Genetic Risk Factors for Central Vision Loss in Glaucoma

描述(申请人提供)：青光眼导致的永久性视野丧失是全世界失明的一个重要原因。许多青光眼视野缺陷开始于周围区域，在没有治疗的情况下，它们会逐渐扩大，最终损害对正常功能至关重要的中央高敏感区。目前的内科和外科治疗可以减缓周边视野缺陷的进展，限制对中央视野的损害，并保护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，表现为旁中心暗点。表现为早期中央视野缺陷的青光眼患者阅读、驾驶更困难，更有可能因此而失明。重要的是，目前的治疗策略不能预防或恢复累及中央区域的视野缺陷患者的功能性视力。最近的研究表明，在疾病的早期阶段有中央视野缺陷的青光眼患者具有共同的特征，即青光眼的内表型可能是多种遗传和/或环境危险因素的结果。在这项提案中，我们将使用一种强大的综合方法来识别导致青光眼中心视力丧失的遗传风险因素，使用来自GWAS的数据、整个外显子组测序和路径分析。这项研究的最终目标是确定易导致早期中央视力丧失的基因，使其有可能发展 基于基因的诊断筛查测试，在不可逆转的损害发生之前识别处于风险中的个人。此外，对易导致中心性视力丧失的基因的识别将提供对可能导致新的预防性治疗的潜在分子事件的洞察。

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.