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贝伐单抗对离体脊椎动物视网膜功能的影响。

Effects of bevacizumab on retinal function in isolated vertebrate retina.

作者信息

Lüke M, Warga M, Ziemssen F, Gelisken F, Grisanti S, Schneider T, Lüke C, Partsch M, Bartz-Schmidt K U, Szurman P

机构信息

University Eye Hospital, Centre for Ophthalmology, Eberhard-KarlsUniversity of Tuebingen, Schleichstrasse 12-16, D-72076, Tuebingen, Germany.

出版信息

Br J Ophthalmol. 2006 Sep;90(9):1178-82. doi: 10.1136/bjo.2006.094995. Epub 2006 Jun 5.

Abstract

BACKGROUND

Bevacizumab (Avastin) is a recombinant protein that targets vascular endothelial growth factor (VEGF). In vitro, bevacizumab inhibits VEGF induced cell proliferation and tissue factor production. Abnormal angiogenesis involving VEGF is a central event during the development of choroidal neovascularisation (CNV). The present study was designed to evaluate the short term toxic effects of bevacizumab on retinal function for a therapeutic intraocular application.

METHODS

Isolated bovine retinas were perfused with an oxygen pre-incubated nutrient solution. The electroretinogram (ERG) was recorded as a transretinal potential using silver/silver chloride electrodes. Bevacizumab was added in different concentrations to the nutrient solution for 45 minutes. Thereafter the retina was reperfused for 60 minutes with normal nutrient solution. The percentage of a-wave and b-wave reduction during the application of bevacizumab was calculated and compared to control recordings.

RESULTS

During the application of three different concentrations of bevacizumab (0.08 mg/ml, 0.25 mg/ml, 0.8 mg/ml) no significant reduction of the a-wave and b-wave amplitude was observed. During the washout, the ERG amplitudes were unchanged.

CONCLUSION

The present study suggests that an intraocular application of 0.25 mg/ml bevacizumab for the treatment of CNV is reasonable. No significant short term effects of bevacizumab on retinal function were detected, but long term effects cannot be excluded.

摘要

背景

贝伐单抗(阿瓦斯汀)是一种靶向血管内皮生长因子(VEGF)的重组蛋白。在体外,贝伐单抗可抑制VEGF诱导的细胞增殖和组织因子生成。涉及VEGF的异常血管生成是脉络膜新生血管(CNV)形成过程中的核心事件。本研究旨在评估贝伐单抗眼内治疗应用对视网膜功能的短期毒性作用。

方法

将分离的牛视网膜用预充氧的营养液灌注。使用银/氯化银电极将视网膜电图(ERG)记录为跨视网膜电位。将不同浓度的贝伐单抗加入营养液中45分钟。此后,用正常营养液对视网膜再灌注60分钟。计算应用贝伐单抗期间a波和b波降低的百分比,并与对照记录进行比较。

结果

在应用三种不同浓度的贝伐单抗(0.08mg/ml、0.25mg/ml、0.8mg/ml)期间,未观察到a波和b波振幅有显著降低。在洗脱过程中,ERG振幅未发生变化。

结论

本研究表明,眼内应用0.25mg/ml贝伐单抗治疗CNV是合理的。未检测到贝伐单抗对视网膜功能有显著短期影响,但不能排除长期影响。

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