Nystagmus in patients with congenital stationary night blindness (CSNB) originates from synchronously firing retinal ganglion cells.
Beerend H J Winkelman, Marcus H C Howlett, Maj-Britt Hölzel, Coen Joling, Kathryn H Fransen, Gobinda Pangeni, Sander Kamermans, Hiraki Sakuta, Masaharu Noda, Huibert J Simonsz, Maureen A McCall, Chris I De Zeeuw, Maarten Kamermans
Author Information
Beerend H J Winkelman: Netherlands Institute for Neuroscience, Amsterdam, the Netherlands. ORCID
Marcus H C Howlett: Netherlands Institute for Neuroscience, Amsterdam, the Netherlands. ORCID
Maj-Britt Hölzel: Netherlands Institute for Neuroscience, Amsterdam, the Netherlands.
Coen Joling: Netherlands Institute for Neuroscience, Amsterdam, the Netherlands.
Kathryn H Fransen: Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky, United States of America.
Gobinda Pangeni: Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky, United States of America.
Sander Kamermans: Polder Animation, Utrecht, the Netherlands. ORCID
Hiraki Sakuta: National Institute for Basic Biology, Okazaki, Japan.
Masaharu Noda: National Institute for Basic Biology, Okazaki, Japan.
Huibert J Simonsz: Netherlands Institute for Neuroscience, Amsterdam, the Netherlands. ORCID
Maureen A McCall: Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky, United States of America.
Chris I De Zeeuw: Netherlands Institute for Neuroscience, Amsterdam, the Netherlands.
Maarten Kamermans: Netherlands Institute for Neuroscience, Amsterdam, the Netherlands. ORCID
Congenital nystagmus, involuntary oscillating small eye movements, is commonly thought to originate from aberrant interactions between brainstem nuclei and foveal cortical pathways. Here, we investigated whether nystagmus associated with congenital stationary night blindness (CSNB) results from primary deficits in the retina. We found that CSNB patients as well as an animal model (nob mice), both of which lacked functional nyctalopin protein (NYX, nyx) in ON bipolar cells (BCs) at their synapse with photoreceptors, showed oscillating eye movements at a frequency of 4-7 Hz. nob ON direction-selective ganglion cells (DSGCs), which detect global motion and project to the accessory optic system (AOS), oscillated with the same frequency as their eyes. In the dark, individual ganglion cells (GCs) oscillated asynchronously, but their oscillations became synchronized by light stimulation. Likewise, both patient and nob mice oscillating eye movements were only present in the light when contrast was present. Retinal pharmacological and genetic manipulations that blocked nob GC oscillations also eliminated their oscillating eye movements, and retinal pharmacological manipulations that reduced the oscillation frequency of nob GCs also reduced the oscillation frequency of their eye movements. We conclude that, in nob mice, synchronized oscillations of retinal GCs, most likely the ON-DCGCs, cause nystagmus with properties similar to those associated with CSNB in humans. These results show that the nob mouse is the first animal model for a form of congenital nystagmus, paving the way for development of therapeutic strategies.
