Endo M, Yanagisawa K, Tsuchida K, Okamoto T, Matsushita T, Higuchi M, Matsuda A, Takeuchi M, Makita Z, Koike T
Department of Internal Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
Horm Metab Res. 2001 May;33(5):317-22. doi: 10.1055/s-2001-15122.
Clinical studies have shown a relationship between diabetic retinopathy and vascular endothelial growth factor (VEGF) levels in ocular fluid. Advanced glycation end products (AGEs) have been implicated in diabetes complications, including diabetic retinopathy. Nepsilon-(carboxymethyl) lysine (CML) is a glycoxidation product that may be a marker of oxidative stress. In this study, we used enzyme-linked immunosorbent assays to determine the levels of VEGF, non-CML AGE and CML in the aqueous humor and serum of 82 Japanese patients with type 2 diabetes and 60 non-diabetic subjects. VEGF, non-CML AGE, and CML concentrations in aqueous humor and serum were then compared with the severity of diabetic retinopathy. Immunohistochemical detection analysis of non-CML AGE and CML was also performed using retinal tissues from patients with progressive diabetic retinopathy. Aqueous levels of VEGF, non-CML AGE and CML increased along with the progression of diabetic retinopathy compared to age-matched controls. After coagulation therapy, the VEGF, non-CML AGE, and CML levels were significantly reduced. Immunostaining showed diffuse co-localization of non-CML AGE and CML around microvessels and in the glial cells of proliferative membranes from patients with progressive diabetic retinopathy. These findings suggest that glycation and glycoxidation reactions (or oxidation, as revealed by CML) may contribute to both the onset and progression of diabetic retinopathy.
临床研究表明，糖尿病视网膜病变与眼内液中血管内皮生长因子（VEGF）水平之间存在关联。晚期糖基化终产物（AGEs）与糖尿病并发症有关，包括糖尿病视网膜病变。N-ε-（羧甲基）赖氨酸（CML）是一种糖氧化产物，可能是氧化应激的标志物。在本研究中，我们使用酶联免疫吸附测定法来测定82名日本2型糖尿病患者和60名非糖尿病受试者房水和血清中的VEGF、非CML AGE和CML水平。然后将房水和血清中的VEGF、非CML AGE和CML浓度与糖尿病视网膜病变的严重程度进行比较。还使用进展性糖尿病视网膜病变患者的视网膜组织进行了非CML AGE和CML的免疫组织化学检测分析。与年龄匹配的对照组相比，随着糖尿病视网膜病变的进展，房水中VEGF、非CML AGE和CML水平升高。凝固治疗后，VEGF、非CML AGE和CML水平显著降低。免疫染色显示，进展性糖尿病视网膜病变患者增殖膜的微血管周围和神经胶质细胞中，非CML AGE和CML呈弥漫性共定位。这些发现表明，糖基化和糖氧化反应（或如CML所示的氧化反应）可能在糖尿病视网膜病变的发生和进展中起作用。
