Abstract
Infantile nystagmus is a debilitating involuntary eye movement disorder often associated with retinal diseases such as congenital stationary night blindness (CSNB). The oscillating eye movements of infantile nystagmus come with reduced visual acuity and strongly impair quality of life. No cure exists for this condition. Previously, we demonstrated that nystagmus in the CSNB mouse model
Nyx
nob
has a retinal cause. Specifically, we found that synchronized oscillations of retinal ganglion cells (RGCs) are transmitted to the accessory optic system, triggering compensatory eye movements. The RGC oscillations appear to originate from a specific retinal cell type, the A
II
amacrine cell (A
II
AC), making these cells the preferred target for treatment. The reason for the oscillations in the A
II
ACs is not fully understood. Here, we found that pharmacologically activating the D1 dopaminergic receptors on the A
II
ACs in
Nyx
nob
mice down-regulated their voltage-gated sodium and potassium channels, leading to a complete suppression of the pathological oscillations of both A
II
ACs and RGCs. Furthermore, the signal fidelity of RGCs significantly improved due to the absence of the pathological oscillations. Our retinal network simulations confirm that the experimentally observed changes in properties of the A
II
AC voltage-gated currents are necessary and sufficient to account for the dopamine-dependent abolishment of these oscillations. Our findings provide a mechanistic understanding of dopaminergic regulation of A
II
ACs underlying infantile nystagmus.