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Retinal Function in Rabbits Does Not Improve 4–5 Months after Terminating Treatment with Vigabatrin

机译:Vigabatrin终止治疗后4-5个月,兔子的视网膜功能没有改善

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Purpose: We have previously reported changes in retinal function and histopathology in rabbits treated with vigabatrin. The purpose of the present study was to evaluate retinal function and histopathology of retina in rabbits 4–5 months after terminating vigabatrin medication. Methods: Five rabbits were treated with a daily per oral dose of vigabatrin during 12–13 months. After terminating treatment an observation period of 4–5 months followed. Six rabbits receiving water served as controls. Standardized full-field electroretinograms were performed every 6–8 weeks, using a Burian–Allen bipolar contact lens. After 18 months the rabbits were sacrificed and the morphology of the sectioned retina was studied. The antibodies used for staining were GABA, GFAP, GAD, and vimentin. Results: After 12–13 months of treatment the full-field ERG was reduced in all rabbits treated with vigabatrin. There was a statistically significant difference in the dark adapted cone b-wave amplitude between treated animals and controls (Wilcoxon signed-rank test, p = 0.043). This difference was consistent also 4–5 months after terminating treatment. Immunohistology of the sectioned retina demonstrated no significant difference in immunoreactivity between treated animals and controls. All treated rabbits demonstrated elevated serum concentration of the drug during medication. Conclusion: Four to five months after terminating treatment with vigabatrin the rabbit full-field ERG remains reduced in isolated cone b-wave amplitude indicating that vigabatrin induced retinal dysfunction may be irreversible. However, immunohistology is normal after a period without treatment, implying that the previously described changes in retinal morphology and glial cell activity are reversible, and probably exist only during treatment.
机译:目的:我们先前已经报道了用维加巴特林治疗的兔子的视网膜功能和组织病理学变化。本研究的目的是评估终止vigabatrin药物治疗后4-5个月的兔子的视网膜功能和视网膜组织病理学。方法:在12-13个月期间,每天口服5份维加巴特林治疗5只兔子。终止治疗后,观察期为4-5个月。接受水的六只兔子作为对照。使用Burian-Allen双极隐形眼镜每6-8周进行一次标准化的全场视网膜电图。 18个月后,处死兔子并研究视网膜切片的形态。用于染色的抗体是GABA,GFAP,GAD和波形蛋白。结果:经过12-13个月的治疗,所有接受vigabatrin治疗的兔子的全视野ERG均降低。在处理过的动物和对照组之间,暗适应锥B波振幅在统计学上有显着差异(Wilcoxon符号秩检验,p = 0.043)。终止治疗后4-5个月,这种差异也是一致的。视网膜切片的免疫组织学研究表明,治疗的动物与对照组之间的免疫反应性无显着差异。在治疗期间,所有治疗的兔子均表现出药物的血清浓度升高。结论:终止用vigabatrin治疗后的四到五个月,兔全视野ERG的孤立锥形b波振幅仍然降低,这表明vigabatrin引起的视网膜功能障碍可能是不可逆的。但是,未经治疗一段时间后,免疫组织学是正常的,这意味着先前描述的视网膜形态和神经胶质细胞活性的变化是可逆的,并且可能仅在治疗期间存在。

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