| Summary: | Previous work by the group has determined that post-mitotic rod photoreceptor precursors, when transplanted into adult mouse retinae, possess the ability to migrate into the recipient retinal outer nuclear layer (ONL) where photoreceptors reside, assume mature rod morphologies and restore some visual function in models of blindness. This thesis focuses on the modes and kinetics of transplanted cell migration and comparison of migration and maturation of transplanted rods to the analogous processes during retinal development. To examine the kinetics of migration and maturation of transplanted rod precursors, recipient retinae were examined at a range of time-points post-surgery. Transplanted rods that had migrated into the ONL were counted and their maturation was analysed in terms of morphological differentiation, rod markers expression and maturation of the nuclear chromatin architecture. These events were compared to the analogous processes in normal retinal development. To further understand the migration ability of transplanted rod precursors, I investigated migration trends of the integration-competent cell population during development. A pulse-chase approach was used to gauge average changes in rod precursor position with time after cell cycle exit and the dynamics of migration were analysed through real-time imaging of explanted retinae. Both approaches indicated bidirectional trajectories of rod migration during development. A parallel focus has been testing of the hypothesis that transplanted rods use recipient Müller glial cells, which span the depth of the retina, as scaffolds along which to migrate. The spatial relationship between transplanted rods and recipient Müller cells was confirmed using nearest neighbour analysis. Through real-time in vitro imaging of rod-Müller cell co-cultures, rods could be observed to elongate and move in a directed manner along Müller cell surfaces.
|
|---|
