Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Sakyo, Kyoto, Japan.
Invest Ophthalmol Vis Sci. 2010 May;51(5):2347-55. doi: 10.1167/iovs.09-4158. Epub 2009 Dec 3.
To elucidate the effects of anecortave desacetate (AD) treatment on the kinetics of neovascular sprouting and its molecular mechanisms in retinal explants and during retinal vascular development in mice.
The antiangiogenic effects of AD on retinal angiogenesis were evaluated using two different models: a retinal explant model treated with vascular endothelial growth factor (VEGF) and a mouse model of postnatal retinal vascular development. Time-sequential observation was followed by the quantification of movements in neovascular sprouts and microglia. Real time-PCR was performed for the measurement of mRNA levels.
AD treatment significantly reduced the number of neovascular sprouts in retinal explants in a dose-dependent manner. Time-lapse imaging demonstrated that AD suppressed the new development and elongation of neovascular sprouts and the motility of tip cells. Moreover, AD treatment disturbed the filopodial extension and significantly decreased the transcriptional levels of KDR and platelet-derived growth factor-B, which are highly expressed in tip cells. In addition, it was confirmed that AD inhibited postnatal development of the retinal vasculature in mice, including filopodial extension in tip cells. These data suggest that AD suppresses both the development and the progression of sprouting angiogenesis. Interestingly, VEGF-induced microglial movements were also reduced in the retinal explants treated with AD. These changes were consistent with decreased mRNA levels of SDF-1 and Flt-1, which regulate the activation of inflammatory cells.
AD inhibited both the development and the progression of VEGF-induced retinal angiogenesis mediated, in part, by the suppression of tip cell motility in two angiogenic models.
阐明醋酸去氨加压素 (AD) 治疗对视网膜外植体中新血管芽生的动力学及其分子机制的影响及其在小鼠视网膜血管发育过程中的作用。
采用两种不同模型评估 AD 对视网膜血管生成的抗血管生成作用：一种是用血管内皮生长因子 (VEGF) 处理的视网膜外植体模型，另一种是小鼠出生后视网膜血管发育模型。通过对新血管芽生和小胶质细胞的运动进行时间序列观察来进行定量分析。Real time-PCR 用于测量 mRNA 水平。
AD 处理以剂量依赖性方式显著减少视网膜外植体中新血管芽生的数量。延时成像表明 AD 抑制了新血管芽生的新发育和伸长以及尖端细胞的运动。此外，AD 处理扰乱了丝状伪足的延伸，并显著降低了高度表达于尖端细胞的 KDR 和血小板衍生生长因子-B 的转录水平。此外，还证实 AD 抑制了小鼠视网膜血管的出生后发育，包括尖端细胞中的丝状伪足延伸。这些数据表明 AD 抑制了芽生血管生成的发育和进展。有趣的是，AD 处理的视网膜外植体中 VEGF 诱导的小胶质细胞运动也减少。这些变化与 SDF-1 和 Flt-1 的 mRNA 水平降低一致，后者调节炎症细胞的激活。
AD 通过抑制两种血管生成模型中尖端细胞运动，抑制了 VEGF 诱导的视网膜血管生成的发育和进展。
