Dacheva I, Reich M, Nobl M, Ceglowska K, Wasiak J, Siwy J, Zürbig P, Mischak H, Koch F H J, Kopitz J, Kretz F T A, Tandogan T, Auffarth G U, Koss M J
Universitätsaugenklinik Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Deutschland.
Augenklinik, Albert-Ludwigs-University Freiburg, Freiburg, Deutschland.
Ophthalmologe. 2018 Mar;115(3):203-215. doi: 10.1007/s00347-017-0469-z.
The pathophysiological mechanisms of macular edema secondary to branch retinal vein occlusion (BRVO) remain unclear.
To analyze the protein profile of human vitreous of patients with BRVO and to identify specific dysregulated proteins.
Undiluted vitreous humor samples from patients with treatment naïve BRVO and 15 controls with idiopathic floaters were analyzed in this clinical-experimental study using capillary electrophoresis coupled to a mass spectrometer (CE-MS) and tandem mass spectrometry (MS/MS). Quantitative analysis of the dysregulated proteins was performed with enzyme-linked immunosorbent assay (ELISA). Protein-protein interactions were depicted with the STRING database.
A total of 84 proteins were found in the human vitreous samples of 15 patients with BRVO and 15 controls. In all, 14 proteins were significant when comparing the signal intensities of BRVO and control samples. Six significant dysregulated proteins with p < 0.001 were further verified with ELISA. Clusterin, complement factor C3, prostaglandin-H2 D‑isomerase and vitronectin were significantly upregulated in the BRVO group and opticin was downregulated. The protein interactions analysis showed associations with inflammatory cascades, matrix changes, mechanisms of cell survival und death.
The results of the study reveal that the proteomic composition of vitreous humor differed significantly between the patients with BRVO and the controls. Whether the identified proteins may serve as potential biomarkers for pathophysiology, diagnostics or therapy should be examine in further studies.
视网膜分支静脉阻塞（BRVO）继发黄斑水肿的病理生理机制尚不清楚。
分析BRVO患者人玻璃体的蛋白质谱，并鉴定特定的失调蛋白。
在这项临床实验研究中，使用毛细管电泳联用质谱仪（CE-MS）和串联质谱（MS/MS）分析了未经治疗的BRVO患者的未稀释玻璃体液样本以及15名患有特发性飞蚊症的对照者的样本。采用酶联免疫吸附测定（ELISA）对失调蛋白进行定量分析。用STRING数据库描绘蛋白质-蛋白质相互作用。
在15例BRVO患者和15名对照者的人玻璃体样本中总共发现了84种蛋白质。比较BRVO和对照样本的信号强度时，共有14种蛋白质具有显著性差异。用ELISA进一步验证了6种p<0.001的显著失调蛋白。簇集蛋白、补体因子C3、前列腺素-H2 D-异构酶和玻连蛋白在BRVO组中显著上调，而视蛋白下调。蛋白质相互作用分析显示与炎症级联反应、基质变化、细胞存活和死亡机制有关。
研究结果表明，BRVO患者与对照者的玻璃体液蛋白质组组成存在显著差异。所鉴定的蛋白质是否可作为病理生理学、诊断或治疗的潜在生物标志物，有待进一步研究。
