Speaker
Description
Synaptic pruning is a neurodevelopmental checkpoint that occurs to eliminate excess neurons and refine circuits in the nervous system. The retina consists of highly organised networks of neuronal and glial cells that connect to pass visual information. However, the cellular and molecular processes behind synaptic pruning in the retina remain unclear. Glial cells, like astrocytes, microglia and Müller glia (MG; the principal glia of the retina), contact neurons and synapses to provide a myriad of support functions. Microglia have long been thought to solely undertake retinal synapse pruning due to their widely reported role in the brain. Here, using fixed and live zebrafish retinas, we show that MG carry out phagocytosis of synapses, working alongside, but independently of microglia.
Pruning occurs in two distinct time points during development, with each glial cell type being the principal “pruner” at each stage. We conducted a molecular screen to investigate the molecular mechanisms that regulate these pruning events. We found that two signalling pathways belonging to the complement system, the classical and lectin complement pathways, are expressed in glia at the stages of pruning in the retina. Consistent with the brain, microglia act through the classical complement pathway, whilst MG mainly rely on the lectin system. We are now using CRISPR/Cas9 knockout and cell-specific over-expression to determine the role of these pathways in each glial cell during development. These findings provide new insights into the role of MG in retinal development and provide potential novel molecules to explore in promoting synaptic maintenance and support in ageing and neurodegenerative disease.
Lay Abstract
Synaptic pruning is a natural developmental process that removes extra neurons and refines nerve circuits in the nervous system. The retina is made of highly organised networks of nerve and support cells that pass visual information. However, the exact cellular and molecular processes behind retinal pruning remain unclear.
Support cells called glia, including astrocytes, microglia, and Müller glia (MG, the main glial cells in the retina), interact with nerves and help support them in a myriad of ways. Microglia were thought to be the only cells that remove connections in the retina, owing to their well-known role in the brain. Using zebrafish retinas, we found that MG also remove connections, working alongside, but independently of microglia.
We found that these cells use specific immune signals to guide pruning. Microglia primarily use one system (the classical complement pathway), whereas MG rely on a different one (the lectin complement pathway). We are now using advanced genetic tools to test how turning these pathways on or off affects pruning.
These discoveries show that MG play a larger role in shaping the retina and could help develop ways to protect or restore retinal connections, potentially preventing vision loss in ageing or eye diseases.
| Lay Title | Muller Glia: Shaping how the eye connects |
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| Role | PhD Student |