Proteomic Biomarkers of Intraocular Infection

项目摘要 由细菌、病毒、真菌和寄生虫(传染性眼内炎)引起的眼内感染是 最常见且极具视觉破坏性的失明原因。眼内炎的发病率很高，因为 视网膜不能忍受免疫学上的侮辱。因为最初的临床检查不能确定 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制剂。但 等待几天到几周的培养延迟诊断和治疗，往往会导致虚弱 视力障碍和失明。邻近玻璃体的蛋白质组可用于揭示生物标志物。 针对葡萄膜炎的特定病因。由于不同的眼内感染原因会引起不同的免疫反应 我们推测，发炎的玻璃体的蛋白质组特征可能反映了关键的分子变化。 并指导眼内感染的诊断。我们小组已经使用大规模蛋白质组平台来分析 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 确定几个区分感染性和非感染性葡萄膜炎的候选蛋白质生物标志物 眼内炎的特定感染类型，包括细菌性、病毒性和真菌性眼内炎。我们的长期合作 目标是找到更好、更特异的玻璃体视网膜疾病的分子治疗方法。我们的目标是 建议使用靶向蛋白质组平台来验证敏感和特定的生物标记物 区分不同类型的眼内感染(例如细菌、病毒和真菌)。我们的中心假设是 玻璃体蛋白信号可以区分非感染性和感染性葡萄膜炎以及 感染速度比常规临床检测更快。我们的研究将通过两个方面来检验这一假说 具体目标：(1)验证区分感染性和非感染性葡萄膜炎的蛋白质组生物标志物和(2) 区分不同类别眼内感染的生物标志物(例如细菌、病毒和真菌)。冲击力。 我们期望这些目标的成功完成将验证敏感和特定的眼内炎。 为发展眼内感染的临床诊断试验奠定了基础。

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.