Shaping of Neuronal Connections by Resident Immune Cells

With this project, I aim to determine whether and how retinal microglia contribute to the development and regeneration of functional synaptic connections in the retina.

In late stages of age-related macular degeneration (AMD), light sensing cells (photoreceptors) in the eye die, leading to vision loss. To treat this with future approaches, we can potentially replace photoreceptors, but in order to work properly, these cells need to be able to communicate with other neurons in the eye that process light information and pass it to the brain. With this project, we will determine how microglia (immune cells of the eye) could help new photoreceptors establish connections with other neurons, potentially making future AMD treatments more effective.

There are two particularly unique aspects to this proposal. First, we will be able to observe live cell-cell interactions between neurons and microglia in living zebrafish larval retinas in the context of neuronal activity. Second, exploiting the endogenous regenerative capacity of the zebrafish retina, we will study the potential roles microglia play in synaptic rewiring of regenerated photoreceptors into existing retinal circuits after retinal damage.

Understanding how microglia assist in the development and regeneration of cone synapses will allow us to best support photoreceptor-replacement treatments for age-related macular degeneration by helping us identify microglial functions that must be preserved, directed, or mitigated to ensure the optimal integration and function of new photoreceptors in diseased retinas. This work will also reveal novel microglial functions in the retina as well as the mechanisms that underlie these functions.