March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Optic Nerve Misprojections in the Zebrafish Mutant belladonna: A Disease Model for Infantile Nystagmus Syndrome
Author Affiliations & Notes
  • Sabina P. Huber-Reggi
    Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland
  • Chien-Cheng Chen
    Department of Neurology, University Hospital Zurich, Zurich, Switzerland
  • Lea Holliger
    Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland
  • Dominik Straumann
    Department of Neurology, University Hospital Zurich, Zurich, Switzerland
  • Stephan C. Neuhauss
    Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland
  • Melody Ying-Yu Huang
    Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland
    Department of Neurology, University Hospital Zurich, Zurich, Switzerland
  • Footnotes
    Commercial Relationships  Sabina P. Huber-Reggi, None; Chien-Cheng Chen, None; Lea Holliger, None; Dominik Straumann, None; Stephan C. Neuhauss, None; Melody Ying-Yu Huang, None
  • Footnotes
    Support  ZIHP
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 5604. doi:
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      Sabina P. Huber-Reggi, Chien-Cheng Chen, Lea Holliger, Dominik Straumann, Stephan C. Neuhauss, Melody Ying-Yu Huang; Optic Nerve Misprojections in the Zebrafish Mutant belladonna: A Disease Model for Infantile Nystagmus Syndrome. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5604.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Infantile nystagmus syndrome (INS) is a congenital ocular motor disorder characterized by involuntary conjugate horizontal oscillations of the eyes. INS is associated with reduced visual acuity. The etiology is still largely unknown, but misprojections of the optic nerve have been observed in some patients. Some individuals of the zebrafish belladonna (bel) mutant display a reversed optokinetic response (OKR) and spontaneous eye oscillations (SO) with waveforms essentially identical to INS when presented with a still grating. In bel optic nerve misprojection, including achiasmia, is often observed. In this study, we aimed to investigate how misprojections of the optic nerve are related to the ocular motor behavior in bel.

Methods: : OKR and SO were elicited in bel larvae using black-white gratings and subsequently the projection of the optic nerve was stained with fluorescent lipophilic dyes. Eye movements were recorded using a CCD camera, processed in real-time and analyzed offline. The extent of misprojections was extrapolated by signal intensity quantification on both brain sides and was correlated to the ocular motor phenotype.

Results: : The ocular motor behavior correlated with the retinofugal projection pattern. A normal ocular motor phenotype was observed in bel larvae with contralaterally projecting retinofugal fibers. The extent of misprojection was directly correlated to OKR efficiency with a reduction in larvae with few misprojecting retinal fibers and a reversal in larvae with a substantial amount of misprojecting retinal fibers. All larvae with reversed OKR displayed SO. Its frequency showed a positive correlation with the gain of the reversed OKR.

Conclusions: : The strong correlation between retinofugal projection patterns and ocularmotor behavior indicates that axon misrouting may be the cause for the observed ocular motor instabilities. We suggest that the misprojecting uncrossed fibers open the negative feedback loop regulating OKR into a positive loop, resulting in an increase in retinal slip that is triggering SO. Our work in zebrafish provides an animal model suggesting axon misrouting as an important contributing factor to eye oscillations in human INS.

Keywords: nystagmus • optic nerve • ocular motor control 
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