Yu Jing, Feng Le, Wu Yan, Wang Hao, Ba Jun, Zhu Wei, Xie Chunlei
Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P. R. China.
Mol Biosyst. 2014 Oct;10(10):2558-66. doi: 10.1039/c4mb00240g.
To understand the molecular mechanisms of idiopathic epiretinal membranes (iERMs), the vitreous proteomes of patients with iERMs were investigated. The vitreous proteome in patients with iERMs (n = 8) and donor samples (n = 8) was analysed using reversed phase high-performance liquid chromatography (RP-HPLC) coupled with electrospray ionization tandem mass spectrometry (ESI-MS/MS) and GeneGo Metacore™. This research followed the tenets of the Declaration of Helsinki for the use of human subjects. In this current study, 226 significant changes in protein abundance (abundance ratio >2, p < 0.01) were identified in the vitreous proteome of iERM patients compared to normal control vitreous, including 122 proteins that were present at lower levels and 104 proteins that were present at higher levels. In the iERM vitreous samples, complement components, inflammation-related proteins and matrix metalloproteinase were present at higher levels, while normal cytoskeleton proteins were present at lower levels. The top GeneGo pathway was "immune response", the top process network was "inflammation", and the top KEGG pathway was "coagulation cascades". The essential 2-node proteins of the network were estrogen receptor 1 (ESR1) and p300. Among those found at higher levels, ubiquitin-conjugating enzyme E2O (UBE2O) and complement C4A (C4A) were the most abundant proteins, and could be detected in each of the iERM vitreous samples. It can be concluded that iERMs are a complicated pathological process involving inflammation, immune response, and cytoskeleton remolding. UBE2O and C4A may be candidate biomarkers for iERMs.
为了解特发性视网膜前膜（iERM）的分子机制，对iERM患者的玻璃体蛋白质组进行了研究。采用反相高效液相色谱（RP-HPLC）结合电喷雾电离串联质谱（ESI-MS/MS）和GeneGo Metacore™分析了iERM患者（n = 8）和供体样本（n = 8）的玻璃体蛋白质组。本研究遵循了《赫尔辛基宣言》中关于使用人类受试者的原则。在本研究中，与正常对照玻璃体相比，iERM患者的玻璃体蛋白质组中鉴定出226种蛋白质丰度的显著变化（丰度比>2，p < 0.01），其中122种蛋白质水平较低，104种蛋白质水平较高。在iERM玻璃体样本中，补体成分、炎症相关蛋白和基质金属蛋白酶水平较高，而正常细胞骨架蛋白水平较低。GeneGo通路中排名第一的是“免疫反应”，过程网络中排名第一的是“炎症”，KEGG通路中排名第一的是“凝血级联反应”。该网络的关键双节点蛋白是雌激素受体1（ESR1）和p300。在水平较高的蛋白质中，泛素结合酶E2O（UBE2O）和补体C4A（C4A）是最丰富的蛋白质，并且可以在每个iERM玻璃体样本中检测到。可以得出结论，iERM是一个涉及炎症、免疫反应和细胞骨架重塑的复杂病理过程。UBE2O和C4A可能是iERM的候选生物标志物。
