Intercellular contact and cargo transfer between Müller glia and to microglia precede apoptotic cell clearance in the developing retina

Abstract

To clarify our understanding of glial phagocytosis in retinal development, we used real-time imaging of larval zebrafish to provide cell-type specific resolution of this process. We show that radial Muller glia frequently participate in microglial phagocytosis while also completing a subset of phagocytic events. Muller glia (MG) actively engage with dying cells through initial target cell contact and phagocytic cup formation after which an exchange of the dying cell from MG to microglia often takes place. Additionally, we find evidence that Muller glia cellular material, possibly from the initial Muller cells phagocytic cup, is internalized into microglial compartments. Previously undescribed Muller cell behaviors were seen, including cargo splitting, wrestling for targets, lateral passing of cargo to neighbors, and engulfment of what is possibly synaptic puncta. Collectively, our work provides new insight into glial functions and intercellular interactions, which will allow future work to understand these behaviors on a molecular level. Summary StatementReal-time imaging of developing zebrafish retinas reveals intercellular exchanges between Muller glial cells and to microglia during the clearance of apoptotic cells.