Tyro3 is a key regulator of myelin structure and retinal function in the central nervous system

Background: While it is evident how critical myelin is for neural signalling in the CNS, the biological processes underpinning myelination remain unknown. Previously, we have shown that the receptor tyrosine kinase, Tyro3, regulates developmental myelination and myelin thickness in the CNS. Objectives: The aim of this study was to extend on our previous data by assessing the role of Tyro3 in regulating other myelin structures such as the node of Ranvier; and to assess the effect of Tyro3 loss on axonal conductivity and retinal function. Methods: To investigate node of Ranvier microstructure, we used electron microscopy and manually assessed paranodal loops. We measured nodal and paranodal widths using fluorescent immunohistochemistry staining and ImageJ software. To investigate neural conduction velocities, we measured visual evoked potentials in vivo and compound action potentials in slice cultures. Lastly, full-field electroretinograms and optical coherence tomographies were performed to assess retinal function. All experiments were wild-type to constitutive Tyro3 KO comparisons. Results: We show that Tyro3 receptor loss results in wider nodes of Ranvier and dysregular paranodal loop attachment at nodes. KO mice did not show significant alterations to axonal conduction in visual evoked potentials but did have reduced response amplitudes in compound action potentials. Finally, we show that Tyro3 loss results in a decrease in signal output from photoreceptor, bipolar and particularly retinal ganglion cells. Conclusion: Signalling via Tyro3 is key for the attachment of paranodal loops at nodes of Ranvier. Tyro3 deficient myelin results in a decrease in neural response amplitude. Tyro3 is important for the function of photoreceptor, bipolar and retinal ganglion cells of the retina.