Tatar Olcay, Shinoda Kei, Adam Annemarie, Rohrbach Jens Martin, Lucke Klaus, Henke-Fahle Sigrid, Bartz-Schmidt Karl Ulrich, Grisanti Salvatore
University Eye Clinic at the Centre for Ophthalmology of the Eberhard-Karls-University Tübingen, Schleichstrasse 12-15, 72076 Tuebingen, Germany.
Exp Eye Res. 2006 Aug;83(2):329-38. doi: 10.1016/j.exer.2005.12.017. Epub 2006 Apr 11.
Endostatin is an endogenous angiogenesis inhibitor which requires E-selectin for its antiangiogenic activity. The aim of this study was to investigate the expression of endostatin in human choroidal neovascular membranes (CNV) secondary to age-related macular degeneration (AMD) with regard to vascularization and proliferative activity. An interventional case series of 36 patients who underwent removal of CNV were retrospectively investigated. Thirty-six CNV were analyzed by light microscopic immunohistochemistry for the expression of CD34 (endothelial cells, EC), CD105 (activated EC), Ki-67 (cell proliferation), Cytokeratin 18 (epithelial cells), VEGF (vascular endothelial growth factor), E-selectin and endostatin. Donor eyes (n=7) including one with AMD were used as controls. Endostatin immunoreactivity was present in choroidal vessels of five as well as in the retinal pigment epithelium (RPE)-Bruch's membrane complex of two donor eyes without AMD. In one eye with AMD, endostatin was detected in RPE, Bruch's membrane and choroidal vessels. Ninety-two percent (33/36) of CNV disclosed endostatin staining. RPE-Bruch's membrane complex, choroidal vessels and stroma were positive in 50% (18/36), 72% (26/36), and 78% (28/36) of the membranes, respectively. Both control eyes and CNV expressed all the investigated markers except E-selectin being positive only in membranes. Endostatin, an endogenous angiogenesis inhibitor, is expressed in CNV and its therapeutic up-regulation may be a new strategy in the treatment of neovascular AMD.
内皮抑素是一种内源性血管生成抑制剂,其抗血管生成活性需要E-选择素。本研究的目的是探讨内皮抑素在年龄相关性黄斑变性(AMD)继发的人脉络膜新生血管膜(CNV)中的表达与血管化和增殖活性的关系。对36例行CNV切除的患者进行了一项干预性病例系列的回顾性研究。通过光学显微镜免疫组织化学分析36个CNV中CD34(内皮细胞,EC)、CD105(活化的EC)、Ki-67(细胞增殖)、细胞角蛋白18(上皮细胞)、血管内皮生长因子(VEGF)、E-选择素和内皮抑素的表达。包括1只患有AMD的供体眼(n = 7)用作对照。在5只供体眼的脉络膜血管以及2只无AMD的供体眼的视网膜色素上皮(RPE)-布鲁赫膜复合体中存在内皮抑素免疫反应性。在1只患有AMD的眼中,在RPE、布鲁赫膜和脉络膜血管中检测到内皮抑素。92%(33/36)的CNV显示内皮抑素染色。RPE-布鲁赫膜复合体、脉络膜血管和基质分别在50%(18/36)、72%(26/36)和78%(28/36)的膜中呈阳性。对照眼和CNV均表达所有研究的标志物,但E-选择素仅在膜中呈阳性。内皮抑素作为一种内源性血管生成抑制剂,在CNV中表达,其治疗性上调可能是治疗新生血管性AMD的一种新策略。