Genetic Risk Factors for Central Vision Loss in Glaucoma

青光眼中央视力丧失的遗传风险因素

基本信息

批准号：
8510304
负责人：
Janey L Wiggs
金额：
$ 24.43万
依托单位：
MASSACHUSETTS EYE AND EAR INFIRMARY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-03-01 至 2015-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8510304
关键词：
Affect Automobile Driving Blindness Blood Vessels Chromosomes, Human, Pair 4 Collaborations Data Data Set Defect Development Diagnostic Disease Early Diagnosis Early treatment Environmental Risk Factor Etiology Evaluation Event Functional disorder GUCY1A3 gene GUCY1B3 gene Genes Genetic Genetic Epistasis Genotype Glaucoma Goals Human Genetics Individual Lead Link Maintenance Measures Medical Molecular Operative Surgical Procedures Paracentral Scotomas Pathogenesis Pathway Analysis Pathway interactions Patients Pattern Peripheral Phenotype Physiologic Intraocular Pressure Prevention strategy Primary Open Angle Glaucoma Primary Prevention Public Health Reading Research Retinal Risk Risk Factors Scotoma Sequence Analysis Siblings Staging Subgroup Sum Susceptibility Gene Testing Therapeutic Intervention Variant Vision Visual Fields Weight Work base blind case control central visual field early onset endophenotype exome exome sequencing ganglion cell genetic risk factor genetic variant genome wide association study genome-wide insight interest novel optic nerve disorder prevent public health relevance screening trait treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Permanent visual field loss from glaucoma is a significant cause of blindness worldwide. Many glaucomatous visual field defects begin in the peripheral regions where, without treatment, they gradually enlarge to eventually damage the central high acuity zone that is critically important for normal function. Current medical and surgical treatment can slow the progression of peripheral visual field defects, limiting damage to the central field and preserving functional vision for many glaucoma patients. However, in many glaucoma patients the initial functional defect appears in the central visual field as a paracentra scotoma. Glaucoma patients presenting with early-stage central visual field defects have more difficulty reading, driving and are more likely to become blind from the disease. Importantly, current treatment strategies can not prevent or restore functional vision in patients that develop visual field defects involving the central regions. Recent studies have shown that glaucoma patients with central visual field defects at early stages of the disease have common features defining a glaucoma endophenotype that is likely the result of multiple genetic and/or environmental risk factors. In this proposal we will use a powerful integrated approach to identify genetic risk factors contributing to central vision loss in glaucoma using data from GWAS, whole exome sequencing and pathway analysis. The ultimate goal of this research is to identify genes that predispose to early-stage loss of central vision, making it possible to develop gene-based diagnostic screening tests to identify individuals at risk before irreversible damage has occurred. Additionally, the identification of genes that predispose to central vision loss wil provide insight into the responsible underlying molecular events which could lead to new preventative therapies.

描述（由申请人提供）：青光眼造成的永久性视野丧失是全世界失明的重要原因。许多青光眼视野缺损始于周边区域，如果不进行治疗，它们会逐渐扩大，最终损害对正常功能至关重要的中央高视力区。目前的药物和手术治疗可以减缓周边视野缺损的进展，限制对中央视野的损害并保留许多青光眼患者的功能性视力。然而，在许多青光眼患者中，最初的功能缺陷出现在中央视野中，表现为中心暗点。患有早期中央视野缺陷的青光眼患者阅读、驾驶更加困难，并且更有可能因该疾病而失明。重要的是，当前的治疗策略不能预防或恢复出现涉及中心区域视野缺损的患者的功能性视力。最近的研究表明，在疾病早期阶段具有中央视野缺陷的青光眼患者具有定义青光眼内表型的共同特征，这可能是多种遗传和/或环境危险因素的结果。在本提案中，我们将利用 GWAS、全外显子组测序和通路分析的数据，使用强大的综合方法来识别导致青光眼中心视力丧失的遗传风险因素。这项研究的最终目标是找出导致早期中央视力丧失的基因，从而使发展成为可能基于基因的诊断筛查测试，可在发生不可逆转的损害之前识别出处于危险中的个体。此外，识别导致中央视力丧失的基因将有助于深入了解潜在的分子事件，从而可能导致新的预防性疗法。