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新生血管性年龄相关性黄斑变性的玻璃体蛋白质组学

Nobl M, Reich M, Dacheva I, et al.

期刊名称:Experimental Eye Research

卷期:2016年第145卷

摘要

新生血管性年龄相关性黄斑变性(nAMD)已被描述为一种以炎症为主的促血管生成视网膜-脉络膜疾病。玻璃体(V H)与视网膜相邻,可能最好代表nAMD基于蛋白质的介质变化。这项临床实验研究的目的是分析以前未经治疗的患者的VH相关蛋白质组的NAMD,同时根据其临床表现(临床诊断组)对nAMD进行分类。使用毛细管电泳-质谱(CE-MS)以及液相色谱-串联质谱(LC-MS / MS)分析108nNAMD患者和24例特发性飞蚊症对照的VH。共确定了含有至少两个独特肽的101种不同的蛋白质。通过严格的统计分析,我们能够确定可能参与NAMD病理生理的四种蛋白质:丛生蛋白,opticin,色素上皮衍生因子和前列腺素H 2 d异构酶。使用独立样本,确定曲线下ROC-面积可证明结果的有效性:丛生蛋白0.747opticin 0.656,色素上皮衍生因子0.514,前列腺素H2 D-异构酶0.712。此外,还通过ELISA测量进行验证。确定的蛋白质可作为nAMD的潜在生物标志物或甚至治疗靶点。

Neovascular age-related macular degeneration (nAMD) has been described as a predominantly inflammatory and proangiogenic retino-choroidal disease. Vitreous humor (VH) is the adjacent and accessible compartment which, due to the vicinity to the retina, might best represent changes of protein-based mediators of nAMD. The aim of this clinical-experimental study was to analyze the nAMD associated VH proteome of previously untreated patients whilst taking different groups of nAMD into account, based on their clinical presentation (clinical diagnosis groups). Electrophoresis coupled online to mass spectrometry (CE-MS) as well as liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) were used to analyze VH of 108 nAMD patients and 24 controls with idiopathic floaters. A total of 101 different proteins with at least two unique peptides could be identified. Using a stringent statistical analysis with implementation of the closed test principle, we were able to identify four proteins that may be involved in the pathophysiology of nAMD: Clusterin, opticin, pigment epithelium-derived factor and prostaglandin-H2 d-isomerase. Using independent samples, ROC-Area under the curve was determined proving the validity of the results: Clusterin 0.747, opticin 0.656, pigment epithelium-derived factor 0.514, prostaglandin-H2 d-isomerase 0.712. In addition, validation through ELISA measurements was performed. The identified proteins may serve as potential biomarkers or even targets of therapy for nAMD.

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