Cell Lineage Tracing Neurotransmitter Inhibited Retina Regeneration
These studies traced the cell-lineage of proliferating cells in the retinas of zebrafish to determine how these cells differentiate and develop after the initial proliferation stage. These studies are based on past research which has shown that the Muller glia (MG) in zebrafish retinas have a robust regenerative response to perturbations in neurotransmission. Zebrafish have similar retinal architecture to mammals, such as both containing photoreceptors, which release glutamate onto horizontal cells, which in turn may release gaba onto MG. Under situations in which the release of glutamate is inhibited, either through damage to the photoreceptors or through drug induced inhibition, the Muller glia are activated and dedifferentiate and produce progenitor cells. In humans and other mammals, these MG also proliferate in response to injury through gliosis (Ramachandran et al, 2010). However, these proliferating cells are not dedifferentiated so they can not regenerate the damaged cells and so vision can not be regained, but instead undergo hypertrophy. Past experiments in the Patton lab have shown that using the drug gabazine to block gaba neurotransmission downstream of photoreceptors causes a similar response as physical injury. Using a specific double transgenic fish line, gabazine was used to generate proliferative cells that will switch from MCherry to GFP permanently for identification as newly generated cells. These GFP positive proliferative response cells were tested using antibodies for different retinal cell types to follow their differentiation. Determining the cell fate of these new cells may provide some insight into how gaba inhibition stimulates MG proliferation.