BLOOD-RETINAL BARRIER

外层血视网膜屏障的调节

• 批准号: 6070293
• 负责人: Steven D Wilt
• 金额: $ 3.03万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-10-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6070293
• 关键词: Rous sarcoma virus; animal tissue; cell cell interaction; chickens; chimeric proteins; disease vectors; gene expression; human tissue; membrane proteins; molecular site; mutant; protein binding; protein sequence; recombinant DNA; retina circulation; retinal pigment epithelium; rod cell; species difference; tight junctions; tissue /cell culture; transport proteins

The outer blood-retinal barrier is formed in part by the tight junctions of the retinal pigment epithelium (RPE). This blood- tissue barrier separates the photosensitive retina from the underlying vascular choriocapillaris. Maintenance of these tight junctions is vital to normal retinal physiology as observed in some retinopathies that result from a breakdown of this barrier. Tight junctions are composed of both transmembrane proteins and a submembranous complex of proteins known as the zonula occludens, or ZO, proteins. The ZO proteins belong to a larger class of proteins, the MAGUKs, that contain globular domains termed PDZ domain. Little is known about the function of the PDZ domain, although it has been suggested that they mediate interactions between the ZOs and may play a role in tight junction regulation. This proposal examines the role of ZO-2 subdomains in the regulation of RPE tight junctions using recombinant DNA techniques. A unique culture model (Ban and Rizzolo, 1997) that allows for different aspects of tight junction function to be assayed will be used to study the effect of gain-of-function and loss-of-function mutants in vitro.

视网膜外屏障部分由视网膜色素上皮（RPE）的紧密连接形成。 这种血液组织屏障将光敏的视网膜与下面的血管脉络膜毛细血管分开。 这些紧密连接的维持对正常的视网膜生理至关重要，如该屏障崩溃所致的一些视网膜病中所观察到的。紧密连接由跨膜蛋白和蛋白质蛋白质蛋白质蛋白质或ZO蛋白质组成。 ZO蛋白属于较大的蛋白质，即Maguks，其中包含称为PDZ结构域的球状域。 尽管有人提出它们介导ZOS之间的相互作用并可能在紧密的连接调节中起作用，但对PDZ域的功能知之甚少。该提案研究了使用重组DNA技术在RPE紧密连接的调节中的作用。 一个独特的培养模型（Ban and Rizzolo，1997）允许测定紧密连接函数的不同方面，将用于研究功能获得的功能和功能丧失突变体的体外效果。