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，与年龄相关的黄斑变性（AMD）尚无预防治疗，这是美国老年人在美国老年人中失明的主要原因。治疗干预措施的发展将需要了解与该疾病相关的分子事件。 在此提案中，我们将检验以下假设：蛋白质的子集将随着AMD的形式唯一改变，并且AMD的进展将涉及蛋白质变化的演变，这些变化在临床上不同的特征中表现出来。这项研究将通过使用蛋白质组学技术来鉴定具有AMD的感觉视网膜和视网膜色素上皮（RPE）改变的特定蛋白质，采用创新的分析方法。选定的捐助者（65-75岁）将包括那些表现为NO AMD（对照）或视网膜特征的捐助者，这些特征表明该疾病的开始或更晚阶段。将追求以下目标：（1）评估和分类供体眼中的视网膜变性。在进行生化分析之前，我们将使用与年龄相关的眼病（AREDS）系统评估供体眼的黄斑区域。 （2）使用蛋白质组学分析确定视网膜蛋白质的改变。我们将进行蛋白质组分析，以鉴定RPE和感觉视网膜中改变表达或包含氧化修饰的4-羟基诺烯烯的蛋白质。在临床定​​义的AMD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。识别被唯一改变的蛋白质将有助于提供对AMD机制的宝贵见解。