Genetic Risk Factors for Central Vision Loss in Glaucoma

描述（由申请人提供）：青光眼导致的永久性视野丧失是全球范围内致盲的重要原因。 许多昏迷性视野缺损开始于周边区域，在没有治疗的情况下，它们逐渐扩大，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作为旁中心暗点。患有早期中央视野缺损的青光眼患者在阅读、驾驶方面有更大的困难，并且更有可能因该疾病而失明。重要的是，目前的治疗策略不能预防或恢复涉及中央区的视野缺损患者的功能性视力。最近的研究表明，在疾病的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，其可能是多种遗传和/或环境风险因素的结果。 在这项提案中，我们将使用一种强大的综合方法，利用GWAS、全外显子组测序和途径分析的数据来确定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确定易患早期中央视觉丧失的基因，使其有可能发展为 基于基因的诊断筛查测试，以在不可逆转的损害发生之前识别出处于风险中的个体。 此外，鉴定易患中心视力丧失的基因将提供对可能导致新的预防性治疗的潜在分子事件的了解。

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.