Guerin Eoin, Sheridan Carl, Assheton David, Kent David, Wong David, Grant Maria, Hiscott Paul
Unit of Ophthalmology, Department of Clinical Sciences, UCD, Duncan Building, University of Liverpool, Daulby Street, Liverpool, L69 3GA, United Kingdom.
Microvasc Res. 2008 Apr;75(3):302-7. doi: 10.1016/j.mvr.2007.12.001. Epub 2007 Dec 23.
Endothelial progenitor cells (EPCs) have been shown to contribute to experimentally induced choroidal neovascularisation (CNV) in animal models. The recruitment pathway for EPCs is dependent on the chemokine stromal cell derived factor 1-alpha (SDF) and its receptor CXCR4 on the progenitor cell. We examined 23 specimens of CNV occurring secondary to a variety of aetiologies (10 secondary to age-related macular degeneration (AMD), 4 inflammatory, 4 idiopathic and 5 melanoma-associated) for the presence and distribution of SDF and CXCR4 in order to determine if this pathway may play a role in neovascularisation. Specimens were examined by immunohistochemistry using a panel of antibodies against SDF, CXCR4, vascular endothelial growth factor receptor 2 (VEGFR-2), CD34 (endothelial cells), CD68 (macrophages) and cytokeratins (retinal pigment epithelium; RPE). SDF was detected in 2 cases of CNV in AMD, 1 inflammatory CNV, 3 idiopathic CNVs and in 3 cases of CNV associated with melanoma. A significant association was found between SDF and VEGFR-2 immunostaining in individual membranes (p<0.001). Localisation of SDF immunostaining to the presumed RPE was also significant (p<0.05). CXCR4 immunostaining was widespread in all membranes in keeping with the published work of other investigators. Our study suggests that SDF, which may be produced by the RPE, could play a role in CNV.
内皮祖细胞(EPCs)已被证明在动物模型中可促进实验性诱导的脉络膜新生血管形成(CNV)。EPCs的募集途径依赖于趋化因子基质细胞衍生因子1α(SDF)及其在祖细胞上的受体CXCR4。我们检查了23份继发于多种病因的CNV标本(10份继发于年龄相关性黄斑变性(AMD),4份炎症性,4份特发性和5份黑色素瘤相关性),以确定SDF和CXCR4的存在及分布,从而判断该途径是否可能在新生血管形成中起作用。使用一组针对SDF、CXCR4、血管内皮生长因子受体2(VEGFR-2)、CD34(内皮细胞)、CD68(巨噬细胞)和细胞角蛋白(视网膜色素上皮;RPE)的抗体,通过免疫组织化学检查标本。在2例AMD的CNV、1例炎症性CNV、3例特发性CNV以及3例与黑色素瘤相关的CNV中检测到SDF。在单个膜中,SDF与VEGFR-2免疫染色之间存在显著相关性(p<0.001)。SDF免疫染色定位于推测的RPE也具有显著性(p<0.05)。与其他研究者已发表的工作一致,CXCR4免疫染色在所有膜中广泛存在。我们的研究表明,可能由RPE产生的SDF可能在CNV中起作用。