Chemokines in proliferative diabetic retinopathy and proliferative vitreoretinopathy

Chemokines in proliferative diabetic retinopathy and proliferative vitreoretinopathy
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DOI:
10.1684/ecn.2006.0033
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发表时间:
2006-09-01
影响因子:
2.8
通讯作者:
Van Damme, Jo
Van Damme, Jo
中科院分区:
医学4区
文献类型:
--
作者:
Abu El-Asrar, Ahmed M.;Struyf, Sofie;Van Damme, Jo

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目的。目的:检测增殖性糖尿病视网膜病变(PDR)、增殖性玻璃体视网膜病变(PVR)和孔源性视网膜脱离(RD)患者玻璃体和血清中趋化因子CCL1/I-309、CCL2/MCP-1、CCL3/MIP-1α、CCL4/MIP-1β、CCL7/MCP-3、CCL8/MCP-2、CXCL5/ENA-78、CXCL6/GCP-2、CXCL10/IP-10和CXCL11/I-TAC的表达,探讨MCP-1、CX12/SDF-1和趋化因子受体CXCR3在视网膜上皮细胞中的表达。方法:研究方法。玻璃体切除手术患者的玻璃体体液和血清样本用于治疗RD(57例)、PVR(32例)和PDR(88例)。采用酶联免疫吸附试验检测趋化因子水平。应用免疫组织化学技术对18例PDR膜和5例PVR膜进行了研究。结果。在所有研究的趋化因子中,只有MCP-1和IP-10在玻璃体液样本中检测到。玻璃体液样本中单核细胞趋化蛋白-1水平显著高于血清样本(p<0.001)。增生性玻璃体增生症和增生性增生性玻璃体视网膜病变患者的玻璃体标本中单核细胞趋化蛋白-1水平显著高于增生性视网膜病变患者(p=0.0002)。活动期PDR患者玻璃体液中单核细胞趋化蛋白-1水平显著高于非活动期患者(P=0.0224)。玻璃体液标本中IP-10水平显著高于血清标本(p=0.0035)。增生性玻璃体增生症和增生性增生性玻璃体视网膜病变患者的玻璃体标本中IP-10水平显著高于增生性视网膜病变患者(p=0.0083)。增殖性视网膜病变活动期患者玻璃体标本中IP-10阳性率明显高于非活动期患者(p=0.0214)。在所有患者以及RD和PDR患者的玻璃体液样本中,IP-10检测的发生率与单核细胞趋化蛋白-1水平的升高之间存在显著的相关性(P<所有比较均为0.001)。MCP-1和SDF-1定位于肌成纤维细胞、PVR和PDR膜以及PDR膜中的血管内皮细胞。PDR膜血管内皮细胞表达CXCR3。结论。MCP-1、IP-10和SDF-1可能参与了PVR和PDR的发病过程。肌成纤维细胞和血管内皮细胞是视网膜前膜表达MCP-1、SDF-1和CXCR3的主要细胞类型。
Purpose. To determine levels of the chemokines CCL1/I-309, CCL2/MCP-1, CCL3/MIP-1 alpha, CCL4/MIP-1 beta, CCL7/MCP-3, CCL8/MCP-2, CXCL5/ENA-78, CXCL6/GCP-2, CXCL10/IP-10, and CXCL11/I-TAC in the vitreous humor and serum, from patients with proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), and rhegmatogenous retinal detachment with no PVR (RD), and to investigate the expression of MCP-1, CXCL12/SDF-1, and the chemokine receptor CXCR3 in epiretinal membranes. Methods. Paired vitreous humor and serum samples were obtained from patients undergoing vitrectomy for the treatment of RD (57 specimens), PVR (32 specimens), and PDR (88 specimens). The levels of chemokines were measured by enzyme-linked immunosorbent assays. Eighteen PDR and 5 PVR membranes were studied by immunohistochemical techniques. Results. Of all the chemokines studied, only MCP-1 and IP-10 were detected in vitreous humor samples. MCP-1 levels in vitreous humor samples were significantly higher than in serum samples (p < 0.001). MCP-1 levels were significantly higher in vitreous humor samples from patients with PVR and PDR compared with RD (p=0.0002). MCP-1 levels in vitreous humor samples from patients with active PDR were significantly higher than in inactive PDR cases (p=0.0224). IP-10 levels in vitreous humor samples were significantly higher than in serum samples (p=0.0035). IP-10 levels were significantly higher in vitreous humor samples from patients with PVR and PDR compared with RD (p=0.0083). The incidence of IP-10 detection in vitreous humor samples was significantly higher in active PDR cases compared with inactive cases (p=0.0214). There was a significant association between the incidence of IP-10 detection and increased levels of MCP-1 in vitreous humor samples from all patients, and patients with RD and PDR (p < 0.001 for all comparisons). MCP-1, and SDF-1 were localized in myofibroblasts; in PVR and PDR membranes and in vascular endothelial cells in PDR membranes. CXCR3 was expressed by vascular endothelial cells in PDR membranes. Conclusion. MCP-1, IP-10 and SDF-1 may participate in pathogenesis of PVR and PDR. Myofibroblasts and vascular endothelial cells are the major cell types expressing MCP-1, SDF-1, and CXCR3 in epiretinal membranes.