Bögli Stefan Yu, Afthinos Maresa, Huang Melody Ying-Yu
Department of Neurology, University Hospital Zurich, University of Zurich, Switzerland.
Department of Neurology, University Hospital Zurich, University of Zurich, Switzerland 2Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Switzerland 3Neuroscience Center Zurich (ZNZ), University of Zurich and ETH Zurich, Switzerland.
Invest Ophthalmol Vis Sci. 2017 Jun 1;58(7):3149-3157. doi: 10.1167/iovs.16-21308.
Infantile nystagmus syndrome (INS) is a disorder characterized by typical horizontal eye oscillations. Due to the uncertain etiology of INS, developing specific treatments remains difficult. Single reports demonstrated, on limited measures, alleviating effects of gabapentin and memantine. In the current study, we employed the zebrafish INS model belladonna (bel) to conduct an in-depth study of how gabapentin and memantine interventions alleviate INS signs, which may further restore visual conditions in affected subjects. Moreover, we described the influence of both medications on ocular motor functions in healthy zebrafish, evaluating possible iatrogenic effects.
Ocular motor function and INS characteristics were assessed by eliciting optokinetic response, spontaneous nystagmus, and spontaneous saccades in light and in dark, in 5- to 6-day postfertilization bel larvae and heterozygous siblings. Single larvae were recorded before and after a 1-hour drug treatment (200 mM gabapentin/0.2 mM memantine).
Both interventions significantly reduced nystagmus intensity (gabapentin: 59.98%, memantine: 39.59%). However, while the application of gabapentin affected all tested ocular motor functions, memantine specifically reduced nystagmus amplitude and intensity, and thus left controls completely unaffected. Finally, both drug treatments resulted in specific changes in nystagmus waveform and velocity.
Our study provides deeper insight into gabapentin and memantine treatment effect in the zebrafish INS model. Moreover, this study should establish zebrafish as a pharmacologic animal model for treating nystagmus and ocular motor disease, serving as a basis for future large-scale drug screenings.
婴儿眼球震颤综合征（INS）是一种以典型水平眼球摆动为特征的疾病。由于INS的病因不明，开发特异性治疗方法仍然困难。单项报告显示，在有限的测量中，加巴喷丁和美金刚有缓解作用。在本研究中，我们采用斑马鱼INS模型颠茄（bel）深入研究加巴喷丁和美金刚干预如何减轻INS症状，这可能进一步恢复受影响个体的视力状况。此外，我们描述了两种药物对健康斑马鱼眼动功能的影响，评估可能的医源性效应。
在受精后5至6天的bel幼虫和杂合子同胞中，通过在明和暗条件下诱发视动反应、自发性眼球震颤和自发性扫视来评估眼动功能和INS特征。在1小时药物治疗（200 mM加巴喷丁/0.2 mM美金刚）前后记录单个幼虫的情况。
两种干预均显著降低了眼球震颤强度（加巴喷丁：59.98%，美金刚：39.59%）。然而，虽然加巴喷丁的应用影响了所有测试的眼动功能，但美金刚特异性地降低了眼球震颤的幅度和强度，因此对对照组完全没有影响。最后，两种药物治疗均导致眼球震颤波形和速度发生特异性变化。
我们的研究更深入地了解了加巴喷丁和美金刚在斑马鱼INS模型中的治疗效果。此外，本研究应将斑马鱼确立为治疗眼球震颤和眼动疾病的药理学动物模型，为未来大规模药物筛选奠定基础。
