Host research mentor: Jill Helms, PhD, Professor of Surgery Stanford University
In humans, injuries to the retina can cause irreversible damage that results in vision impairment and blindness. The potential of stem cell-based treatments for these devastating conditions depends upon a detailed understanding of the growth factors and cytokines that maintain retinal homeostasis, and the roles they may play in activating retinal progenitor cells in the mammalian retina. Here, we demonstrate that potentiated Wnt signaling in the mammalian retina results in the increased production of retinal progenitor cells. Because the Wnt signal is transient, Axin2LacZ/LacZ retinal progenitor cells differentiate into Müller glia, interneurons, and photoreceptors. This leads to two distinct phenotypes: first, the intact Axin2LacZ/LacZ retina is hyper-cellular and contains more Müller glial cells and second, these Axin2LacZ/LacZ Müller glia give rise to more retinal progenitor cells after injury. The consequence of amplified Wnt signaling in the retina is a more robust reparative response. Given the highly conserved nature of the Wnt pathway in non-mammalian retinal regeneration, therapeutic strategies that exploit this unique property of the Wnt pathway may have therapeutic applications for neural injuries.