Quantitative Proteomics Analysis of Vitreous Humor from Diabetic Retinopathy Patients
Quantitative Proteomics Analysis of Vitreous Humor from Diabetic Retinopathy Patients
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DOI：
10.1021/acs.jproteome.5b00900
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发表时间：
2015-12-01
影响因子：
4.4
通讯作者：
Varjosalo, Markku
中科院分区：
文献类型：
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作者：
Loukovaara, Sirpa;Nurkkala, Helka;Varjosalo, Markku
糖尿病视网膜病变（DR）的初始触发因素是高血糖诱导的氧化应激和晚期糖基化终产物。大多数病理结构变化发生在视网膜微血管系统中，但DR的总体发展是多因素的，具有微血管、神经退行性、遗传/表观遗传、免疫和继发性炎症相关因素的复杂相互作用。虽然有几个单独的因素和途径与视网膜病变有关，但缺乏对该疾病的系统水平的了解。为了解决这一问题，我们进行了基于质谱的无标记定量蛋白质组学分析的138玻璃体液样本的非增殖性DR或更严重的增殖形式的疾病。此外，我们分析了两组接受抗VEGF（血管内皮生长因子）（贝伐单抗）治疗的患者的样本。在我们的研究中，我们鉴定了2482种玻璃体蛋白，并定量了1351种玻璃体蛋白的缺失。其中，230种蛋白质在增殖性视网膜病变中的表达显著高于非增殖性视网膜病变。这种特定的蛋白质亚群与炎症、补体和凝血级联蛋白、蛋白酶抑制剂、载脂蛋白、免疫球蛋白和细胞粘附分子相关，反映了疾病的多因素性质。确定疾病的关键分子对于开发新的治疗分子和现有药物的新用途至关重要。无标记定量
Initial triggers for diabetic retinopathy (DR) are hyperglycemia-induced oxidative stress and advanced glycation end-products. The most pathological structural changes occur in retinal microvasculature, but the overall development of DR is multifactorial, with a complex interplay of microvascular, neurodegenerative, genetic/epigenetic, immunological, and secondary inflammation-related factors. Although several individual factors and pathways have been associated with retinopathy, a systems level understanding of the disease is lacking. To address this, we performed mass spectrometry based label-free quantitative proteomics analysis of 138 vitreous humor samples from patients with nonproliferative DR or the more severe proliferative form of the disease. Additionally, we analyzed samples from anti-VEGF (vascular endothelial growth factor) (bevacizumab)-treated patients from both groups. In our study, we identified 2482 and quantified the abundancy of 1351 vitreous proteins. Of these, the abundancy of 230 proteins was significantly higher in proliferative retinopathy compared with nonproliferative retinopathy. This specific subset of proteins was linked to inflammation, complement, and coagulation cascade proteins, protease inhibitors, apolipoproteins, immunoglobulins, and cellular adhesion molecules, reflecting the multifactorial nature of the disease. The identification of the key molecules of the disease is critical for the development of new therapeutic molecules and for the new use of existing drugs. Label free quantification