Boehm B O, Lang G, Feldmann B, Kurkhaus A, Rosinger S, Volpert O, Lang G K, Bouck N
Department of Internal Medicine, University of Ulm Medical School, Ulm, Germany.
Horm Metab Res. 2003 Jun;35(6):382-6. doi: 10.1055/s-2003-41362.
Retinopathy is the most common microvascular diabetes complication and represents a major threat to the eyesight. The aim of this study was to address the role of pro- and anti-angiogenic molecules in diabetic retinopathy in the aqueous humor of the eye. Aqueous humor was collected at cataract surgery from 19 diabetic patients and from 13 age- and sex-matched normoglycemic controls. Levels of pro-angiogenic vascular endothelial growth factor (VEGF) and angiogenic inhibitor pigment epithelium-derived factor (PEDF) were determined. Angiogenic activity of the aqueous humor was quantified by measuring its effect on the migration of capillary endothelial cells. In the aqueous fluid, VEGF levels were increased in diabetics (mean values: 501 vs. 367 pg/ml; p = 0.05), compared to controls. PEDF was found to be decreased in diabetics (mean values: 2080 vs. 5780 ng/ml; p = 0.04) compared to controls. In seven diabetic patients with proliferative retinopathy, the most profound finding was a significant decrease of the PEDF level (mean value: 237 ng/ml), whereas VEGF levels were comparable to diabetic patients without proliferation (mean value: 3153; p = 0.003). Angiogenic activity in samples of patients from the control group was generally inhibitory due to PEDF, and inhibition was blocked by neutralizing antibodies to PEDF. Likewise, in diabetics without proliferation, angiogenic activity was also blocked by antibodies to PEDF. We will demonstrate here that the level of the natural ocular anti-angiogenic agent PEDF is inversely associated with proliferative retinopathy. PEDF is an important negative regulator of angiogenic activity of aqueous humor. Our data may have implications for the development of novel regimens for diabetic retinopathy.
视网膜病变是糖尿病最常见的微血管并发症，对视力构成重大威胁。本研究的目的是探讨促血管生成分子和抗血管生成分子在糖尿病视网膜病变患者眼房水中的作用。在白内障手术时收集了19例糖尿病患者以及13例年龄和性别匹配的血糖正常对照者的房水。测定了促血管生成的血管内皮生长因子（VEGF）和血管生成抑制剂色素上皮衍生因子（PEDF）的水平。通过测量房水对毛细血管内皮细胞迁移的影响来量化其血管生成活性。与对照组相比，糖尿病患者房水中VEGF水平升高（平均值：501 vs. 367 pg/ml；p = 0.05）。与对照组相比，糖尿病患者房水中PEDF水平降低（平均值：2080 vs. 5780 ng/ml；p = 0.04）。在7例增殖性视网膜病变的糖尿病患者中，最显著的发现是PEDF水平显著降低（平均值：237 ng/ml），而VEGF水平与无增殖的糖尿病患者相当（平均值：3153；p = 0.003）。对照组患者样本中的血管生成活性通常因PEDF而受到抑制，并且这种抑制作用可被PEDF中和抗体阻断。同样，在无增殖的糖尿病患者中，血管生成活性也被PEDF抗体阻断。我们在此将证明，天然眼部抗血管生成剂PEDF的水平与增殖性视网膜病变呈负相关。PEDF是房水血管生成活性的重要负调节因子。我们的数据可能对糖尿病视网膜病变新治疗方案的开发具有启示意义。
