A Common Cause for Nystagmus in Different Congenital Stationary Night Blindness Mouse Models

Abstract

In Nyxnob mice, a model for congenital nystagmus associated with congenital stationary night blindness (CSNB), synchronous oscillating retinal ganglion cells (RGCs) lead to oscillatory eye movements, i.e., nystagmus. Given the distribution of mGluR6 and Cav1.4 in the retina as well as their clinical association with CSNB, we hypothesize that mGluR6-/- and Cav1.4-/- mutants show, like the Nyxnob mouse, oscillations that originate in the AII amacrine cells (AII ACs). Using eye movement and multi-electrode array (MEA) recordings of RGCs we show that the nystagmus as well as the underlying RGC oscillations are also present in mGluR6-/- and Cav1.4-/- mice. Yet, we find that the oscillations in the mGluR6-/- and Cav1.4-/- mutants slightly differ from each other and also from those of the Nyxnob mice. Moreover, each of the three mutations likely impacts the membrane potential of the AII ACs differently. Together our results indicate that nystagmus and oscillating RGCs are generalizable features associated with CSNB mutations localized at the photoreceptor-bipolar cell synapse.