兔眼玻璃体腔注射抗血管内皮生长因子单克隆抗体Bevacizumab的毒性观察

Toxicity observation of intravireal injection of bevacizumab in rabbit eyes

目的观察不同剂量的抗血管内皮生长因子单克隆抗体Bevacizumab玻璃体腔注射后对兔眼角膜、房角、视网膜组织结构和功能的影响。方法24只健康新西兰大白兔分成3组，每组兔眼右眼分别注射Bevacizumab 1．25、2．50、5．00mg；左眼为对照眼，注射相同体积的0．9％生理盐水。注射药物前后裂隙灯显微镜及直接检眼镜检查眼前段和眼底，监测眼压。注药前以及注药后1、4、8周行闪光视网膜电图（ERG）检查。8周时行角膜内皮计数后，摘除眼球行光学显微镜及透射电子显微镜检查。结果3组兔眼注射药物前后各时间点眼压、角膜内皮计数、ERG的a、b波振幅差异无统计学意义（P〉0．05）。光学显微镜检查，3组兔眼角膜、房角、视网膜结构无明显变化。透射电子显微镜检查，视网膜超微结构亦无明显变化。结论玻璃体腔内注射1．25～5．00mg Bevacizumab对正常兔眼组织没有明显毒性。

Objective To observe the effects of structure and function of cornea, chamber angle and retina of varying doses of Bevacizumab which was injected intravitreally in rabbits. Methods Twenty-four New Zealand albino rabbits were divided into three groups randomly, the right eyes in three groups received intravitreal injection Avastin at dose 1.25 mg, 2.5 mg and 5 mg respectively as experimental eye, the left eyes accepted intravitreal injection 0. 9 % normal saline at the same volume as a control eye. The anterior segment of eye and ocular fundus were examined and intraocular pressure was measured by slit-lamp microscope and direct ophthalmoscope before and after injection. It was tested by Electroretinogram （ERG） before and after injection 1, 4, 8 weeks. At the 8th week, it carried out corneal endothelium counting; then enucleated eyes to observe by the light microscope and transmission electron microscope. Results No statistically significant difference regard to 10P,corneal endothelium counting, a- and b-waves of ERG at any stage of study in every group（P〉0.05）. No obvious change at cornea, chamber angle, retinal structure and retinal ultrastructure in every group under light microscope. Conclusion This study indicated that there is no obvious toxicity of intravitreal injection with Avastin 1.25-5.0 mg in normal rabbit eyes.