Proteomic Biomarkers for Primary Open Angle Glaucoma

描述(申请人提供)：原发性开角型青光眼(POAG)是导致全球老年人口失明的主要原因之一。减缓或防止这种疾病的发展是一项紧迫的公共卫生目标。我们假设，在POAG易感人群的血液中存在生物标记物，这将使我们能够在疾病的临床证据之前识别出那些处于危险之中的人。建议进行一项病例对照的初步研究，以检验血浆中含有POAG诊断生物标记物的假设。血浆将从来自美国的临床记录的患者中收集，分四个研究组进行，包括一个对照组和三个POAG组(高眼压、可能的POAG和确定的POAG)。酶联免疫吸附试验将用于筛选血浆中可能作为POAG血浆生物标志物的蛋白质氧化修饰。高分辨率MALDI、TOF、TOF和QTOF质谱仪将用于筛选血浆中的蛋白质组模式和/或确定POAG诊断血浆多肽的序列。长期目标是开发用于临床医学的常规诊断技术，以预测POAG的易感性并监测治疗效果，主要是因为今天血清胆固醇测量被用于心血管疾病的风险管理。这项研究将导致早期发现“POAG高危”患者的方法，测量POAG治疗效果的新方法，以及对青光眼病理机制的新见解。公共卫生相关性：原发性开角型青光眼(POAG)是最常见的青光眼形式，影响着大约300万美国人和全球超过7000万人。减缓或防止这种疾病的发展是一项紧迫的公共卫生目标。这项拟议的研究将导致早期发现“POAG高危”患者的方法，测量POAG治疗效果的新方法，以及对青光眼病理机制的新见解。

DESCRIPTION (provided by applicant): Primary open angle glaucoma (POAG) is one of the leading causes of blindness in the elderly population worldwide. Slowing or preventing the progression of this disease is an urgent public health goal. We hypothesize that biomarkers exist in the blood of individuals susceptible to developing POAG that will allow identification of those at risk prior to clinical evidence of the disease. A case-control pilot study is proposed to test the hypothesis that plasma contains diagnostic biomarkers for POAG. Plasma will be collected from clinically documented patients from the United States in four study groups, including a control group and three POAG groups (ocular hypertension, possible POAG and definite POAG). ELISA will be used to screen plasma for protein oxidative modifications that may serve as POAG plasma biomarkers. High resolution MALDI TOF TOF and QTOF mass spectrometry will be used to screen plasma for proteomic patterns and/or to determine the sequence of POAG diagnostic plasma peptides. The long term goal is the development of routine diagnostic technology for use in clinical medicine to predict POAG susceptibility and to monitor therapeutic efficacy, essentially as serum cholesterol measurements are used today for risk management for cardiovascular disease. This research will lead to methods for early detection of "POAG at risk" individuals, new methods for measuring POAG therapeutic efficacies and new insights into mechanisms of glaucoma pathology. PUBLIC HEALTH RELEVANCE: Primary open angle glaucoma (POAG) is the most common form of glaucoma and affects about 3 million Americans and over 70 million people worldwide. Slowing or preventing the progression of this disease is an urgent public health goal. The proposed research will lead to methods for early detection of "POAG at risk" individuals, new methods for measuring POAG therapeutic efficacies and new insights into the mechanisms of glaucoma pathology.