Sugimoto S, Imawaka M, Kurata K, 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. 1996 Jun;21 Suppl 1:15-32. doi: 10.2131/jts.21.supplementi_15.
A procedure for recording the electroretinogram (ERG) in mice with a coiled stainless steel-type electrode was developed in order to examine retinal toxicity. Mice received a single i.v. of sodium iodate (SI), a retinotoxic compound, via the tail vein at a dose of 12.5, 25, or 50 mg/kg, and the ERG was recorded periodically for 28 days after dosing. In addition, the retina was examined histopathologically on day 30 after dosing. 1. The mice were anesthetized with mixed anesthetics of urethane, xylazine and ketamine after 30 to 60 min of dark-adaptation. Sixteen responses to repetitive 1.2 J light stimuli at a frequency of 0.2 or 0.1 Hz were averaged by a microcomputer. Body temperature of the mice was kept constant at 37 to 38 degrees C using a thermostatically controlled heating mat. Under these conditions, stable ERG a-wave, b-wave, oscillatory potentials and c-wave could be recorded for 28 days. 2. SI at doses of 25 mg/kg or more caused depression of the amplitudes of the oscillatory potentials, and enhancement of the a- and b-wave amplitudes, while the c-wave was already extinguished on day 1 after dosing. Following these changes, the amplitudes of the a- and b-wave decreased from day 3 or 7 after dosing. These changes did not recover until day 28 after dosing. 3. Upon histopathologic examination of the retina, folding of the outer nuclear layer, disarrangement of the rods and cones, decrease of the visual cells and swelling and decrease of the pigment epithelial cells were observed with SI at 25 mg/kg or more. 4. Using this recording technique, it was confirmed that a stable ERG was recorded repeatedly for 28 days in mice, and the effects of SI on the ERG could be detected. Histopathologic findings in the retina revealed the abnormal portions were correlated well with the changes in the ERG. These results indicate that the ERG recording procedure developed in this study is useful for evaluating retinal toxicity in mice.
为检测视网膜毒性,开发了一种使用盘绕式不锈钢型电极记录小鼠视网膜电图(ERG)的方法。小鼠通过尾静脉接受单次静脉注射碘酸钠(SI),这是一种视网膜毒性化合物,剂量分别为12.5、25或50 mg/kg,给药后定期记录28天的ERG。此外,在给药后第30天对视网膜进行组织病理学检查。1. 在暗适应30至60分钟后,用乌拉坦、赛拉嗪和氯胺酮的混合麻醉剂对小鼠进行麻醉。由微型计算机对频率为0.2或0.1 Hz的1.2 J重复光刺激的16次反应进行平均。使用恒温加热垫将小鼠体温保持在37至38摄氏度恒定。在这些条件下,可记录28天稳定的ERG a波、b波、振荡电位和c波。2. 25 mg/kg及以上剂量的SI导致振荡电位振幅降低,a波和b波振幅增强,而给药后第1天c波就已消失。在这些变化之后,给药后第3天或第7天a波和b波振幅开始下降。这些变化直到给药后第28天才恢复。3. 在对视网膜进行组织病理学检查时,观察到25 mg/kg及以上剂量的SI导致外核层折叠、视杆细胞和视锥细胞排列紊乱、视觉细胞减少以及色素上皮细胞肿胀和减少。4. 使用这种记录技术,证实了在小鼠中可重复记录28天稳定的ERG,并且可以检测到SI对ERG的影响。视网膜的组织病理学发现显示异常部位与ERG的变化密切相关。这些结果表明,本研究开发的ERG记录方法可用于评估小鼠的视网膜毒性。