兔眼玻璃体腔注射抗血管内皮生长因子单克隆抗体Bevacizumab的视网膜毒性研究

目的观察不同剂量抗血管内皮生长因子单克隆抗体Bevacizumab兔眼玻璃体腔注射的视网膜毒性作用。方法16只新西兰无色素兔的32只眼随机分为药物注射组和对照组，药物注射组又根据玻璃体腔注射药物剂量不同分为A、B、C组，玻璃体腔注射Bevacizumab剂量分别为0.05、0.10、0.25 ml，分别含Bevacizumab 1.25、2.50、6.25 mg。对照组玻璃体腔注射0.9％生理盐水0.10 ml。注药后1、2、4周行视网膜电图（ERG）检查。另外 ，在兔眼玻璃体腔注射Bevacizumab后1、2、4周，每组各摘除2只兔眼，行视网膜组织形态及超 微结构的光学显微镜和透射电子显微镜观察。结果兔眼玻璃体腔注射 Bevacizumab后1、2、4周，兔眼ERG各项反应波形均正常，振幅均未出现异常改变（P＞0.05）。光学显微镜下观察 ，药物注射组和对照组视网膜各层组织形态在各时间点均未见异常。透射电子显微镜观察， A、B组与对照组无明显差异；C组视网膜光感受器细胞出现部分线粒体损伤，发生肿胀和积 水变，4周时病变无缓解。结论单次兔眼玻璃体腔注射Bevacizumab 1.25 mg或2.50 mg是安全的。（中华眼底病杂志，2008，24：193-196）

Retinal toxicity study of jntravitreal bevacizumab in albino rabbit

Objective To observe the retinal toxicity of intravitreal injection of Bevacizumab (Avastin)in albino rabbit eyes at different doses. Methods Sixteen New Zealand albino rabbits,thirtytwo eyes were divided into four groups at random.Three groups were prepared for Avastin experiment,named A,B,C.Each group received intravitreal injection of Avastin at dose 1.25 mg/0.05 ml,2.5 mg/0.1 ml and 6.25 mg/0.25 m1 respectively.The other group named D served as a control,and accepted intravitreal injection of 0.9%normal saline 0.1 ml.Then test it by electroretinagram(ERG)after 1,2 and 4 weeks.In addition,each group was removing two rabbit's eyes to observe the retinal morphology and ultrastructure by light microscope and transmission electron microscopy after intravitreal injection avastin 1,2 and 4 weeks. Results The ERG pattern and amplitude of each group were normal after intravitreal injection Avastin 1,2 and 4 weeks.(P＞0.05)Between study and control groups,there was no significant difference in retinal morphology which was observed by light microscope at any stage of the study.By electron microscopic observation,retinal ultramicrostructure was no evident retinal toxicity being tested both at group A and B(1.25 mg/0.05 ml and 2.5 mg/0.1 ml).But at group C (6.25 mg/0.25 ml),significant mitochondrial swelling and hydropic changes were seen in the inner segments of photoreceptors.And there was no improvement of the pathological changes in four weeks.Conclusion It is safe that intravitreal injection of Avastin in rabbit's eyes at dose 1.25 mg or 2.5 mg atsingle time.