Abu El-Asrar Ahmed M, Missotten Luc, Geboes Karel
Department of Ophthalmology, King Abdulaziz University Hospital, Airport Road, PO Box 245, Riyadh 11411, Saudi Arabia.
Br J Ophthalmol. 2007 Jun;91(6):822-6. doi: 10.1136/bjo.2006.109876. Epub 2007 Jan 17.
To investigate the expression of the hypoxia-inducible factor-1alpha (HIF-1alpha) and the protein products of its target genes vascular endothelial growth factor (VEGF), erythropoietin (Epo) and angiopoietins (Angs), and the antiangiogenic pigment epithelium-derived factor (PEDF) in proliferative diabetic retinopathy (PDR) epiretinal membranes.
Sixteen membranes were studied by immunohistochemical techniques.
Vascular endothelial cells expressed HIF-1alpha, Ang-2 and VEGF in 15 (93.75%), 6 (37.5%) and 9 (56.25%) membranes, respectively. There was no immunoreactivity for Epo, Ang-1 and PEDF. There were significant correlations between the number of blood vessels expressing the panendothelial marker CD34 and the numbers of blood vessels expressing HIF-1alpha (r = 0.554; p = 0.026), Ang-2 (r = 0.830; p<0.001) and VEGF (r = 0.743; p = 0.001). The numbers of blood vessels expressing Ang-2 and VEGF in active membranes were higher than that in inactive membranes (p = 0.015 and 0.028, respectively).
HIF-1alpha, Ang-2 and VEGF may play an important role in the pathogenesis of PDR. The findings suggest an adverse angiogenic milieu in PDR epiretinal membranes favouring aberrant neovascularisation and endothelial abnormalities.
研究缺氧诱导因子-1α(HIF-1α)及其靶基因血管内皮生长因子(VEGF)、促红细胞生成素(Epo)和血管生成素(Angs)的蛋白产物,以及抗血管生成的色素上皮衍生因子(PEDF)在增殖性糖尿病视网膜病变(PDR)视网膜前膜中的表达。
采用免疫组织化学技术研究16个视网膜前膜。
血管内皮细胞在15个(93.75%)、6个(37.5%)和9个(56.25%)视网膜前膜中分别表达HIF-1α、Ang-2和VEGF。Epo、Ang-1和PEDF无免疫反应性。表达全内皮标志物CD34的血管数量与表达HIF-1α(r = 0.554;p = 0.026)、Ang-2(r = 0.830;p<0.001)和VEGF(r = 0.743;p = 0.001)的血管数量之间存在显著相关性。活跃视网膜前膜中表达Ang-2和VEGF的血管数量高于不活跃视网膜前膜(分别为p = 0.015和0.028)。
HIF-1α、Ang-2和VEGF可能在PDR的发病机制中起重要作用。研究结果表明PDR视网膜前膜中存在不利的血管生成环境,有利于异常新生血管形成和内皮异常。