- Author
-
M.-B. Hölzel
- Title
- The retinal origin of congenital nystagmus
- Supervisors
-
M. Kamermans
- Co-supervisors
-
M.H.C. Howlett
- Award date
- 1 May 2024
- Number of pages
- 153
- ISBN
- 9789464698190
- Document type
- PhD thesis
- Faculty
- Faculty of Medicine (AMC-UvA)
- Abstract
-
This thesis describes a revolutionary retinal mechanism leading to nystagmus in mouse models for CSNB. In patients with CSNB and nystagmus, mutations were found that are specifically present in the photoreceptor to ON-bipolar cell synapse, both pre- and postsynaptically. Here, we studied one presynaptic (Cav1.4) and two postsynaptic mutations (mGluR6nob3, Nyxnob) that cause CSNB. We found that all three mouse models show nystagmus and oscillating RGCs, but that they varied phenotypically between the three genotypes. All three mutations lead to an altered membrane potential of the ON-BCs and consequently of the AII ACs as well. The latter are then outside their normal working range and start to intrinsically oscillate. These oscillations are passed on to the RGCs, which also start to oscillate. This includes the ON-DSRGCs, that send an oscillatory retinal slip signal to the AOS, which consequently leads to compensatory, oscillatory eye movements, the nystagmus. The different phenotypes can thereby be explained by the difference in depolarization levels of the ON-BCs due to the different mutations.
- Persistent Identifier
- https://hdl.handle.net/11245.1/cc290215-0048-4f42-b80d-f76b407fa304
- Downloads
-
Thesis (complete)
Front matter
Chapter 1: General introduction
Chapter 2: Nystagmus in patients with congenital stationary night blindness (CSNB) originates from synchronously firing retinal ganglion cells
Chapter 3: A common cause for nystagmus in different congenital stationary night blindness mouse models
Chapter 4: Receptive field sizes of Nyxⁿᵒᵇ mouse retinal ganglion cells
Chapter 5: Reexpression of LRIT3 in rods is more effective in restoring the receptive field sizes than in cones of Lrit3-/- mice
Chapter 6: General discussion
Summary; Nederlandse samenvatting; PhD portfolio; List of publications; Curriculum vitae; Acknowledgements
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