Expression profiles of cytokines and chemokines in vitreous fluid in diabetic retinopathy and central retinal vein occlusion

Expression profiles of cytokines and chemokines in vitreous fluid in diabetic retinopathy and central retinal vein occlusion
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DOI:
10.1007/s10384-011-0004-8
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发表时间:
2011-05-01
影响因子:
2.4
通讯作者:
Miyagawa, Yasuhiro
Miyagawa, Yasuhiro
中科院分区:
医学4区
文献类型:
--
作者:
Suzuki, Yukihiko;Nakazawa, Mitsuru;Miyagawa, Yasuhiro

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玻璃体液中细胞因子和趋化因子的参与在糖尿病视网膜病变(DR)和视网膜中央静脉阻塞(CRVO)的发生和发展中是重要的。本研究对76只增殖性DR合并糖尿病性黄斑水肿的患眼玻璃体液中细胞因子和趋化因子的浓度进行了检测和比较(DR组),10只眼CRVO(CRVO组)和23只眼视网膜前膜和黄斑裂孔(对照组),在玻璃体切除术期间从其收集玻璃体液样品的160只眼睛的系列中。在玻璃体切除术的初始阶段,使用玻璃体切割器通过抽吸收集玻璃体液样品。使用阵列系统同时测量27种不同的细胞因子和趋化因子(Bio-Rad(A(R)与珠粒组合的抗体(Bio-Rad),如下:白细胞介素(IL)-1 β,IL-1受体激动剂,IL-2,IL-4,IL-5,IL-6,IL-7,IL-8,IL-9,IL-10,IL-12,IL-13,IL-15,IL-17,嗜酸性粒细胞趋化因子,碱性成纤维细胞生长因子、粒细胞集落刺激因子(G-CSF)、粒细胞/巨噬细胞集落刺激因子(GM-CSF)、干扰素(IFN)-γ、干扰素诱导的10-kDa蛋白(IP-10)、单核细胞趋化蛋白-1(MCP-1)、巨噬细胞炎性蛋白-1 α(MIP-1 α)、MIP-1 β、血小板衍生生长因子(PDGF)-BB,活化后调节,正常T细胞表达和分泌,肿瘤坏死因子α与对照组相比,IL-6,IL-8,IL-10,IL-13,IP-10,MCP-1,MIP-1 β,DR组玻璃体液中的PDGF和VEGF显著较高,而CRVO组中的IL-1 β、IL-2、IL-5、IL-8、IL-9、IL-10、IL-12、IL-13、嗜酸性粒细胞趋化因子、G-CSF、IFN-γ、IP-10、MCP-1、MIP-1 β、TNF-α和VEGF的水平显著较高。CRVO组IL-2、IL-9、IL-12、MCP-1和IFN-γ水平较DR组明显升高。多因素回归分析显示,在DR组与VEGF相关的6个因子中,IL-10、IL-13与VEGF呈正相关,PDGF与VEGF呈负相关,除炎性细胞因子和神经营养因子VEGF外,抗炎性细胞因子IL-10、IL-13可能在DR和CRVO的发病机制中起重要作用;细胞因子和趋化因子也可能与玻璃体液中的VEGF相关。提示CRVO的炎症反应可能比DR更为活跃。
The involvement of cytokines and chemokines in vitreous fluid is important in the development and progression of diabetic retinopathy (DR) and central retinal vein occlusion (CRVO). In this study, the concentrations of cytokines and chemokines in the vitreous fluid of eyes with DR and CRVO were measured and compared.We studied 76 eyes with proliferative DR and diabetic macular edema (DR group), 10 eyes with CRVO (CRVO group), and 23 eyes with an epiretinal membrane and macular hole (control group), among a series of 160 eyes from which vitreous fluid samples were collected during vitrectomy. The vitreous fluid samples were collected by suction with a vitreous cutter at the initial stage of vitrectomy. Twenty-seven different cytokines and chemokines were measured simultaneously using an array system (Bio-Plex(A (R))) with beads combined with antibodies (Bio-Rad), as follows: interleukin (IL)-1 beta, IL-1 receptor agonist, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, eotaxin, basic fibroblast growth factor, granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-gamma, interferon-inducible 10-kDa protein (IP-10), monocytochemotactic protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, platelet-derived growth factor (PDGF)-BB, regulated upon activation, normal T cell expressed and secreted, tumor necrosis factor alpha (TNF-alpha), and vascular endothelial growth factor (VEGF).Compared to the control group, the levels of IL-6, IL-8, IL-10, IL-13, IP-10, MCP-1, MIP-1 beta, PDGF and VEGF in the vitreous fluid were significantly higher in the DR group, while the levels of IL-1 beta, IL-2, IL-5, IL-8, IL-9, IL-10, IL-12, IL-13, eotaxin, G-CSF, IFN-gamma, IP-10, MCP-1, MIP-1 beta, TNF-alpha and VEGF were significantly higher in the CRVO group. Compared to the DR group, IL-2, IL-9, IL-12, MCP-1 and IFN-gamma were significantly elevated in the CRVO group. Multivariate regression analysis revealed that among 6 factors correlated to VEGF in the DR group, IL-10 and IL-13 were more positively correlated and PDGF was most inversely correlated to VEGF.In addition to inflammatory cytokines and neurotrophic factors such as VEGF, anti-inflammatory cytokines such as IL-10 and IL-13 may be involved more in the pathogenesis of DR and CRVO than in other diseases; cytokines and chemokines may also be correlated to VEGF in the vitreous fluid. It is also suggested that the inflammatory reaction may be more activate in CRVO than in DR.