Proteomics of altered protein in macular degeneration

黄斑变性中蛋白质改变的蛋白质组学

• 批准号: 6992685
• 负责人: Deborah Ann Ferrington
• 金额: $ 14.5万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6992685
• 关键词: aldehydes; gene expression; human old age (65+); human tissue; immunoprecipitation; macular degeneration; matrix assisted laser desorption ionization; molecular pathology; oxidative stress; proteomics; retina; retinal pigment epithelium; two dimensional gel electrophoresis

DESCRIPTION (provided by applicant): Currently, there is no preventative treatment for age-related macular degeneration (AMD), the leading cause of blindness among the elderly in the U.S.. Development of therapeutic interventions will require an understanding of the molecular events associated with the disease. In this proposal, we will test the hypothesis that a subset of proteins will be uniquely altered with AMD and that the progression of AMD will involve an evolution of protein changes that are manifest in clinically distinct features. This research will take an innovative analytical approach by using proteomic technology to identify specific proteins that are altered in the sensory retina and retinal pigment epithelium (RPE) with AMD. Donors selected (ages 65-75) will include those exhibiting either no AMD (control) or retinal features that are indicative of the beginning or later stages of the disease. The following aims will be pursued: (1) Evaluate and classify retinal degeneration in donor eyes. Prior to biochemical analysis, we will evaluate the macular region of donor eyes using the Age-related Eye Disease (AREDS) system. (2) Identify alterations in retinal proteins using proteomic analysis. We will perform proteome analysis to identify proteins in the RPE and sensory retina that have altered expression or contain the oxidative modification, 4-hydroxynonenal. Using donor retinas at clinically defined stages of AMD should aid in distinguishing patterns of protein changes that are associated with the progression of the disease. Identification of proteins that are uniquely altered will help provide valuable insight into the mechanism of AMD.

描述（由申请人提供）：目前，还没有针对年龄相关性黄斑变性（AMD）的预防性治疗方法，AMD 是美国老年人失明的主要原因。治疗干预措施的开发需要了解与年龄相关性黄斑变性相关的分子事件。这种疾病。 在本提案中，我们将测试以下假设：AMD 会独特地改变一部分蛋白质，并且 AMD 的进展将涉及临床上独特特征中表现出来的蛋白质变化的演变。这项研究将采用创新的分析方法，利用蛋白质组学技术来识别 AMD 导致感觉视网膜和视网膜色素上皮 (RPE) 发生改变的特定蛋白质。选定的捐赠者（65-75 岁）将包括那些没有表现出 AMD（对照）或表明疾病处于早期或晚期阶段的视网膜特征的捐赠者。我们将追求以下目标：（1）对供体眼睛的视网膜变性进行评估和分类。在生化分析之前，我们将使用年龄相关眼病 (AREDS) 系统评估供体眼睛的黄斑区域。 (2) 使用蛋白质组分析识别视网膜蛋白质的改变。我们将进行蛋白质组分析，以鉴定 RPE 和感觉视网膜中表达发生改变或含有氧化修饰 4-羟基壬烯醛的蛋白质。在 AMD 的临床定义阶段使用供体视网膜应有助于区分与疾病进展相关的蛋白质变化模式。鉴定出独特改变的蛋白质将有助于深入了解 AMD 的机制。