Candidate Genes for Primary Open Angle Glaucoma

描述(申请人提供)：青光眼是导致青光眼的主要原因之一。 失明在美国，影响着1500多万人。失明 是由视神经退行性变引起的，通常伴随着 眼压。这种疾病有很大的遗传成分，但 具体涉及的基因尚不清楚。目前的治疗方法是针对 通过降低眼压来减缓视力损失，但不能解决 疾病的分子基础。这个项目的目标是调查 小梁网中差异基因的表达 影响液体排出，进而影响眼压的基因。我们 小梁网组织功能异常的假说 原发性开角型青光眼(POAG)患者 基因在这个组织中的表达模式。我们将使用基因的系列分析 表达(SAGE)分析小梁细胞的转录模式 POAG患者以及年轻(20-40岁)和年龄匹配(50-70岁)的患者 控制。表达水平显著上调或下调的基因 将作为POAG的候选基因进行研究。我们 还将研究其表达水平显著变化的基因 正常人的年龄。这些基因将被绘制成图谱，提供一个极好的 为未来影响疾病基因的位置克隆提供资源 小梁网。然后将对候选基因进行测试，以确定与 以家庭为基础的关联性分析。这款双屏幕差速器 病变组织中的表达及其与疾病意志的统计关联 为确定候选敏感度提供了强有力的机制 基因。然后，最有希望的候选人将在 分子水平，并筛选突变和多态。这个 POAG易感基因的鉴定可为临床诊断提供依据 诊断测试并导致POAG的早期发现和极大的改善 数百万患有这种令人衰弱的疾病的患者的预后。

DESCRIPTION (provided by applicant): Glaucoma is one of the leading causes of blindness in America, and affects over 15 million individuals. Loss of vision is caused by degeneration of the optic nerve, often accompanied by elevated intraocular pressure. There is a large genetic component to this disease, but the specific genes involved are not yet known. Current treatments are aimed at slowing vision loss by reducing intraocular pressure, but do not address the molecular basis of the disease. The goal of this project is to investigate differential gene expression in the trabecular meshwork, in order to identify genes that affect the drainage of fluid, and in turn, intraocular pressure. We hypothesize that the abnormal functioning of trabecular meshwork tissue in patients with primary open angle glaucoma (POAG) is associated with altered patterns of gene expression in this tissue. We will use Serial Analysis of Gene Expression (SAGE) to profile transcription patterns in trabecular meshwork from POAG patients as well as from young (20-40 years) and age-matched (50-70 years) controls. Genes whose expression levels are significantly up- or down-regulated in affected individuals will be investigated as candidate genes for POAG. We will also investigate genes whose expression levels changes significantly with age in normal individuals. These genes will be mapped, providing an excellent resource for future positional cloning of disease genes that affect the trabecular meshwork. Candidate genes will then be tested for association with POAG by family-based association analysis. This double screen-differential expression in affected tissue and statistical association with disease-will provide a powerful mechanism for the identification of candidate susceptibility genes. The most promising candidates will then be characterized at the molecular level and screened for mutations and polymorphisms. The identification of POAG susceptibility genes could provide the basis for diagnostic tests and lead to earlier detection of POAG and a greatly improved prognosis for the millions of patients affected with this debilitating disease.