Biomarkers for Age-Related Macular Degeneration

年龄相关性黄斑变性的生物标志物

• 批准号: 8321969
• 负责人: JOHN W CRABB
• 金额: $ 19.63万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8321969
• 关键词: Advanced Glycosylation End Products; Affect; Age; Age related macular degeneration; Antioxidants; Autoantibodies; Biological Assay; Biological Markers; Biology; Blindness; Bruch' s basal membrane structure; Choroid; Clinical; Clinical Medicine; Complement; Development; Diagnosis; Disease; Docosahexaenoate; Drusen; Elderly; Environment; Enzyme-Linked Immunosorbent Assay; Epidemic; Exhibits; Future; Genetic Polymorphism; Genomics; Genotype; Goals; Immune response; Individual; Inflammation; Inflammatory; Link; Lipids; Measurement; Medicine; Modification; Monitor; Mus; N(6)-carboxymethyllysine; Natural Immunity; Ophthalmologist; Ophthalmology; Oxidative Stress; Patient Care; Patients; Phenotype; Plasma; Plasma Proteins; Population; Population Study; Post-Translational Protein Processing; Predisposition; Prevalence; Process; Proteins; Proteomics; Publishing; Reactive Oxygen Species; Reporting; Research; Resources; Risk; Risk Marker; Smoking; Susceptibility Gene; Technology; Testing; Therapeutic; Tissues; Toll-Like Receptor 2; Treatment Efficacy; Vitamins; adduct; advanced disease; angiogenesis; base; complement system; experience; geographic atrophy; glycation; in vivo; macula; mouse model; neovascularization; pentosidine; prevent; prognostic; repository; sugar; tool; vision science

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. In the USA the prevalence of advanced AMD is approaching epidemic proportions. The long-term goal of the proposed research is the development of prognostic technology for use in clinical medicine to assess AMD risk for severe visual loss and to monitor the efficacy of AMD therapeutics. We have quantified plasma CEP (carboxyethylpyrrole) biomarkers and genotyped four AMD risk polymorphisms in over 1400 AMD and control subjects. The AMD risk for those exhibiting elevated CEP markers and AMD risk genotypes was 2-3 fold greater than the risk based on genotype alone. Preliminary published results from a relatively small study population suggest that plasma protein carboxymethyllysine (CML) and pentosidine exhibit AMD biomarker potential. Namely, CML and CEP adducts discriminate between AMD and control subjects with about equal accuracy (~78%), pentosidine with ~88% accuracy, and CEP plus pentosidine with ~92% accuracy. Unpublished preliminary results also indicate that CEP biomarkers have potential utility in monitoring select AMD therapeutics and that CML and pentosidine offer promise in assessing the risk of progression to advanced dry AMD. We hypothesize that plasma protein CEP, CML and pentosidine in combination with genomic markers will provide clinically useful prognostic tests for assessing the risk of severe visual loss due to AMD and for monitoring AMD therapeutics. Two specific aims are proposed: (1) Validate plasma protein CML and pentosidine as AMD biomarkers in a larger study population in combination with genomic markers of AMD risk; and (2) Develop a LC MS/MS assay for plasma protein CEP adducts to enhance the accuracy, precision and utility of CEP measurements as predictors of AMD risk. Unique resources supporting the proposed research include our large repository of plasma from clinically documented, extensively characterized AMD and control donors, our state-of-the-art proteomic, mass spectrometric and genomic technologies, over a decade of experience in AMD biology and a world-class clinical ophthalmology and basic vision science research environment. )

与年龄相关的黄斑变性（AMD）是全球失明的主要原因。在美国 晚期AMD的患病率正在接近流行比例。拟议的长期目标 研究是用于用于评估AMD风险的临床医学预后技术的开发 严重的视觉损失并监测AMD治疗剂的功效。我们已经量化了血浆CEP （羧乙基吡咯）生物标志物和基因分型在超过1400 AMD和对照中的四个AMD风险多态性 主题。表现出升高CEP标记和AMD风险基因型的AMD风险为2-3倍 仅基于基因型的风险大。初步发布的研究结果相对较小 人口表明血浆蛋白羧甲基氰（CML）和戊糖苷表现出AMD生物标志物 潜在的。也就是说，CML和CEP加合物区分AMD和控制受试者 精度（〜78％），精度约为88％的五丝氨酸，CEP和五托氨酸的精度约为92％。 未发表的初步结果还表明，CEP生物标志物在监视选择方面具有潜在的效用 AMD治疗剂以及CML和戊糖苷在评估发展的风险方面有望 晚期干amd。我们假设血浆蛋白CEP，CML和戊糖苷与 基因组标记将提供临床上有用的预后测试 进行AMD和监测AMD治疗剂。提出了两个具体目的：（1）验证血浆蛋白 在较大的研究人群中，CML和戊糖苷是AMD生物标志物，结合基因组标记 AMD风险； （2）为血浆蛋白CEP加合物开发LC MS/MS分析，以提高精度， CEP测量值作为AMD风险的预测因素。独特的资源支持 拟议的研究包括我们临床记录的大量血浆存储库，广泛 表征AMD和控制供体，我们最先进的蛋白质组学，质谱和基因组 技术，在AMD生物学和世界一流的临床眼科学和基本的十年中 视觉科学研究环境。 ）