Proteomic Biomarkers of Intraocular Infection

眼内感染的蛋白质组生物标志物

• 批准号: 10459542
• 负责人: ALEXANDER G BASSUK
• 金额: $ 39.77万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10459542
• 关键词: Antibodies; Autoimmune; Bacteria; Biological Markers; Biopsy; Biopsy Specimen; Biotin; Blindness; Characteristics; Computer software; Custom; Data; Devices; Diagnosis; Diagnostic; Diagnostic tests; Disease; ERM protein; Endophthalmitis; Enzyme-Linked Immunosorbent Assay; Etiology; Eye diseases; Foundations; Glass; Goals; Human; Immune response; Immunologics; Infection; Inflammation; LCN2 gene; LCP1 gene; Laboratory culture; Lead; Liquid substance; MMP8 gene; MMP9 gene; Mass Spectrum Analysis; Measures; Molecular; Molecular Diagnostic Testing; Molecular Profiling; Morbidity - disease rate; Online Systems; Operating Rooms; Parasites; Patients; Phenotype; Precision Health; Proteins; Proteome; Proteomics; Public Health; Rapid diagnostics; Research; Retina; S100A8 gene; Sampling; Specimen; Testing; Tissues; Uveitis; Validation; Viral; Virus; Vision; Visual; aqueous; autoinflammatory; bacterial endophthalmitis; base; biobank; candidate identification; candidate marker; candidate validation; clinical development; clinical examination; diagnostic tool; eye preservation; falls; fungus; lens; liquid biopsy; microbial; novel; personalized diagnostics; point of care; prevent; prospective; protein biomarkers; relational database; research clinical testing; specific biomarkers; tool

Project Summary Intraocular infections due to bacteria, viruses, fungi, and parasites (infectious endophthalmitis) are among the most common and visually devasting causes of blindness. Endophthalmitis has high morbidity because the retina is intolerant of immunologic insult. Since initial clinical examination cannot determine the cause of intraocular inflammation (uveitis), doctors must wait for laboratory culture to identify a microbial agent. But waiting days to weeks for cultures to grow delays diagnosis and treatment, frequently results in debilitating visual morbidity and blindness. The proteome of adjacent vitreous can be characterized to uncover biomarkers for specific etiologies of uveitis. Since different causes of intraocular infection elicit different immune responses, we hypothesize that proteomic profile of the inflamed vitreous may reflect key molecular changes and guide diagnosis of intraocular infections. Our group has used large-scale proteomic platforms to analyze the protein signature in liquid vitreous biopsies from endophthalmitis patients. This approach allowed us to identify several candidate protein biomarkers that differentiate infectious from non-infectious uveitis and specific infectious types of endophthalmitis, including bacterial, viral, and fungal endophthalmitis. Our long-term goal is to find better and more specific molecular treatments for vitreoretinal disease. Our objective in this proposal is to use targeted proteomic platforms to validate sensitive and specific biomarkers that reliably differentiate different types of intraocular infection (e.g. bacterial, viral, and fungal). Our central hypothesis is that vitreous protein signatures can differentiate between non-infectious and infectious uveitis and the class of infection more-rapidly than conventional clinical testing. Our studies will test the hypothesis through two specific aims: (1) Validate proteomic biomarkers that differentiate infectious from non-infectious uveitis and (2) biomarkers that differentiate different classes of intraocular infection (e.g. bacterial, viral, and fungal). Impact. We expect that successful completion of these aims will validate sensitive and specific endophthalmitis biomarkers and lay the foundation for the development of clinical diagnostic tests for intraocular infection.

项目摘要 由细菌、病毒、真菌和寄生虫引起的眼内感染（感染性眼内炎）是常见的眼内感染。 最常见的和视觉破坏性的失明原因。眼内炎发病率高，因为 视网膜不能耐受免疫损伤。由于最初的临床检查无法确定 眼内炎症（葡萄膜炎），医生必须等待实验室培养，以确定微生物病原体。但 等待培养物生长数天至数周会延误诊断和治疗， 视觉疾病和失明。邻近玻璃体的蛋白质组可以被表征以揭示生物标志物 葡萄膜炎的具体病因。由于眼内感染的不同原因引起不同的免疫反应， 反应，我们假设，蛋白质组学的轮廓发炎玻璃体可能反映了关键的分子变化 并指导眼内感染的诊断。我们的团队使用大规模的蛋白质组学平台来分析 眼内炎患者液体玻璃体活检中的蛋白质特征。这种方法使我们能够 鉴定区分感染性和非感染性葡萄膜炎的几种候选蛋白质生物标志物， 特定感染性眼内炎，包括细菌性、病毒性和真菌性眼内炎。我们的长期 目的是为玻璃体视网膜疾病找到更好和更特异的分子治疗方法。我们的目标是 一项建议是使用靶向蛋白质组学平台来验证可靠的敏感和特异性生物标志物， 区分不同类型的眼内感染（例如细菌、病毒和真菌）。我们的核心假设是 玻璃体蛋白特征可以区分非感染性和感染性葡萄膜炎， 比传统的临床试验更快地感染。我们的研究将通过两个方面来验证这一假设 具体目的：（1）鉴别感染性和非感染性葡萄膜炎的蛋白质组学生物标志物，和（2） 区分不同类型眼内感染（例如细菌、病毒和真菌）的生物标志物。冲击 我们期望这些目标的成功完成将验证敏感性和特异性眼内炎 生物标志物，并为眼内感染的临床诊断测试的发展奠定基础。