Mechanisms of Retinal Regeneration in Zebrafish
The zebrafish retina possesses the unique ability to repair and replace damaged cells. This is made possible through the regenerative properties of a resident adult stem cell in the retina, Müller glia, which reside in the inner nuclear layer of the retina. These cells are capable of dedifferentiation and the generation of proliferating progenitor cells. Previous studies in the Patton lab have demonstrated that inhibition of the neurotransmitter GABA can trigger regeneration in the retina of zebrafish. By intravitreal injection of the GABA antagonist, it was found that a regenerative response could be induced in undamaged eyes. Previous work also showed that the leptin receptor is required for initiation of retina regeneration. My focus is to determine the role of the leptin receptor when regeneration is initiated by inhibition of GABA. For this, I first identified a zebrafish line containing mutations in the leptin receptor with the goal to generate a homozygous mutant line. Moving forward, it is essential to be able to determine the fate of proliferating cells that are generated after injection of GABA. For this, I am developing a lineage tracing model in which cell specific expression of Cre recombinase can be used to effect a change in reporter expression as proliferating cells generated during regeneration differentiate into mature retinal cell types.