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Mechanisms of rod photoreceptor motility in development and following transplantation

Aghaizu, ND; (2016) Mechanisms of rod photoreceptor motility in development and following transplantation. Doctoral thesis , UCL (University College London). Green open access

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Abstract

To establish the mature neuroepithelial tissue architecture, newborn neurons often migrate from their place of birth, usually at the apical neuroepithelial limit, towards their target destination. Even before neurons are born, the nucleus of the mitotic neuronal progenitor cell migrates within the apico-basal cellular extent in synchrony with the cell cycle (interkinetic nuclear migration or IKNM) – a migratory pattern so far only observed in mitotic epithelial progenitor cells. Rod photoreceptors, too, are born at the apical limit of the retinal neuroepithelium. They then populate a layer directly adjacent (outer nuclear layer or ONL), but not the more basal retinal layers. How rod photoreceptors become enriched specifically within the ONL is presently ill-defined. Here, it was identified that rod photoreceptor somata of the developing mouse retina are constantly pushed basally (presumably caused by proximal progenitor IKNM events). To become enriched apically within the (presumptive) ONL despite this, the post-mitotic rod photoreceptors utilised an IKNM-like migratory behaviour more typically associated with dividing cells: rod somata actively migrated apically, driven by microtubule-associated dynein I motors. Another microtubule-associated motor protein, KIF1A, acts as a molecular brake during basal displacement, preventing ectopic basal positions. Rod somata oscillate between apical and basal motions at least from P1 up until ~P10. Whether this involves a component of glial-guided migration could not be established beyond reasonable doubt. Nonetheless, this is the first report of an oscillatory, IKNM-like migration behaviour occurring within a post-mitotic neuronal cell population. Rod photoreceptors have also been assumed to migrate into the adult neural retina following sub-retinal transplantation for cell-replacement therapeutic purposes, although this has not been directly observed. Here, time-lapse footage for the first time showed rod photoreceptors migrating from the sub-retinal space into the host retina. This supports the notion that photoreceptor cell replacement therapy could become a clinically viable treatment option.

Type: Thesis (Doctoral)
Title: Mechanisms of rod photoreceptor motility in development and following transplantation
Event: University College London
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/1532694
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