生长因子抑制剂贝伐单抗玻璃体腔注射对眼组织结构的影响

Changes in the histological structure of the eyes after injecting bevacizumab into the vitreous chamber

目的：贝伐单抗是一种基因工程的单克隆抗体，通过抑制血管内皮生长因子阻止新生血管的产生。玻璃体腔注射生长因子抑制剂是目前治疗新生血管性眼部疾病的最新手段。实验拟了解不同剂量贝伐单抗玻璃体腔注射对眼内组织结构和功能的近期影响，探讨安全剂量。方法：实验于2006-11／2007-05在山西医科大学完成。①实验材料：健康成年有色家兔32只，体质量2．0～3．0k，雌雄不拘。②分组处理：随机分为实验组24只和对照组8只。实验组动物右眼玻璃体腔分别注射不同剂量贝伐单抗（21，2．1，0．21g／L）0.2mL，每种剂量注射8只；对照组每只动物右眼玻璃体腔分别注射等量的平衡盐溶液。③评估：所有动物在注药前和注药后的第3，6，9，12，14天行眼压计、裂隙灯、眼底镜检查并拍摄眼底相片：注药前和注药后第7，14天行视网膜电图检查；第7，14天取眼球，在光学显微镜和透射电镜下观察视网膜组织结构变化。结果：32只家兔进入结果分析。①眼部组织结构变化：注药后21g／L组1只动物出现玻璃体混浊。②眼压变化：注药后第3天和第6天与注药前及注药后9，12，14d相比，眼压差别有显著性（P〈0.01）。③视网膜电图变化：有一定可逆性，21g／L组的b波下降幅度较其他组更明显。④光镜和电镜检测视网膜组织结构：具有一致性，对照组及2．1g/L组、0．21g／L组未见异常：21g/L组动物出现视网膜结构改变。结论：实验结果提示，玻璃体腔注射2．1g/L以下（含2．1g／L）贝伐单抗，在短期内对动物视网膜组织结构和神经传导功能无影响。

AIM： Bevacizumab is a kind of monoclonal antibody in genetic engineering. It prevents vascular endothelial growth factor from producing neonatal vessels. It＇s a new method to treat neonatal vascular ophthalmopathy through the injection of growth factor inhibitor into vitreous chamber at present. This study is designed to investigate the recent effect on the structure and function of intraocular tissues after different dosages of bevacizumab is injected into vitreous chamber, and to discuss how much amount is safe. METHODS： This experiment is performed from November 2006 to May 2007 in Shanxi Medical University. Materials： Thirty-two healthy adult pigmented rabbitsz weighed 2.0-3.0 kg, irrespective of gender, were adopted in this study.Grouping： Rabbits were at random divided into experimental group （n=24） and control group （n=8）. In the experimental group, each rabbit was respectively injected with 0.2 mL bevacizumab at different dosages （21, 2.1, 0.21 g/L） into right eye vitreous chamber, 8 animals at a dosage. In the control group, each rabbit＇s right eye vitreous chamber was injected with equal amount of balanced salt solution.Evaluation： Before injection, and at days 3, 6, 9. 12, 14 after injection, the ophthalmotonometer, slit-lamp and ophthalmoscope examinations were performed and pictures were taken for their eyeground. Before injection, at days 7 and 14 after injection, electroretinogram examination was performed; The eye-balls at days 7 and 14 were taken, and tissue structure of retina were observed under light microscope and transmission electron microscope. RESULTS： All 32 rabbits were involved in the result analysis. Vitreous opacity appeared in one animal 21 days after injection.There were significant differences in the intraocular pressure at days 3 and 6 after injection compared with before injection, and at days 9, 12, 14 after injection （P 〈 0.01）. Retinal electro-physiology showed certain reversibility, and b wave at day 21 after injection decreased more obviously than at other time points. The retinal structure by light microscope and electron microscope was the same. The abnormality was not found in control group, 2.1 g/L group and 0.21 g/L group. Animals in 21 g/L group appeared structure change in retinal physiology. CONCLUSION： Injection of bevacizumab below 2.1 g/L （including 2.1 g/L） into vitreous chamber has no obvious effect on animals＇ retinal tissue structure and the function of nerve conduction in the short term.