Transgenic approach to reprogramming retinal glia to stem/progenitor cells
Loss of photoreceptor cells in inherited retinal degenerations and age-related macular degeneration accounts for 50% of all cases of blindness in Australia. During such degeneration processes, the Muller glia are known to undergo gliosis but have also been observed to undergo a partial reprogramming response to adopt a progenitor or stem cell-like phenotype. In fish, amphibians and to some extent birds, photoreceptors are able to regenerate following retinal injury; a phenomenon that is dependent on the reprogramming of glial cells (Müller cells). Recent data suggests that in mammalian retinae, Müller cells undergo partial reprogramming to a progenitor phenotype, expressing marker genes such as Pax6, Chx10 and nestin and have the potential to re-enter the cell cycle. Moreover, in vitro studies show that this can be augmented by Wnt/ß-catenin signaling. In this project, we aim to develop an in vivo model that permits specific targeting of Müller cells in the degenerating retina to conditionally activate Wnt signaling by genetic approaches. We hypothesize that activation of the Wnt pathway in Müller cells will initiate a cellular reprogramming response.
Techniques will include generation and management of transgenic mouse colonies, PCR genotyping, and examining the structure of the retina as well as key molecular markers by histology, RT-PCR, immunohistochemistry, western blotting and in situ hybridisation.
(collaboration with Fletcher Lab)
A/Prof Robb de Iongh
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School Research Themes
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