Kjellström Ulrika, Kjellström Sten, Bruun Anitha, Andréasson Sten, Ponjavic Vesna
Dept. of Ophthalmology, University of Lund, Lund, S 221 85, Sweden.
Doc Ophthalmol. 2006 Jan;112(1):35-41. doi: 10.1007/s10633-006-0004-z.
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.
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.
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.
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.
我们之前报道了接受vigabatrin治疗的兔子视网膜功能和组织病理学的变化。本研究的目的是评估停止vigabatrin用药4 - 5个月后兔子的视网膜功能和视网膜组织病理学。
5只兔子在12 - 13个月期间每日口服vigabatrin。停止治疗后有4 - 5个月的观察期。6只饮用清水的兔子作为对照。每隔6 - 8周使用Burian - Allen双极接触镜进行标准化的全视野视网膜电图检查。18个月后处死兔子，研究切片视网膜的形态。用于染色的抗体有GABA、GFAP、GAD和波形蛋白。
治疗12 - 13个月后，所有接受vigabatrin治疗的兔子全视野视网膜电图均降低。治疗组动物与对照组之间暗适应视锥b波振幅存在统计学显著差异（Wilcoxon符号秩检验，p = 0.043）。停止治疗4 - 5个月后这种差异仍然存在。切片视网膜的免疫组织化学显示治疗组动物与对照组之间免疫反应性无显著差异。所有接受治疗的兔子在用药期间血清药物浓度均升高。
停止vigabatrin治疗4 - 5个月后，兔子全视野视网膜电图中孤立视锥b波振幅仍然降低，表明vigabatrin诱导的视网膜功能障碍可能是不可逆的。然而，未经治疗一段时间后免疫组织学正常，这意味着之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，可能仅在治疗期间存在。
