Sasaki Shoji, Yamashita Haruhiro, Yagi Kumiko, Iwaki Yoshinobu, Kimura Masaaki
Toxicology Laboratory, Medicinal Development Research Laboratories, Taisho Pharmaceutical Co., Ltd., 403 Yoshino-Cho 1, Kita-Ku, Saitama-Shi, Saitama 331-9530, Japan.
Toxicol Lett. 2006 Oct 10;166(2):115-21. doi: 10.1016/j.toxlet.2006.06.003. Epub 2006 Jun 16.
We investigated full-field ERGs in beagle dogs using a contact lens electrode with built-in LED. Experiment 1 was performed to determine the appropriate conditions for stimulus intensity and background illumination. We found that full-field ERGs could be recorded under the following conditions: stimulus intensity: -2.5logcds/m(2) in rod responses (RRs), 1.2logcds/m(2) in maximal responses (MRs), oscillatory potentials (OPs), cone responses (CRs), 30-Hz flicker responses (FRs), and background illumination: more than 25cd/m(2) in CRs and FRs. Experiment 2 was performed to apply full-field ERGs in beagle dogs to the detection of retinal toxicities. A dog was given one 30mg/kg dose of sodium iodate (NaIO(3)) intravenously. ERGs were recorded before administration and 1, 3, 5, 8, 24h, 7 and 14 days after administration of NaIO(3). The RRs disappeared completely at 1h when MRs and OPs decreased. On the other hand, CRs and FRs were recorded even at 8h. All responses disappeared at 24h. These findings indicate that retinal toxicity by NaIO(3) is first expressed in rods, followed by cones. These results suggest that full-field ERGs in beagle dogs using an LED contact lens can be used to evaluate toxic effects on rods and cones separately, with the potential to prove more useful than conventional methods for toxicological assessments of developing pharmaceuticals, and can be applied to it.
我们使用内置发光二极管的隐形眼镜电极,对比格犬进行了全视野视网膜电图(ERG)研究。实验1旨在确定刺激强度和背景照明的合适条件。我们发现,在以下条件下可记录到全视野ERG:刺激强度:视杆细胞反应(RRs)为-2.5logcds/m²,最大反应(MRs)、振荡电位(OPs)、视锥细胞反应(CRs)、30赫兹闪烁反应(FRs)为1.2logcds/m²;背景照明:CRs和FRs中超过25cd/m²。实验2将比格犬的全视野ERG应用于视网膜毒性检测。给一只狗静脉注射一剂30mg/kg的碘酸钠(NaIO₃)。在注射NaIO₃前以及注射后1、3、5、8、24小时、7天和14天记录ERG。RRs在1小时时完全消失,此时MRs和OPs下降。另一方面,CRs和FRs甚至在8小时时仍可记录到。所有反应在24小时时消失。这些发现表明,NaIO₃引起的视网膜毒性首先表现在视杆细胞,随后是视锥细胞。这些结果表明,使用发光二极管隐形眼镜对比格犬进行全视野ERG可分别用于评估对视杆细胞和视锥细胞的毒性作用,有可能比传统方法在开发药物的毒理学评估中更有用,并可应用于该评估。