Release of VAMP5-positive extracellular vesicles by retinal Muller glia in vivo

Cell-cell interactions in the central nervous system are based on the release of molecules mediating signal exchange and providing structural and trophic support through vesicular exocytosis and the formation of extracellular vesicles. The specific mechanisms employed by each cell type in the brain are incompletely understood. Here, we explored the means of communication used by Muller cells, a type of radial glial cells in the retina, which forms part of the central nervous system. Using immunohistochemical, electron microscopic, and molecular analyses, we provide evidence for the release of distinct extracellular vesicles from endfeet and microvilli of retinal Muller cells in adult mice in vivo. We identify VAMP5 as a Muller cell-specific SNARE component that is part of extracellular vesicles and responsive to ischemia, and we reveal differences between the secretomes of immunoaffinity-purified Muller cells and neurons in vitro. Our findings suggest extracellular vesicle-based communication as an important mediator of cellular interactions in the retina.

Automated summary

This study reveals the communication mechanism of Muller cells in the retina of adult mice through the release of extracellular vesicles. The Muller cell-specific SNARE protein VAMP5 is identified as a component of extracellular vesicles and is responsive to ischemia. Furthermore, differences in the secretomes between Muller cells and neurons in vitro are uncovered.