Sadamoto Kazuyo, Yamagiwa Yoshinori, Sakaki Hideyuki, Kurata Masaaki
Research & Development Division, Senju Pharmaceutical Co., Ltd., 1-5-4 Murotani, Nishiku, Kobe, Hyogo 651-2241, Japan.
J Vet Med Sci. 2018 Jun 6;80(6):901-908. doi: 10.1292/jvms.17-0613. Epub 2018 Apr 11.
In ophthalmological research, the use of zebrafish to investigate visual behaviors has been increasing, but can produce misleading, false-positive results if compounds adversely affect their motor functions or central nervous system. Therefore, histological analysis to identify a target organ is important in zebrafish toxicity assay. We investigated the retinal degeneration in zebrafish, using typical retinal toxicants, mainly sodium iodate and N-methyl-N-nitrosourea (MNU). No histopathological changes were found after sodium iodate exposure at 1.0 mM for 5 or 7 days in the retina of larval, juvenile, and adult zebrafish. There were also no obvious histopathological changes in the retina of adult zebrafish at 0.1 mM, even after 30 days treatment with sodium iodate. In addition, many proliferating cell nuclear antigen-positive cells were found not only in the ciliary marginal zone, but also in the outer nuclear layer, especially in larval and juvenile zebrafish with or without sodium iodate exposure. However, the concentrations of iodine in the blood and the eyeballs of adult zebrafish increased remarkably after the treatment. General retinal damage emerged after MNU exposure at 150 mg/l for 60 min in adult zebrafish, but first pyknotic cells appeared in the inner nuclear layer and the ganglion cell layer. Our findings indicate that zebrafish retina have a different reactivity pattern from mammalian animals against some retinal toxicants, and in them it is difficult to detect histopathological changes.
在眼科研究中,使用斑马鱼来研究视觉行为的情况日益增多,但如果化合物对其运动功能或中枢神经系统产生不利影响,可能会产生误导性的假阳性结果。因此,在斑马鱼毒性试验中,通过组织学分析来确定靶器官很重要。我们使用典型的视网膜毒物,主要是碘酸钠和N-甲基-N-亚硝基脲(MNU),研究了斑马鱼的视网膜退化情况。在幼虫、幼年和成年斑马鱼的视网膜中,1.0 mM碘酸钠暴露5天或7天后未发现组织病理学变化。即使在0.1 mM碘酸钠处理30天后,成年斑马鱼的视网膜也没有明显的组织病理学变化。此外,不仅在睫状边缘区,而且在外核层发现了许多增殖细胞核抗原阳性细胞,特别是在暴露或未暴露于碘酸钠的幼虫和幼年斑马鱼中。然而,处理后成年斑马鱼血液和眼球中的碘浓度显著增加。成年斑马鱼在150 mg/l MNU暴露60分钟后出现了一般性的视网膜损伤,但首先在内核层和神经节细胞层出现了固缩细胞。我们的研究结果表明,斑马鱼视网膜对某些视网膜毒物的反应模式与哺乳动物不同,并且在其中很难检测到组织病理学变化。