Kakehashi Akihiro, Inoda Shigeru, Mameuda Chiho, Kuroki Masatoshi, Jono Tadashi, Nagai Ryuji, Horiuchi Seikoh, Kawakami Masanobu, Kanazawa Yasunori
Department of Ophthalmology, Saitama Medical Center, Jichi Medical University, Omiya, Japan.
Diabetes Res Clin Pract. 2008 Mar;79(3):438-45. doi: 10.1016/j.diabres.2007.10.018. Epub 2007 Nov 28.
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.
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.
The mean VEGF and AGE levels in the vitreous (695.7pg/ml and 2.4mg/ml, respectively) were significantly higher in diabetic than in non-diabetic eyes (25.9pg/ml, p=0.0007 and 1.3mg/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.
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.
我们研究了血管内皮生长因子（VEGF）及其受体（flt-1）、晚期糖基化终产物（AGEs）和巨噬细胞在增殖性糖尿病视网膜病变发展中的作用。
从30例行玻璃体手术的患者（19眼患有增殖性糖尿病视网膜病变[PDR]，11眼患有非糖尿病性眼部疾病）获取眼内液以及虹膜和新生血管膜的小标本。通过酶联免疫吸附测定法检测眼内液中的VEGF和AGE水平。对眼部组织进行VEGF、flt-1、AGEs和巨噬细胞的免疫组织化学研究。
糖尿病患者玻璃体中的VEGF和AGE平均水平（分别为695.7pg/ml和2.4mg/ml）显著高于非糖尿病患者（分别为25.9pg/ml，p = 0.0007和1.3mg/ml，p = 0.005）。同样，房水中，糖尿病患者的VEGF和AGE水平也显著高于非糖尿病患者。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。房水或玻璃体中的VEGF水平与AGE水平不相关。在虹膜中，糖尿病患者标本中的VEGF、AGEs和巨噬细胞染色比非糖尿病患者更明显，而flt-1染色无差异。即使与糖尿病患者的虹膜相比，新生血管膜对所有物质（VEGF、flt-1、AGEs和巨噬细胞）的染色也更明显。
通过分析同一患者的房水、玻璃体、增殖膜和虹膜，当前的临床研究有力地支持了先前的报告，即VEGF、巨噬细胞和AGEs在糖尿病增殖性视网膜病变发展中的作用。从当前研究结果来看，我们表明flt-1在视网膜新生血管膜的发展中起重要作用，但在虹膜和视网膜中的作用尚不确定。
