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玻璃体内注射贝伐单抗和雷珠单抗在脉络膜新生血管大鼠模型中是否有效?

Are intravitreal bevacizumab and ranibizumab effective in a rat model of choroidal neovascularization?

作者信息

Lu Fang, Adelman Ron A

机构信息

Department of Ophthalmology and Visual Science, Yale University, School of Medicine, 40 Temple Street, Suite 3D, New Haven, CT 06510, USA.

出版信息

Graefes Arch Clin Exp Ophthalmol. 2009 Feb;247(2):171-7. doi: 10.1007/s00417-008-0936-y. Epub 2008 Sep 10.

Abstract

BACKGROUND

Vascular endothelial growth factor (VEGF) is an important stimulator of choroidal neovascularization (CNV). Bevacizumab (Avastin), ranibizumab (Lucentis) and pegaptanib sodium (Macugen) are anti-VEGF medications that have been used in the treatment of CNV. The purpose of our study is to evaluate the efficacy and safety of intravitreal injections of bevacizumab, ranibizumab and pegaptanib sodium in the treatment of CNV in a rat model.

METHODS

Multiple CNV lesions were induced by laser photocoagulation of the retina in Brown-Norway rats. After 3 weeks, 17 rats were divided into three groups and received intravitreal injections of bevacizumab, ranibizumab or pegaptanib sodium in different dosages. The lesions were evaluated by fluorescein angiography 1, 7, 14, and 28 days later to assess the efficacy of these medications.

RESULTS

Different doses of bevacizumab did not show any effect on stopping the leakage on fluorescein angiography on days 1, 7, 14, and 28. Ranibizumab and pegaptanib sodium did not stop the leakage of CNV either. No angiographic or histopathologic toxicity was observed.

CONCLUSIONS

These three anti-VEGF agents did not show any therapeutic effect on stopping CNV leakage in rats. Previous experiments with ranibizumab in monkeys resulted in a significant decrease in leakage of CNV. The difference may be due to the fact that both ranibizumab and bevacizumab are humanized and species-specific. There are several studies evaluating the effect of bevacizumab in non-primates. Since bevacizumab is humanized, the results of studies on non-primates may not be similar to humans and non-human primates.

摘要

背景

血管内皮生长因子(VEGF)是脉络膜新生血管形成(CNV)的重要刺激因子。贝伐单抗(阿瓦斯汀)、雷珠单抗(Lucentis)和培加他尼钠(Macugen)是已用于治疗CNV的抗VEGF药物。我们研究的目的是评估玻璃体内注射贝伐单抗、雷珠单抗和培加他尼钠治疗大鼠模型中CNV的疗效和安全性。

方法

通过对棕色挪威大鼠视网膜进行激光光凝诱导多个CNV病变。3周后,将17只大鼠分为三组,分别接受不同剂量的玻璃体内注射贝伐单抗、雷珠单抗或培加他尼钠。在1、7、14和28天后通过荧光素血管造影评估病变,以评估这些药物的疗效。

结果

不同剂量的贝伐单抗在第1、7、14和28天对荧光素血管造影上的渗漏停止均未显示任何效果。雷珠单抗和培加他尼钠也未阻止CNV的渗漏。未观察到血管造影或组织病理学毒性。

结论

这三种抗VEGF药物在阻止大鼠CNV渗漏方面未显示出任何治疗效果。先前在猴子身上进行的雷珠单抗实验导致CNV渗漏显著减少。差异可能是由于雷珠单抗和贝伐单抗都是人源化且具有物种特异性。有几项研究评估了贝伐单抗在非灵长类动物中的作用。由于贝伐单抗是人源化的,在非灵长类动物上的研究结果可能与人类和非人灵长类动物不同。

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