Immune stimulation recruits a subset of pro-regenerative macrophages to the retina that promotes axonal regrowth of injured neurons

Lien Andries, Daliya Kancheva, Luca Masin, Isabelle Scheyltjens, Hannah Van Hove, Karen De Vlaminck, Steven Bergmans, Marie Claes, Lies De Groef, Lieve Moons, Kiavash Movahedi

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Abstract

The multifaceted nature of neuroinflammation is highlighted by its ability to both aggravate and promote neuronal health. While in mammals retinal ganglion cells (RGCs) are unable to regenerate following injury, acute inflammation can induce axonal regrowth. However, the nature of the cells, cellular states and signalling pathways that drive this inflammation-induced regeneration have remained elusive. Here, we investigated the functional significance of macrophages during RGC de- and regeneration, by characterizing the inflammatory cascade evoked by optic nerve crush (ONC) injury, with or without local inflammatory stimulation in the vitreous. By combining single-cell RNA sequencing and fate mapping approaches, we elucidated the response of retinal microglia and recruited monocyte-derived macrophages (MDMs) to RGC injury. Importantly, inflammatory stimulation recruited large numbers of MDMs to the retina, which exhibited long-term engraftment and promoted axonal regrowth. Ligand-receptor analysis highlighted a subset of recruited macrophages that exhibited expression of pro-regenerative secreted factors, which were able to promote axon regrowth via paracrine signalling. Our work reveals how inflammation may promote CNS regeneration by modulating innate immune responses, providing a rationale for macrophage-centred strategies for driving neuronal repair following injury and disease.

Original languageEnglish
Article number85
Number of pages20
JournalActa Neuropathologica Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 24 May 2023

Keywords

  • Animals
  • Axons
  • Retina
  • Retinal Ganglion Cells
  • Macrophages
  • Inflammation
  • Optic Nerve Injuries
  • Mammals

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