Proteomic Biomarkers for Glaucomatous Optic Neuropathy

项目总结/摘要 青光眼是一种导致永久性视力丧失的眼部疾病。青光眼，在大多数情况下， 早期症状，并在神经损伤和视力丧失不可逆转时检测到。如果全球预测 到2020年将有7600万青光眼患者。眼内压（IOP）升高是一个主要风险 青光眼的治疗方法不幸的是，眼压升高并不总是预测，因为一些青光眼患者 正常的IOP，而其他IOP升高的个体不表现出疾病。青光眼检测和 疾病管理是该领域的重大挑战，许多临床问题仍未解决。之一 最大的问题是，一些患者的眼睛看起来像青光眼，而另一些患者的眼睛看起来像青光眼， 就像他们没有青光眼，但实际上是在疾病的早期阶段。 青光眼研究的最新前沿是研究眼部蛋白质与视力丧失的关系。 确定青光眼、蛋白质和其他分子之间的关系将为更好地治疗青光眼奠定基础。 诊断模式，改进的治疗策略，预防失明，从而减少全球 这种疾病的健康负担。 房水（AH）是一种流体，当其从眼前部流出时，其几乎沐浴眼睛前部的所有结构。 从睫状体的源到其出口：小梁网。一些AH蛋白起源于睫状体 同时在水溶液中。另一些则是在液体循环时被吸收的 健康和不健康的眼组织。该建议旨在定量分析这些AH蛋白， 探讨它们与青光眼视神经病变的关系。这种液体可以安全地 在白内障和青光眼手术中收集，通常被丢弃。我们将收集医疗，社会 和同意的白内障和青光眼手术患者的临床数据。一些临床参数将 从产生神经层的高清晰度图像的现有技术仪器获得， 配置. AH中的蛋白质将使用最新一代质量 光谱分析并与临床数据进行统计学比较。将进行生物信息学分析，以揭示 与蛋白质改变相关的细胞功能。基于这些数据，我们将开发统计模型， 一项旨在识别有视神经病变风险的个体的努力。我们的目标是利用蛋白质数据来帮助分类 青光眼家族中的亚型。最后，我们将建立一个公开的互联网访问数据库， 所有的蛋白质我们都将用我们的蛋白质发现来填充。该数据库也可能成为 电子储存库的主干，使不同的科学实验室之间的数据集成。这 这种方法应该使全球青光眼调查更有效地进行，最终减少 盲目的负担

Project Summary/Abstract Glaucoma is a family of eye disorders which causes permanent vision loss. Glaucoma, in most cases, has no early symptoms and is detected when the nerve damage and vision loss is irreversible. If global projections hold by 2020 there will be 76 million people with glaucoma. Elevated intraocular pressure (IOP) is a major risk factor for glaucoma. Unfortunately, elevated IOP is not always predictive as some glaucoma patients have normal IOP, while other individuals with elevated IOP do not manifest the disease. Glaucoma detection and disease management is a significant challenge in the field and many clinical issues remain unsolved. One of the biggest issues is that the eyes of some patients look like they have glaucoma and don’t while others look like they don’t have glaucoma but in fact are in the early stages of the disease. The newest frontier in glaucoma research is investigation of how ocular proteins relate to vision loss. Identification of relationship between glaucoma, proteins and other molecules will set the stage for better diagnostic modalities, improved treatment strategies, blindness prevention and therefore, reduce the global health burden of this disease. Aqueous humor (AH) is a fluid which bathes nearly all structures in the front of the eye as it flows from its source at the ciliary body to its exit: the trabecular meshwork. Some AH proteins originate from the ciliary body simultaneously within the aqueous component. Others are picked up as the fluid circulates through and around healthy and unhealthy ocular tissues. This proposal aims to quantitatively analyze these AH proteins and determine the relationship between them and glaucomatous optic neuropathy. This fluid can be safely collected during cataract and glaucoma surgeries where it is usually discarded. We will collect medical, social and clinical data on consenting cataract and glaucoma surgical patients. Some clinical parameters will be obtained from state of the art instruments which produce high definition images of nerve layers and configurations. The proteins in the AH will be identified and quantified using the latest generation mass spectrometry and statistically compared to clinical data. Bioinformatics analyses will be performed to reveal the cellular functions associated with protein alterations. Based on these data we will develop statistical models in an effort to identify individuals at risk for optic neuropathy. We aim to use the protein data to help classify subtypes in the family of glaucoma. Finally, we will develop a publicly available internet accessible database of AH proteins which we will populate with our protein discoveries. This database may also become part of the backbone of an electronic repository to enable data integration across different scientific laboratories. This approach should allow global glaucoma investigations to proceed more effectively eventually reducing the burden of blindness.