Department of Ophthalmology, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Retina. 2011 Oct;31(9):1885-95. doi: 10.1097/IAE.0b013e31821a88e2.
The purpose of this was to study the long-term effects of a single intravitreal dose of bevacizumab injected at different postnatal age on retinal function and development of retinal blood vessels in the adult albino rabbit.
Bevacizumab was injected into the right eye of newborn rabbits, aged 11 days to 25 days, whereas the left eye of each rabbit was injected with identical volume of saline and served as control. The electroretinogram was recorded 1 week and 10 weeks after injection. Visual evoked potentials were recorded 10 weeks after injection. At termination of the follow-up period, the rabbits were killed and the retinas were prepared for histopathologic studies at the light microscopic level, for glial fibrillary acidic protein immunoreactivity, and for reduced form of nicotinamide adenine dinucleotide phosphate diaphorase histochemistry to assess the integrity of the retinal vascular system.
The electroretinogram responses demonstrated normal retinal function in adult rabbits injected at postnatal age of 11 days to 25 days. Mean Vmax and σ values calculated for each group of rabbits, 10 weeks after bevacizumab injection, indicated similar retinal function of the experimental and control eyes. Visual evoked potentials recorded by stimulating each eye separately were also similar. The histopathologic studies yielded similar results; no structural retinal damage was observed in the experimental eyes compared with the control eyes of rabbits from all age groups, and no increased glial fibrillary acidic protein immunoreactivity in Müller cells was observed in the experimental eyes. Staining of blood vessels with reduced form of nicotinamide adenine dinucleotide phosphate diaphorase revealed decreased branching of the capillary network in the experimental eyes compared with the control eyes in all age groups.
The electroretinographic and morphologic data showed no deleterious effects of a single intravitreal dose of bevacizumab, injected during the first 30 days postnatally, on the structural and functional integrity of the sensory retina in the adult rabbit. Even partial blockage of vascular endothelial growth factor with bevacizumab applied during retinal development seems to interfere with the development of the retinal vascular system in the albino rabbit. However, extrapolation from rabbits to humans should be made with caution.
本研究旨在探讨新生兔不同日龄单次玻璃体内注射贝伐单抗对成年白化兔视网膜功能和血管发育的长期影响。
将贝伐单抗注射入 11 至 25 日龄新生兔右眼，左眼注射等量生理盐水作为对照。注射后 1 周和 10 周记录视网膜电图，10 周后记录视觉诱发电位。随访结束时处死动物，制备视网膜组织行光镜病理检查、胶质纤维酸性蛋白免疫组化及还原型烟酰胺腺嘌呤二核苷酸磷酸黄递酶组织化学染色，评估视网膜血管系统的完整性。
11 至 25 日龄新生兔注射贝伐单抗后成年兔视网膜电图反应正常。贝伐单抗注射后 10 周，各组兔 Vmax 和σ值计算表明实验眼和对照眼视网膜功能相似。分别刺激每只眼记录的视觉诱发电位也相似。光镜病理研究结果相似；与所有年龄组的对照眼相比，实验组眼未见结构视网膜损伤，实验组 Müller 细胞内胶质纤维酸性蛋白免疫反应性未见增加。用还原型烟酰胺腺嘌呤二核苷酸磷酸黄递酶染色血管显示实验组眼毛细血管网络分支较对照眼减少。
视网膜电图和形态学数据表明，新生兔出生后 30 天内单次玻璃体内注射贝伐单抗对成年兔感觉视网膜的结构和功能完整性无不良影响。即使在视网膜发育过程中应用贝伐单抗部分阻断血管内皮生长因子，似乎也会干扰白化兔视网膜血管系统的发育。但是，从兔子到人类的推断应该谨慎进行。
