Imai R, Sugimoto S, Ando T, Sato S
Research and Development Division, Hikari Branch, Takeda Chemical Industries, Ltd., Yamaguchi, Japan.
J Toxicol Sci. 1990 Nov;15(4):263-74. doi: 10.2131/jts.15.263.
A procedure for recording the electroretinogram (ERG) and the visual evoked potential (VEP) in freely moving cats was developed and used to test the visual toxicity of nalidixic acid. The electrodes for recording the ERG and VEP were implanted chronically in the sclera of the eye and on the surface of the visual cortex, respectively. Both the ERG and VEP were simultaneously recorded in freely moving cats using a slip ring that allows the cat to move freely without twisting the cables. After a 15-min dark-adaptation period, 20 responses to repetitive photic stimulation with an intensity of 2 joules and a 10-sec interstimulus interval were averaged by means of a minicomputer. The waveform of the ERG consisted of a negative wave (a-wave) followed by a positive wave (b-wave) with 2 to 3 oscillatory potentials on the rising slope. The VEP consisted of initial positive wave (P1 wave) followed by a negative wave (N1 wave) and late positive and negative deflections. The amplitude of the components of the ERG and VEP varied considerably from animal to animal, whereas within the same animal they were very stable. Using this technique, the effects of nalidixic acid, a retinotoxic compound, on the ERG and VEP were studied. Nalidixic acid produced a marked, but transient, decrease in the amplitude of the ERG b-wave after a single intravenous injection at a dose of 10 mg/kg. After repeated doses at 40 mg/kg/day for 2 weeks, the reduction in the amplitude of the b-wave was stronger, but remained transient. Upon ophthalmologic and histopathologic examination of the retina, no abnormalities indicating visual toxicity were observed. These results indicate that this procedure for recording the ERG and VEP is useful for evaluating the visual toxicity of drugs in freely moving cats.
我们开发了一种在自由活动的猫身上记录视网膜电图(ERG)和视觉诱发电位(VEP)的方法,并用于测试萘啶酸的视觉毒性。记录ERG和VEP的电极分别长期植入眼睛的巩膜和视觉皮层表面。使用滑环在自由活动的猫身上同时记录ERG和VEP,该滑环可使猫自由移动而不会扭绞电缆。在15分钟的暗适应期后,通过小型计算机对强度为2焦耳、刺激间隔为10秒的重复光刺激的20次反应进行平均。ERG的波形由一个负波(a波)后跟一个正波(b波)组成,在上升斜率上有2至3个振荡电位。VEP由初始正波(P1波)后跟一个负波(N1波)以及晚期正负偏转组成。ERG和VEP各成分的幅度在不同动物之间差异很大,而在同一动物体内它们非常稳定。使用该技术,研究了具有视网膜毒性的化合物萘啶酸对ERG和VEP的影响。萘啶酸以10mg/kg的剂量单次静脉注射后,ERG的b波幅度出现明显但短暂的下降。以40mg/kg/天的剂量重复给药2周后,b波幅度的降低更强,但仍为短暂性。对视网膜进行眼科和组织病理学检查,未观察到表明视觉毒性的异常情况。这些结果表明,这种记录ERG和VEP的方法可用于评估自由活动猫中药物的视觉毒性。