PIGMENT EPITHELIUM AND BRUCHS MEMBRANE

色素上皮和布鲁赫膜

• 批准号: 2634385
• 负责人: DAVID A NEWSOME
• 金额: $ 16.39万
• 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/2634385
• 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：（改编自申请人摘要）长期目标 这一建议的一个更好的理解是基本的生物学 在保护眼组织中起作用的人眼过程 从每天暴露在潜在的有害活性氧中 物种无法清除自由基会导致“磨损和 撕裂”和组织损伤，例如与老化和年龄相关的损伤， 黄斑变性临床研究表明，口服 抗氧化剂的管理可以延缓视力丧失从黄斑 至少在某些人中是如此。在蜂窝调查 和分子水平，建议了解更多关于脉络膜视网膜 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）确定 锌，MT和过氧化氢酶在体外和体内的相互关系， 提供RPE免受氧化应激的保护， 脂质过氧化产物的变化;（2）探讨其调控机制 MT在RPE对ROS氧化应激反应中的作用 吞噬作用和暴露于增加的活性氧;和（3） 以确定锌和氧化应激对形成的影响， 糖复合物的形成。将使用分离的人类供体 RPE组织、培养的人RPE细胞和锌的体内大鼠模型 缺陷这些研究将增加对分子如何 与RPE的抗氧化经济性有关的调节，以及它们如何 可能影响其他细胞功能，包括合成和 Bruch膜的降解。了解这些基本的细胞 事件对于开发诊断和预后工具至关重要， 治疗黄斑变性的症状。

项目成果

Altered synthesis of Bruch's membrane proteoglycans associated with dominant retinitis pigmentosa.

布鲁赫膜蛋白聚糖的合成改变与显性色素性视网膜炎相关。

• DOI: 10.3109/02713688509000846
• 发表时间: 1985
• 期刊: Current eye research
• 影响因子: 2
• 作者: Hewitt,AT;Newsome,DA
• 通讯作者: Newsome,DA

Analysis of newly synthesized Bruch's membrane proteoglycans.

• 发表时间: 1989-03
• 期刊: Investigative ophthalmology & visual science
• 影响因子: 4.4
• 作者: A. Hewitt;K. Nakazawa;D. A. Newsome

Altered proteoglycans in cultured human retinitis pigmentosa retinal pigment epithelium.

培养的人视网膜色素变性视网膜色素上皮中蛋白聚糖的改变。

• 发表时间: 1988
• 期刊: Investigative ophthalmology & visual science
• 影响因子: 4.4
• 作者: Hewitt,AT;Newsome,DA
• 通讯作者: Newsome,DA

Altered glycoconjugates in cultures of retinitis pigmentosa retinal pigment epithelium.

视网膜色素变性视网膜色素上皮培养物中糖缀合物的改变。

• 发表时间: 1987
• 期刊: Progress in clinical and biological research
• 作者: Hewitt,AT;Newsome,DA
• 通讯作者: Newsome,DA

Normal vascular development in mice deficient in endothelial NO synthase: possible role of neuronal NO synthase.

• 发表时间: 2003-10
• 期刊: Molecular vision
• 影响因子: 2.2
• 作者: M. Al-Shabrawey;A. El-Remessy;X. Gu;Steven S. Brooks;M. S. Hamed;Paul L Huang;R. Caldwell