Abstract
Purpose: :
Approximately 50% of the zebrafish mutant belladonna (bel) display a reversed optokinetic response (OKR) that has been associated with the failure of the retinal ganglion cells (RGC) to form an optic chiasm (Rick et al., 2000). We later observed another intriguing feature of these achiasmatic mutants: Spontaneous oscillatory eye movements. In this study, we set out to accurately describe the optokinetic abnormalities observed in these achiasmatic bel mutants. Furthermore, we tried to replicate the recorded eye movements in a quantitative model in order to confirm that the achiasmatic condition can be held responsible for the abnormal OKR.
Methods: :
The OKR was evoked with a computer–generated grating stimulus and captured by a CCD camera. The current angular eye position was derived by real–time image analysis. Custom–programmed software was used to smoothen the eye position trace, to eliminate saccade artifacts, and to perform statistical analysis. Finally, non–linear curve fitting techniques were applied to build a quantitative model in MATLAB Simulink.
Results: :
The reversed OKR was contrast sensitive, but only slightly stimulus velocity sensitive. When presented a still grating stimulus, some achiasmatic bel mutants exhibited spontaneous oscillatory eye movements that were contrast sensitive. The quantitative OKR model was built based on wild type eye behaviors. To mimic the achiasmatic bel mutants, we simply "rewired" the RGC to the ipsilateral hemisphere, thereby reversing the sign of the neural retinal slip velocity. In this way, we successfully reproduced the typical reversed OKR and the spontaneous oscillatory eye movements seen in achiasmatic bel mutants.
Conclusions: :
Based on the OKR data and with the support of our quantitative model, we hypothesize that both of these abnormal visual behaviors are mainly due to the misrouting of the RGC in the forebrain. Since humans with an achiasmatic condition or otherwise defective retinotectal projections often show a congenital nystagmus (CN), which closely resembles the spontaneous eye oscillations in the achiasmatic bel mutants, the data strongly imply a link between the unknown etiology of the CN and the underlying anatomical projection defect. Thus, the achiasmatic bel mutant is a valuable behavioral animal model for humans with CN and/or reversed OKR caused by the misrouting of the retinal fugal fibers.
Keywords: nystagmus • eye movements • visual impairment: neuro-ophthalmological disease