METHODS: We detected proteins in the aqueous humor of 14 untreated, four refractory, and four post-operative patients with BRVO-ME and 12 age-matched cataract controls using four-dimensional label-free proteomic and bioinformatics analyses.
RESULTS: In total, 84 proteins exhibited significant differential expression between the BRVO and control samples (fold change [FC] ≥ 1.2 and adjusted p-value < 0.05). Compared to the control group, 43 and 41 proteins were upregulated and downregulated, respectively, in the BRVO group. These proteins were involved in cell adhesion, visual perception, retina homeostasis, and platelet activation. Several significantly enriched signaling pathways included complement and coagulation cascades and platelet activation. In the protein-protein interaction networks generated using the search tool for retrieval of interacting genes (STRING), the fibrinogen alpha chain and fibrinogen beta chain constituted a tightly connected cluster. Many common protein expression trends, such as the fibrinogen alpha chain and fibrinogen beta chain, were observed in both the recurrent and refractory groups. Differentially expressed proteins in the two groups were involved in complement activation, acute-phase response, platelet activation, and platelet aggregation. Important signaling pathways include the complement and coagulation cascades, and platelet activation. Protein-protein interaction analysis suggested that the fibrinogen alpha chain and fibrinogen beta chain constituted a tightly connected cluster. The expression of some differentially expressed proteins shared by the BRVO and the recurrent and refractory groups was reversed in the post-operative group.
CONCLUSIONS: Our study is the first to analyze the proteomics of recurrent, refractory, and post-operative groups treated for BRVO-ME, and may potentially provide novel therapeutic interventions for the recurrence of ME.
方法:我们检测到14个未处理的房水中的蛋白质,四种耐火材料,4例BRVO-ME术后患者和12例年龄匹配的白内障对照患者使用四维无标记蛋白质组学和生物信息学分析。
结果:总计,84种蛋白质在BRVO和对照样品之间表现出显著差异表达(倍数变化[FC]≥1.2和调整后的p值<0.05)。与对照组相比,43和41种蛋白质被上调和下调,分别,在BRVO组。这些蛋白质参与细胞粘附,视觉感知,视网膜稳态,和血小板活化。几个显著富集的信号通路包括补体和凝血级联和血小板活化。在使用检索相互作用基因(STRING)的搜索工具生成的蛋白质-蛋白质相互作用网络中,纤维蛋白原α链和纤维蛋白原β链构成了紧密相连的簇。许多常见的蛋白质表达趋势,如纤维蛋白原α链和纤维蛋白原β链,在复发和难治性组中都观察到。两组差异表达蛋白均参与补体激活,急性期反应,血小板活化,和血小板聚集。重要的信号通路包括补体和凝血级联,和血小板活化。蛋白质相互作用分析表明,纤维蛋白原α链和纤维蛋白原β链构成了紧密相连的簇。在术后组中,BRVO和复发和难治性组共有的一些差异表达蛋白的表达被逆转。
结论:我们的研究是第一个分析复发性疾病的蛋白质组学,耐火材料,和接受BRVO-ME治疗的术后组,并可能为ME复发提供新的治疗干预措施。