Division of Clinical Cell Therapy, Center for Advanced Medical Research and Development, Institute of Development, Aging, and Cancer, Tohoku University Graduate School of Medicine, Miyagi, Japan.
Invest Ophthalmol Vis Sci. 2011 May 17;52(6):3272-80. doi: 10.1167/iovs.10-6295.
PURPOSE. To determine the expression of vasohibin-1 during the development of experimentally induced choroidal neovascularization (CNV) and to investigate the effect of vasohibin-1 on the generation of CNV. METHODS. CNV lesions were induced in the eyes of wild-type (WT) and vasohibin-1 knockout (KO) mice by laser photocoagulation. The expression of vasohibin-1, vascular endothelial growth factor (VEGF), VEGF receptor-1 (VEGFR1), VEGFR2, and pigment epithelial-derived factor (PEDF) was determined by semiquantitative reverse transcription-polymerase chain reaction. The expression of vasohibin-1 was also examined by immunohistochemistry with anti-CD68, anti-alpha smooth muscle actin (αSMA), anti-cytokeratin, and anti-CD31. Vasohibin-1 was injected into the vitreous and the activity and size of the CNV were determined by fluorescein angiography and in choroidal flat mounts. RESULTS. Vasohibin-1 was detected not only in CD31-positive endothelial cells but also in CD68-positive macrophages and αSMA-positive retinal pigment epithelial cells. Strong vasohibin-1 expression was observed at day 28, when the CNV lesions had regressed by histologic examination. The vasohibin-1 level was significantly decreased at day 14 and increased at day 28 after laser application. Significantly less VEGFR2 expression was observed on day 4 after vasohibin-1. The expression of PEDF was not significantly changed by vasohibin-1 injection. Vasohibin-1 injection significantly suppressed the CNV, with no adverse side effects. The CNV lesions in the vasohibin-1-KO mice were significantly larger than those in the WT mice. CONCLUSIONS. The endogenous expression of vasohibin-1 is associated with the natural course of the development of CNV. Intravitreal injections of vasohibin-1 may be a method for inhibiting CNV.
目的。确定血管抑肽-1 在实验性诱导脉络膜新生血管（CNV）形成过程中的表达，并研究血管抑肽-1 对 CNV 生成的影响。方法。通过激光光凝在野生型（WT）和血管抑肽-1 敲除（KO）小鼠的眼睛中诱导 CNV 病变。通过半定量逆转录聚合酶链反应测定血管抑肽-1、血管内皮生长因子（VEGF）、VEGF 受体-1（VEGFR1）、VEGFR2 和色素上皮衍生因子（PEDF）的表达。通过免疫组织化学用抗 CD68、抗α平滑肌肌动蛋白（αSMA）、抗细胞角蛋白和抗 CD31 检测血管抑肽-1 的表达。将血管抑肽-1 注入玻璃体，并通过荧光素血管造影和脉络膜平面铺片确定 CNV 的活性和大小。结果。血管抑肽-1 不仅在 CD31 阳性的内皮细胞中检测到，而且在 CD68 阳性的巨噬细胞和 αSMA 阳性的视网膜色素上皮细胞中也检测到。在组织学检查显示 CNV 病变消退的第 28 天观察到强烈的血管抑肽-1 表达。在激光应用后第 14 天和第 28 天，血管抑肽-1 水平显著降低。在血管抑肽-1 后第 4 天观察到 VEGFR2 表达明显减少。血管抑肽-1 注射对 PEDF 的表达没有明显影响。血管抑肽-1 注射显著抑制 CNV，无不良反应。血管抑肽-1-KO 小鼠的 CNV 病变明显大于 WT 小鼠。结论。内源性血管抑肽-1 的表达与 CNV 发展的自然过程有关。玻璃体内注射血管抑肽-1 可能是抑制 CNV 的一种方法。
