PIGMENT EPITHELIUM AND BRUCHS MEMBRANE

色素上皮和布鲁赫膜

• 批准号: 2019560
• 负责人: DAVID A NEWSOME
• 金额: $ 15.76万
• 依托单位: TOURO INFIRMARY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1998-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2019560
• 关键词: aging; antioxidants; catalase; chemoprevention; disease /disorder model; disease /disorder prevention /control; glycoproteins; human tissue; intermolecular interaction; laboratory rat; lipid peroxides; macular degeneration; malnutrition; metallothionein; model design /development; nutrition related tag; oxidative stress; phagocytosis; retinal pigment epithelium; tissue /cell culture; zinc

DESCRIPTION: (Adapted from applicant's abstract) The long-term objective of this proposal is a better understanding of fundamental biological processes in human eyes that play a role in protecting ocular tissues from the everyday exposure to potentially damaging reactive oxygen species. An inability to detoxify free radicals can lead to "wear and tear" and tissue damage such as that associated with aging and with age- related macular degeneration. Clinical investigations suggest that oral administration of antioxidants can retard vision loss from macular degeneration in at least some persons. Investigations at the cellular and molecular levels are proposed to learn more about chorioretinal antioxidant system elements, including zinc, catalase and metallothionein (MT) with the following specific aims: (1) to determine the interrelations of zinc, MT, and catalase in vitro and in vivo in providing the RPE protection from oxidative stress as reflected by changes in lipid peroxidation products; (2) to investigate the regulation of MT in the response of the RPE to the oxidative stress of ROS phagocytosis and exposure to increased reactive oxygen species; and (3) to determine the effects of zinc and oxidative stress on the formation of glycoconjugates by the RPE. Use will be made of isolated human donor RPE tissue, cultured human RPE cells, and an in vivo rat model of zinc deficiency. These studies will increase understanding of how molecules related to the antioxidant economy of RPE are regulated, and how they may affect other cellular functions, including the synthesis and degradation of Bruch's membrane. Understanding these basic cellular events is crucial to development of diagnostic and prognostic tools to treat the symptoms of macular degeneration.

描述：(改编自申请者摘要)长期目标 这一建议的核心是更好地理解基础生物学 人眼中起到保护眼组织作用的突起 从每天暴露在具有潜在破坏性的活性氧中 物种。不能解毒自由基会导致“磨损和 撕裂“和组织损伤，如与衰老和年龄相关的损伤- 相关性黄斑变性。临床研究表明，口服 服用抗氧化剂可以延缓黄斑部的视力丧失 至少在某些人中出现退化。在移动电话公司进行的调查 分子水平被认为是为了更多地了解脉络膜视网膜 抗氧化系统元素，包括锌、过氧化氢酶和 金属硫蛋白(MT)具有以下特定目的：(1)测定 锌、金属硫蛋白和过氧化氢酶在体内外的相互关系 提供RPE保护免受氧化应激的影响，这反映在 脂质过氧化产物的变化；(2)研究其调节 MT在RPE对ROS氧化应激反应中的作用 吞噬和暴露于增加的活性氧物种；和(3) 以确定锌和氧化应激对形成的影响 RPE对糖共轭化合物的影响。将使用隔离的人类捐赠者 RPE组织、培养的人RPE细胞和体内锌的大鼠模型 缺乏症。这些研究将增加对分子如何 与RPE的抗氧化剂经济性相关的是什么，以及它们是如何 可能会影响其他细胞功能，包括合成和 Bruch膜的降解。了解这些基本的细胞 Events对于开发诊断和预后工具至关重要 治疗黄斑变性的症状。