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重复玻璃体内注射贝伐单抗和雷珠单抗在兔眼的安全性评价。

Safety evaluation of repeated intravitreal injections of bevacizumab and ranibizumab in rabbit eyes.

机构信息

Department of Ophthalmology, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

出版信息

Retina. 2010 Apr;30(4):671-81. doi: 10.1097/IAE.0b013e3181c0858c.

DOI:10.1097/IAE.0b013e3181c0858c
PMID:19952984
Abstract

PURPOSE

Repeated intravitreal injections of ranibizumab or bevacizumab are a common treatment for several retinal diseases. The aim of the present study was to evaluate the long-term retinal toxicity of repeated injections of ranibizumab and bevacizumab in rabbits.

METHODS

Albino rabbits were injected intravitreally with ranibizumab (1 mg/0.1 mL) or bevacizumab (2.5 mg/0.1 mL) into the right eye, whereas the left eye of each rabbit was injected with saline. Nine consecutive injections were administered at 14-day intervals. Electroretinographic responses and flash visual-evoked potentials were recorded periodically. After 18 weeks of follow-up, the rabbits were killed, and the retinas were prepared for morphologic examination and for immunocytochemistry for glial fibrillary acidic protein.

RESULTS

Electroretinographic and visual-evoked potential responses of the experimental and control eyes were similar in amplitude and pattern throughout the follow-up period. The histopathologic studies yielded similar results. No retinal damage was observed in the experimental and control eyes of all rabbits. Glial fibrillary acidic protein immunoreactivity showed staining only in retinal astrocytes but not in Müller cells in all rabbits.

CONCLUSION

The electrophysiological tests and the morphologic data indicate that the repeated intravitreal injections of ranibizumab or bevacizumab have no cumulative long-term toxic effect on the retina in rabbits.

摘要

目的

重复玻璃体内注射雷珠单抗或贝伐单抗是治疗几种视网膜疾病的常见方法。本研究旨在评估重复玻璃体内注射雷珠单抗和贝伐单抗对兔眼的长期视网膜毒性。

方法

白化兔右眼玻璃体内注射雷珠单抗(1mg/0.1mL)或贝伐单抗(2.5mg/0.1mL),左眼注射生理盐水。每隔 14 天连续注射 9 次。定期记录视网膜电图反应和闪光视觉诱发电位。随访 18 周后,处死兔子,制备视网膜进行形态学检查和胶质纤维酸性蛋白免疫细胞化学染色。

结果

在整个随访期间,实验组和对照组的眼电图和视觉诱发电位反应在振幅和模式上均相似。组织病理学研究也得出了相似的结果。所有兔子的实验组和对照组的眼睛均未观察到视网膜损伤。胶质纤维酸性蛋白免疫反应仅在所有兔子的视网膜星形胶质细胞中显示染色,而在 Müller 细胞中无染色。

结论

电生理测试和形态学数据表明,重复玻璃体内注射雷珠单抗或贝伐单抗对兔眼的视网膜没有累积的长期毒性作用。

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