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Safety of intravitreal bevacizumab in the developing rabbit retina.

机译:玻璃体内贝伐单抗在发育中的兔子视网膜中的安全性。

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PURPOSE: 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. METHODS: 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. RESULTS: The electroretinogram responses demonstrated normal retinal function in adult rabbits injected at postnatal age of 11 days to 25 days. Mean Vmax and sigma 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 Muller 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. CONCLUSION: 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.
机译:目的:目的是研究在成年白化病兔中,不同出生后注射玻璃体内单剂量贝伐单抗对视网膜功能和视网膜血管发育的长期影响。方法:将贝伐单抗注射至年龄在11天至25天的新生兔子的右眼,而每只兔子的左眼则注射相同体积的生理盐水作为对照。注射后1周和10周记录视网膜电图。注射后10周记录视觉诱发电位。在随访期结束时,处死兔子并准备视网膜以进行光学显微镜下的组织病理学研究,神经胶质原纤维酸性蛋白的免疫反应性以及减少形式的烟酰胺腺嘌呤二核苷酸磷酸黄递酶的组织化学,以评估视网膜的完整性。视网膜血管系统。结果:视网膜电图显示出生后11天至25天注射的成年兔视网膜功能正常。贝伐单抗注射后10周,每组兔子计算的平均Vmax和sigma值表明实验和对照组眼睛的视网膜功能相似。通过分别刺激每只眼睛记录的视觉诱发电位也相似。组织病理学研究得出相似的结果。与所有年龄组的兔子的对照眼相比,在实验眼中未观察到视网膜的结构性损伤,并且在实验眼中未观察到Muller细胞中神经胶质纤维酸性蛋白免疫反应性的增加。与所有年龄组的对照眼睛相比,烟酰胺腺嘌呤二核苷酸磷酸心肌黄递酶减少形式的血管染色显示,在实验眼中毛细血管网络的分支减少。结论:视网膜电图和形态学数据显示,在出生后前30天注射玻璃体内单剂量的贝伐单抗对成年兔感觉视网膜的结构和功能完整性没有有害影响。甚至在视网膜发育过程中使用贝伐单抗部分阻断血管内皮生长因子似乎也干扰了白化病兔视网膜血管系统的发育。但是,应谨慎地从兔子向人外推。

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