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Effect of Gabapentin/Memantine on the Infantile Nystagmus Syndrome in the Zebrafish Model: Implications for the Therapy of Ocular Motor Diseases.
Invest Ophthalmol Vis Sci. 2017 06 01; 58(7):3149-3157.IO

Abstract

Purpose

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.

Methods

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).

Results

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.

Conclusions

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.

Authors+Show Affiliations

Department of Neurology, University Hospital Zurich, University of Zurich, Switzerland.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28632848

Citation

Bögli, Stefan Yu, et al. "Effect of Gabapentin/Memantine On the Infantile Nystagmus Syndrome in the Zebrafish Model: Implications for the Therapy of Ocular Motor Diseases." Investigative Ophthalmology & Visual Science, vol. 58, no. 7, 2017, pp. 3149-3157.
Bögli SY, Afthinos M, Huang MY. Effect of Gabapentin/Memantine on the Infantile Nystagmus Syndrome in the Zebrafish Model: Implications for the Therapy of Ocular Motor Diseases. Invest Ophthalmol Vis Sci. 2017;58(7):3149-3157.
Bögli, S. Y., Afthinos, M., & Huang, M. Y. (2017). Effect of Gabapentin/Memantine on the Infantile Nystagmus Syndrome in the Zebrafish Model: Implications for the Therapy of Ocular Motor Diseases. Investigative Ophthalmology & Visual Science, 58(7), 3149-3157. https://doi.org/10.1167/iovs.16-21308
Bögli SY, Afthinos M, Huang MY. Effect of Gabapentin/Memantine On the Infantile Nystagmus Syndrome in the Zebrafish Model: Implications for the Therapy of Ocular Motor Diseases. Invest Ophthalmol Vis Sci. 2017 06 1;58(7):3149-3157. PubMed PMID: 28632848.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of Gabapentin/Memantine on the Infantile Nystagmus Syndrome in the Zebrafish Model: Implications for the Therapy of Ocular Motor Diseases. AU - Bögli,Stefan Yu, AU - Afthinos,Maresa, AU - Huang,Melody Ying-Yu, PY - 2017/6/21/entrez PY - 2017/6/21/pubmed PY - 2017/7/20/medline SP - 3149 EP - 3157 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 58 IS - 7 N2 - Purpose: 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. Methods: 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). Results: 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. Conclusions: 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. SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/28632848/Effect_of_Gabapentin/Memantine_on_the_Infantile_Nystagmus_Syndrome_in_the_Zebrafish_Model:_Implications_for_the_Therapy_of_Ocular_Motor_Diseases_ L2 - https://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.16-21308 DB - PRIME DP - Unbound Medicine ER -