Lip P L, Chatterjee S, Caine G J, Hope-Ross M, Gibson J, Blann A D, Lip G Y H
University Department of Medicine, City Hospital, Birmingham B18 7QH, UK.
Br J Ophthalmol. 2004 Dec;88(12):1543-6. doi: 10.1136/bjo.2004.048587.
Proliferative diabetic retinopathy (PDR) may be a response to abnormal angiogenic growth factors such as vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), and the soluble angiopoietin receptor tie-2. The authors hypothesised the following: (a) there are differences in plasma levels of these growth factors in different grades of diabetic retinopathy; and (b) that the effects of intervention with panretinal laser photocoagulation (PRP) for PDR, and angiotensin receptor blockade (using eprosartan) for patients with other grades of diabetic retinopathy will be to reduce levels of the growth factors.
Cross sectional and interventional study (using PRP and eprosartan) in diabetic patients. VEGF, Ang-2, and tie-2 were measured by ELISA.
VEGF (p<0.001) and Ang-2 levels (p<0.001) were significantly higher in 93 diabetic patients compared to 20 healthy controls, with the highest levels in grade 2 and grade 3 diabetic retinopathy (p<0.05). Tie-2 was lower in diabetics compared to controls (p = 0.008), with no significant differences between the diabetic subgroups. Overall, VEGF significantly correlated with Ang-2 (p<0.001) and tie-2 (p = 0.004) but the correlation between Ang-2 and tie-2 levels was not significant (p = 0.065). Among diabetic patients only, VEGF levels were significantly correlated with Ang-2 (p<0.001) and tie-2 (p<0.001); the correlation between Ang-2 and tie-2 levels was also significant (p<0.001). There were no statistically significant effects of laser photocoagulation on plasma VEGF, Ang-2, and tie-2 in the 19 patients with PDR, or any effects of eprosartan in the 28 patients with non-proliferative diabetic retinopathy.
Increased plasma levels of VEGF and Ang-2, as well as lower soluble tie-2, were found in diabetic patients. The highest VEGF and Ang-2 levels were seen among patients with pre-proliferative and proliferative retinopathy, but there was no relation of tie-2 to the severity of retinopathy. As the majority of previous research into Ang-2 and tie-2 has been in relation to angiogenesis and malignancy, the present study would suggest that Ang-2 and tie-2 may be used as potential indices of angiogenesis in diabetes mellitus (in addition to VEGF) and may help elucidate the role of the angiopoietin/tie-2 system in this condition.
增殖性糖尿病视网膜病变（PDR）可能是对异常血管生成生长因子如血管内皮生长因子（VEGF）、血管生成素-2（Ang-2）和可溶性血管生成素受体tie-2的一种反应。作者提出以下假设：（a）这些生长因子的血浆水平在不同等级的糖尿病视网膜病变中存在差异；（b）对PDR进行全视网膜激光光凝（PRP）干预以及对其他等级糖尿病视网膜病变患者进行血管紧张素受体阻断（使用依普罗沙坦）的效果将是降低生长因子水平。
对糖尿病患者进行横断面和干预性研究（使用PRP和依普罗沙坦）。通过酶联免疫吸附测定法（ELISA）测量VEGF、Ang-2和tie-2。
与20名健康对照相比，93名糖尿病患者的VEGF（p<0.001）和Ang-2水平（p<0.001）显著更高，在2级和3级糖尿病视网膜病变中水平最高（p<0.05）。糖尿病患者的tie-2低于对照组（p = 0.008），糖尿病亚组之间无显著差异。总体而言，VEGF与Ang-2（p<0.001）和tie-2（p = 0.004）显著相关，但Ang-2和tie-2水平之间的相关性不显著（p = 0.065）。仅在糖尿病患者中，VEGF水平与Ang-2（p<0.001）和tie-2（p<0.001）显著相关；Ang-2和tie-2水平之间的相关性也显著（p<0.001）。在19名PDR患者中，激光光凝对血浆VEGF、Ang-2和tie-2没有统计学上的显著影响，在28名非增殖性糖尿病视网膜病变患者中，依普罗沙坦也没有任何影响。
在糖尿病患者中发现血浆VEGF和Ang-2水平升高，以及可溶性tie-2水平降低。在增殖前期和增殖性视网膜病变患者中观察到最高的VEGF和Ang-2水平，但tie-2与视网膜病变的严重程度无关。由于先前关于Ang-2和tie-2的大多数研究都与血管生成和恶性肿瘤有关，本研究表明Ang-2和tie-2可能（除VEGF外）用作糖尿病血管生成的潜在指标，并可能有助于阐明血管生成素/tie-2系统在这种情况下的作用。
