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血管内皮生长因子受体2抗体BC001减轻恒河猴(猕猴)激光诱导的脉络膜新生血管形成。

Vascular Endothelial Growth Factor Receptor 2 Antibody, BC001, Attenuates Laser-Induced Choroidal Neovascularization in Rhesus Monkeys (Macaca mulatta).

作者信息

Zhao Tao, Zhang Jie, Zhang Yanyan, Huang Jingjing, Wang Xin, Zhang Yingqian, Zhang Ming, Yuan Ye, Xiao Kai, Li Hongxia, Zhong Zhihui

机构信息

1 Shandong Buchang Pharmaceutical Company , Heze, China .

2 Laboratory of Nonhuman Primate Disease Modeling Research, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu, China .

出版信息

J Ocul Pharmacol Ther. 2015 Dec;31(10):611-6. doi: 10.1089/jop.2014.0148. Epub 2015 Sep 3.

Abstract

PURPOSE

A study was conducted to evaluate the inhibitory effects of vascular endothelial growth factor receptor 2 (VEGFR2) monoclonal antibody, BC001, against laser-induced choroidal neovascularization (CNV).

METHODS

We induced the experimental CNV in rhesus monkey eyes using laser photocoagulation. Monkeys were randomly assigned to 4 groups that received a single intravitreal administration of BC001 at 0 (vehicle-treated group), 0.05, 0.2, and 0.5 mg/eye. Fundus fluorescein angiography, optical coherence tomography, and histological studies were used for evaluations. The ocular recovery was determined by comparing changes of fluorescein leaking area and thickness of disrupted retina around the laser burn spot before and after drug administration. Choroidal blood vessels were stained and quantified by lectin staining. Hematoxylin and eosin staining was performed to determine the general histological complications.

RESULTS

An intravitreal injection of BC001 at 0.05, 0.2, and 0.5 mg per eye at 20 days after laser burn significantly reduced the CNV-induced fluorescein leakage, retina pathology, and aberrant choroidal vessel growth and did not change intraocular pressure or induce any immune response.

CONCLUSION

BC001 confers significant inhibitory effects against laser-induced CNV in rhesus monkeys, thereby suggesting that prevention of VEGFR2 activation may be promising as an alternative therapeutic target for exudative age-related macular degeneration.

摘要

目的

开展一项研究以评估血管内皮生长因子受体2(VEGFR2)单克隆抗体BC001对激光诱导的脉络膜新生血管(CNV)的抑制作用。

方法

我们使用激光光凝法在恒河猴眼中诱导实验性CNV。将猴子随机分为4组,分别在第0天(载体治疗组)、0.05、0.2和0.5mg/眼接受单次玻璃体内注射BC001。使用眼底荧光血管造影、光学相干断层扫描和组织学研究进行评估。通过比较给药前后激光灼伤部位周围荧光素渗漏面积和视网膜破坏厚度的变化来确定眼部恢复情况。通过凝集素染色对脉络膜血管进行染色和定量。进行苏木精和伊红染色以确定一般组织学并发症。

结果

在激光灼伤后20天,每只眼玻璃体内注射0.05、0.2和0.5mg的BC001可显著减少CNV诱导的荧光素渗漏、视网膜病变和异常脉络膜血管生长,且不改变眼压或诱导任何免疫反应。

结论

BC001对恒河猴激光诱导的CNV具有显著抑制作用,从而表明预防VEGFR2激活作为渗出性年龄相关性黄斑变性的替代治疗靶点可能具有前景。

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