Inflammation is a critical factor for successful regeneration of the adult zebrafish retina in response to diffuse light lesion

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

Inflammation can lead to persistent and irreversible loss of retinal neurons and photoreceptors in mammalian vertebrates. In contrast, in the adult zebrafish brain, acute neural inflammation is both necessary and sufficient to stimulate regeneration of neurons. Here, we report on the critical, positive role of the immune system to support retina regeneration in adult zebrafish. After sterile ablation of photoreceptors by phototoxicity, we find rapid response of immune cells, especially monocytes/microglia and neutrophils, which returns to homeostatic levels within 14 days post lesion. Pharmacological or genetic impairment of the immune system results in a reduced Müller glia stem cell response, seen as decreased reactive proliferation, and a strikingly reduced number of regenerated cells from them, including photoreceptors. Conversely, injection of the immune stimulators flagellin, zymosan, or M-CSF into the vitreous of the eye, leads to a robust proliferation response and the upregulation of regeneration-associated marker genes in Müller glia. Our results suggest that neuroinflammation is a necessary and sufficient driver for retinal regeneration in the adult zebrafish retina.

Details

Original languageEnglish
Article number1332347
JournalFrontiers in cell and developmental biology
Volume12
Publication statusPublished - 2024
Peer-reviewedYes

External IDs

ORCID /0000-0003-0283-0211/work/165063159

Keywords

ASJC Scopus subject areas

Keywords

  • immune suppression, M-CSF, microglia, Müller glia, NF-κB pathway, regeneration, retina, zebrafish