Proteomic Biomarkers for Glaucomatous Optic Neuropathy

青光眼视神经病变的蛋白质组生物标志物

• 批准号: 10329956
• 负责人: Ashok Sharma
• 金额: $ 37.35万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10329956
• 关键词: Address; Age; Anterior; Apoptosis; Aqueous Humor; Area; Awareness; Binding Proteins; Bioinformatics; Biological; Biological Markers; Biological Process; Blindness; Blood; Body Fluids; Cataract; Cataract Extraction; Cell physiology; Cells; Characteristics; Ciliary Body; Clinical; Clinical Data; Computer software; Consent; Cornea; Data; Databases; Detection; Development; Diagnostic; Disease; Disease Management; Electrolytes; Epithelial; Excision; Eye; Eye diseases; Family; Foundations; Future; Generations; Glaucoma; Glycoproteins; Homeostasis; Human; Image; Immunity; Individual; Infection; Inflammation; Internet; Investigation; Laboratories; Lead; Link; Liquid substance; Maintenance; Malignant Neoplasms; Mass Spectrum Analysis; Measures; Medical; Metabolic; Modality; Molecular; Morphology; Nerve; Nutrient; Operative Surgical Procedures; Ophthalmologist; Optic Nerve; Oxygen; Pathway interactions; Patients; Persons; Physiologic Intraocular Pressure; Plasma; Polysaccharides; Post-Translational Protein Processing; Prevention; Prognostic Marker; Protein Glycosylation; Proteins; Proteome; Proteomics; Race; Research; Research Personnel; Retinal Ganglion Cells; Risk; Risk Factors; Sampling; Shapes; Site; Source; Speed; Statistical Models; Structural defect; Structure; Symptoms; Technology; Therapeutic; Thick; Time; Tissues; Trabecular meshwork structure; Variant; Vertebral column; Visual Fields; Visualization; Water; aqueous; base; burden of illness; data integration; data reuse; diagnostic biomarker; digital repositories; frontier; glaucoma surgery; global health; glycoproteomics; glycosylation; improved; infancy; instrument; liquid chromatography mass spectrometry; mass spectrometer; nerve damage; new technology; novel marker; optic nerve disorder; posterior eyeball chamber; prognostic tool; retinal nerve fiber layer; sex; social; tool; translational impact; treatment strategy; wasting; web site

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.

项目概要/摘要 青光眼是一种导致永久性视力丧失的眼部疾病。在大多数情况下，青光眼没​​有 早期症状，并在神经损伤和视力丧失不可逆转时被发现。如果全球预测 预计到 2020 年，将有 7600 万人患有青光眼。眼内压（IOP）升高是主要风险 青光眼的因素。不幸的是，眼压升高并不总是具有预测性，因为一些青光眼患者 眼压正常，而其他眼压升高的个体则没有表现出这种疾病。青光眼检测和 疾病管理是该领域的一项重大挑战，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患有青光眼，而其他患者则看起来没有 就像他们没有患有青光眼，但实际上正处于疾病的早期阶段。 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。 鉴定青光眼、蛋白质和其他分子之间的关系将为更好地治疗奠定基础。 诊断方式、改进治疗策略、预防失明，从而减少全球 这种疾病的健康负担。 房水 (AH) 是一种液体，当它从眼球流出时，它会沐浴眼睛前部的几乎所有结构。 从睫状体到其出口的源头：小梁网。一些 AH 蛋白源自睫状体 同时在水性组分内。其他的则随着液体在周围循环而被拾取 健康和不健康的眼组织。该提案旨在定量分析这些 AH 蛋白并 确定它们与青光眼视神经病变之间的关系。这种液体可以安全地 在白内障和青光眼手术期间收集，通常被丢弃。我们将收集医疗、社会 以及同意白内障和青光眼手术患者的临床数据。一些临床参数将 从最先进的仪器获得，可产生神经层的高清图像和 配置。 AH 中的蛋白质将使用最新一代质量进行鉴定和定量 光谱测定法并与临床数据进行统计比较。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。根据这些数据，我们将开发统计模型 努力识别有视神经病变风险的个体。我们的目标是使用蛋白质数据来帮助分类 青光眼家族的亚型。最后，我们将开发一个公开的互联网可访问数据库 我们将用我们的蛋白质发现来填充 AH 蛋白质。该数据库也可能成为 电子存储库的主干，以实现不同科学实验室之间的数据集成。这 方法应使全球青光眼调查能够更有效地进行，最终减少 失明的负担。

项目成果

Survey of Microinvasive Glaucoma Surgery and Other Glaucoma Surgical Experience among United States Ophthalmology Residency Programs.

• DOI: 10.1055/s-0040-1721072
• 发表时间: 2021-07
• 期刊: Journal of academic ophthalmology (2017)
• 作者: Halenda, Kevin M;Lee, Tae Jin;Sharma, Ashok;Estes, Amy J;Bollinger, Kathryn E
• 通讯作者: Bollinger, Kathryn E