The retinal origin of congenital nystagmus.

TY - THES

T1 - The retinal origin of congenital nystagmus.

AU - Holzel, Maj-Britt

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

M3 - PhD thesis

ER -