Nystagmus in patients with congenital stationary night blindness (CSNB) originates from synchronously firing retinal ganglion cells

Winkelman, Beerend H. J. and Howlett, Marcus H. C. and Hölzel, Maj-Britt and Joling, Coen and Fransen, Kathryn H. and Pangeni, Gobinda and Kamermans, Sander and Sakuta, Hiraki and Noda, Masaharu and Simonsz, Huibert J. and McCall, Maureen A. and De Zeeuw, Chris I. and Kamermans, Maarten and Demb, Jonathan (2019) Nystagmus in patients with congenital stationary night blindness (CSNB) originates from synchronously firing retinal ganglion cells. PLOS Biology, 17 (9). e3000174. ISSN 1545-7885

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Abstract

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.

Item Type: Article
Subjects: Research Scholar Guardian > Biological Science
Depositing User: Unnamed user with email support@scholarguardian.com
Date Deposited: 24 Jan 2023 08:07
Last Modified: 04 Sep 2023 11:49
URI: http://science.sdpublishers.org/id/eprint/65

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