[A procedure for electroretinogram (ERG) recording in mice--effect of monoiodoacetic acid on the ERG in pigmented mice].
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.
Sugimoto
S
S
Drug Safety Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Imawaka
M
M
Imai
R
R
Kanamaru
K
K
Ito
T
T
Sasaki
S
S
Ando
T
T
Saijo
T
T
Sato
S
S
D000758:Anesthesia; D019162:Anesthetics, Combined / Q000494:pharmacology; D000818:Animals; D003623:Dark Adaptation / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography / Q000187:drug effects / Q000379:methods*; D005069:Evaluation Studies as Topic; D007461:Iodoacetates / Q000633:toxicity*; D019807:Iodoacetic Acid; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D014991:Xylazine / Q000494:pharmacology
D019162:Anesthetics, Combined; D007461:Iodoacetates; D014991:Xylazine; D007649:Ketamine; D019807:Iodoacetic Acid