Koss Michael Janusz, Hoffmann Janosch, Nguyen Nauke, Pfister Marcel, Mischak Harald, Mullen William, Husi Holger, Rejdak Robert, Koch Frank, Jankowski Joachim, Krueger Katharina, Bertelmann Thomas, Klein Julie, Schanstra Joost P, Siwy Justyna
Department of Ophthalmology, Goethe University, Frankfurt am Main, Germany; Doheny Eye Institute, Los Angeles, California, United States of America; Department of Ophthalmology, Ruprecht Karls University, Heidelberg, Germany.
Mosaiques Diagnostics, Hannover, Germany.
PLoS One. 2014 May 14;9(5):e96895. doi: 10.1371/journal.pone.0096895. eCollection 2014.
There is absence of specific biomarkers and an incomplete understanding of the pathophysiology of exudative age-related macular degeneration (AMD).
Eighty-eight vitreous samples (73 from patients with treatment naïve AMD and 15 control samples from patients with idiopathic floaters) were analyzed with capillary electrophoresis coupled to mass spectrometry in this retrospective case series to define potential candidate protein markers of AMD. Nineteen proteins were found to be upregulated in vitreous of AMD patients. Most of the proteins were plasma derived and involved in biological (ion) transport, acute phase inflammatory reaction, and blood coagulation. A number of proteins have not been previously associated to AMD including alpha-1-antitrypsin, fibrinogen alpha chain and prostaglandin H2-D isomerase. Alpha-1-antitrypsin was validated in vitreous of an independent set of AMD patients using Western blot analysis. Further systems biology analysis of the data indicated that the observed proteomic changes may reflect upregulation of immune response and complement activity.
Proteome analysis of vitreous samples from patients with AMD, which underwent an intravitreal combination therapy including a core vitrectomy, steroids and bevacizumab, revealed apparent AMD-specific proteomic changes. The identified AMD-associated proteins provide some insight into the pathophysiological changes associated with AMD.
渗出性年龄相关性黄斑变性（AMD）缺乏特异性生物标志物，且对其病理生理学的理解不完整。
在这个回顾性病例系列中，对88份玻璃体样本（73份来自未经治疗的AMD患者，15份对照样本来自特发性飞蚊症患者）进行了毛细管电泳结合质谱分析，以确定AMD潜在的候选蛋白质标志物。发现19种蛋白质在AMD患者的玻璃体中上调。大多数蛋白质来源于血浆，参与生物（离子）转运、急性期炎症反应和血液凝固。一些蛋白质以前未与AMD相关联，包括α-1-抗胰蛋白酶、纤维蛋白原α链和前列腺素H2-D异构酶。使用蛋白质印迹分析在一组独立的AMD患者的玻璃体中验证了α-1-抗胰蛋白酶。对数据的进一步系统生物学分析表明，观察到的蛋白质组学变化可能反映免疫反应和补体活性的上调。
对接受包括核心玻璃体切除术、类固醇和贝伐单抗在内的玻璃体腔内联合治疗的AMD患者的玻璃体样本进行蛋白质组分析，发现了明显的AMD特异性蛋白质组学变化。鉴定出的与AMD相关的蛋白质为与AMD相关的病理生理变化提供了一些见解。
