PUBLICATION
Effect of Gabapentin/Memantine on the Infantile Nystagmus Syndrome in the Zebrafish Model: Implications for the Therapy of Ocular Motor Diseases
- Authors
- Bögli, S.Y., Afthinos, M., Huang, M.Y.
- ID
- ZDB-PUB-170622-7
- Date
- 2017
- Source
- Investigative ophthalmology & visual science 58: 3149-3157 (Journal)
- Registered Authors
- Bögli, Stefan, Huang, Melody Ying-Yu
- Keywords
- none
- MeSH Terms
-
- Amines/pharmacology*
- Animals
- Calcium Channel Blockers/pharmacology
- Cyclohexanecarboxylic Acids/pharmacology*
- Disease Models, Animal
- Excitatory Amino Acid Antagonists/pharmacology
- Eye Movements/drug effects
- Eye Movements/physiology*
- Memantine/pharmacology*
- Nystagmus, Congenital/drug therapy*
- Nystagmus, Congenital/physiopathology
- Syndrome
- Zebrafish
- gamma-Aminobutyric Acid/pharmacology*
- PubMed
- 28632848 Full text @ Invest. Ophthalmol. Vis. Sci.
Citation
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. 58:3149-3157.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping