Proteomics of altered protein in macular degeneration

描述(申请人提供)：目前，美国没有针对老年性黄斑变性(AMD)的预防性治疗，AMD是导致老年人失明的主要原因。治疗干预措施的发展将需要了解与疾病相关的分子事件。在这个提案中，我们将检验这样的假设，即AMD的一部分蛋白质子集将被独特地改变，并且AMD的进展将涉及在临床上明显特征的蛋白质变化的进化。这项研究将采用一种创新的分析方法，使用蛋白质组学技术来识别AMD患者视网膜和视网膜色素上皮(RPE)中改变的特定蛋白质。选择的捐献者(年龄65-75岁)将包括那些没有AMD(对照)或视网膜特征的人，这些特征表明疾病的开始或后期。本研究的目的如下：(1)对供眼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)系统评估供眼的黄斑区域。(2)用蛋白质组学分析鉴定视网膜蛋白质的变化。我们将进行蛋白质组分析，以确定RPE和感觉性视网膜中表达发生变化或含有氧化修饰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该有助于区分与疾病进展相关的蛋白质变化模式。识别独特改变的蛋白质有助于为AMD的发病机制提供有价值的见解。

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.