Relationship among VEGF, VEGF receptor, AGEs, and macrophages in proliferative diabetic retinopathy

Relationship among VEGF, VEGF receptor, AGEs, and macrophages in proliferative diabetic retinopathy
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DOI:
10.1016/j.diabres.2007.10.018
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发表时间:
2008-03-01
影响因子:
5.1
通讯作者:
Kanazawa, Yasunori
Kanazawa, Yasunori
中科院分区:
医学3区
文献类型:
--
作者:
Kakehashi, Akihiro;Inoda, Shigeru;Kanazawa, Yasunori

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目的:探讨血管内皮生长因子(VEGF)及其受体(flt-1)、糖基化(AGEs)在糖尿病肾病中的作用。方法:收集30例(增殖性糖尿病视网膜病变19眼,非糖尿病性眼病11眼)玻璃体手术患者的眼液、虹膜及新生血管膜标本。ELISA法检测眼液中VEGF和AGE的含量。对眼组织进行了VEGF、flt-1、AGES和巨噬细胞的免疫组织化学研究。结果:糖尿病患者玻璃体中平均VEGF和AGE水平(分别为695.7 pg/ml和2.4 mg/ml)明显高于非糖尿病患者(分别为25.9 pg/ml,p = 0.0007和1.3 mg/ml,p = 0.005)。同样,在房水中,糖尿病眼的VEGF和AGE水平显著高于非糖尿病眼。玻璃体和房水中的VEGF水平显著相关(r = 0.6; p = 0.02),但AGES不相关。房水和玻璃体中VEGF水平与AGE水平无相关性。在虹膜中,VEGF、AGES和巨噬细胞在糖尿病患者的标本中比非糖尿病患者的标本中染色更显著,而flt-1染色没有差异。新生血管膜染色更显着的所有(血管内皮生长因子,flt-1,AGES和巨噬细胞),甚至当与虹膜相比,从糖尿病患者diabetes.Conclusions:通过分析水和玻璃体液,增殖膜,虹膜从相同的患者,目前的临床研究强烈支持以前的报告,显示了血管内皮生长因子,巨噬细胞和AGES在糖尿病增殖性视网膜病变的发展中的作用。从目前的研究结果,我们表明,flt-1在视网膜新生血管膜的发展中起着重要的作用,但在虹膜和视网膜的作用是不确定的。(C)2007爱思唯尔爱尔兰有限公司保留所有权利。
Purpose: We studied the roles of vascular endothelial growth factor (VEGF), its receptor (flt-1), advanced glycation. end products (AGES), and macrophages in the development of proliferative diabetic retinopathy.Methods: Ocular fluid and small specimens of iris and neovascular membrane were obtained from 30 patients who underwent vitreous surgery (19 eyes with proliferative diabetic retinopathy [PDR], 11 eyes with non-diabetic ocular diseases). VEGF and AGE levels in ocular fluid were assayed by ELISA. Immunohistochemical studies of VEGF, flt-1, AGES, and macrophage were performed on the ocular tissues.Results: The mean VEGF and AGE levels in the vitreous (695.7 pg/ml and 2.4 mg/ml, respectively) were significantly higher in diabetic than in non-diabetic eyes (25.9 pg/ml, p = 0.0007 and 1.3 mg/ml, p = 0.005, respectively). Likewise, in the aqueous humor, VEGF and AGE levels were significantly higher in diabetic than in non-diabetic eyes. VEGF levels in the vitreous and aqueous humor were correlated significantly (r = 0.6; p = 0.02), but AGES were not. The VEGF levels were not correlated with AGE levels in the aqueous or vitreous. In the iris, VEGF, AGES, and macrophages were stained more prominently in the specimens from patients with diabetes than from patients without diabetes, while flt-1 staining did not differ. The Neovascular membranes were stained much more prominently for all (VEGF, flt-1, AGES and macrophages) even when compared with the iris from patients with diabetes.Conclusions: By analyzing aqueous and vitreous humor, proliferative membranes, and iris from the same patients, the current clinical study strongly supports previous reports that showed the role of VEGF, macrophages, and AGES in the development of diabetic proliferative retinopathy. From the results of the current study, we showed that flt-1 plays an important role in the development of retinal neovascular membranes but the role is uncertain in the iris and retina. (C) 2007 Elsevier Ireland Ltd. All rights reserved.