Sugimoto S, Imawaka M, Imai R, Kanamaru K, Ito T, Sasaki S, Ando T, Saijo T, Sato S
Drug Safety Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
J Toxicol Sci. 1997 Nov;22 Suppl 2:315-25. doi: 10.2131/jts.22.supplementii_315.
A procedure for recording the electroretinogram (ERG) in pigmented mice, C57BL, based on the ERG recording technique reported previously in albino mice, ICR, and giving careful consideration to the influence of anesthetics and dark-adaptation, was developed in order to examine retinal toxicity. Pigmented mice were given a single i.v. injection of monoiodoacetic acid (IAA), a known retinotoxic compound, via a tail vein at a dose of 30, 45 or 60 mg/kg, and the ERG was recorded periodically over the next 14 days. In addition, the retinas were examined histopathologically on day 15. The results were as follows. 1. The oscillatory potentials were not distinct in the ERGs from mice anesthetized with pentobarbital as compared to the ERGs from non-anesthetized mice. ERG waveforms obtained from mice anesthetized with a mixture of urethane, xylazine and ketamine or xylazine and ketamine were almost the same as those obtained from non-anesthetized mice. Therefore, the ERGs were recorded under mixed anesthesia, ketamine and xylazine, in the following study. Stable ERGs could be recorded after 40 min of dark-adaptation. 2. IAA at doses of 30 and 45 mg/kg caused slight depression of the amplitudes of the a-, b- and c-waves; however, these changes were no longer observed 7 days after dosing. At a dose of 60 mg/kg, the ERG waves were markedly depressed 1 day after dosing, and recovery was not observed until day 14. 3. Upon histopathologic examination of the retinas, a remarkable decrease in visual cells and thinning of the rod and cone layers and outer plexiform layer were observed with IAA at a dose of 60 mg/kg. 4. Using this newly developed recording technique, it was confirmed that stable ERGs could be recorded from pigmented mice repeatedly for 14 days, and the effects of IAA on the ERG could be detected. Histopathological abnormalities in the retinas correlated well with the changes in the ERGs. These results indicate that the newly developed ERG recording procedure is useful for evaluating retinal toxicity in pigmented mice.
基于之前报道的ICR白化小鼠视网膜电图（ERG）记录技术，并充分考虑麻醉剂和暗适应的影响，开发了一种在C57BL有色小鼠中记录ERG的方法，以检测视网膜毒性。给有色小鼠经尾静脉单次静脉注射已知的视网膜毒性化合物一碘乙酸（IAA），剂量为30、45或60mg/kg，并在接下来的14天内定期记录ERG。此外，在第15天对视网膜进行组织病理学检查。结果如下：1.与未麻醉小鼠的ERG相比，戊巴比妥麻醉小鼠的ERG中振荡电位不明显。用乌拉坦、赛拉嗪和氯胺酮或赛拉嗪和氯胺酮混合麻醉的小鼠获得的ERG波形与未麻醉小鼠获得的波形几乎相同。因此，在以下研究中，在氯胺酮和赛拉嗪混合麻醉下记录ERG。暗适应40分钟后可记录到稳定的ERG。2.30和45mg/kg剂量的IAA导致a波、b波和c波振幅略有降低；然而，给药7天后这些变化不再出现。在60mg/kg剂量下，给药1天后ERG波明显降低，直到第14天才观察到恢复。3.在视网膜组织病理学检查中，60mg/kg剂量的IAA导致视细胞显著减少，杆体和锥体层以及外网状层变薄。4.使用这种新开发的记录技术，证实了可以从有色小鼠中反复记录14天的稳定ERG，并且可以检测到IAA对ERG的影响。视网膜中的组织病理学异常与ERG的变化密切相关。这些结果表明，新开发的ERG记录程序可用于评估有色小鼠的视网膜毒性。
