Microglia support regeneration of rod photoreceptors in larval zebrafish retina through Nrf2-independent mechanisms

The molecular and cellular components of successful regeneration of complex tissues in zebrafish are a major area of investigation. Previous work by our lab indicates a redox function for retinal microglia in the first 48 hours following acute injury to rod photoreceptors in the larval zebrafish retina. In addition, recent literature suggests that microglia provide signals that impact the regenerative response in the damaged retina. Here, we investigate the requirement of microglia and the redox-responsive transcription factor Nrf2 in the spontaneous regeneration of rod photoreceptors in the larval zebrafish retina. We used irf8 mutants which are deficient in microglia, and mutant zebrafish lacking a functional copy of the gene nfe2l2a, which encodes a zebrafish ortholog of Nfe2l2/Nrf2. Our results indicate that microglia support the production of regenerated rods following their ablation. However, although detection of reactive oxygen species was increased in nfe2l2a mutant microglia following rod ablation, the regeneration of rods was not impacted in nfe2l2a mutants. Collectively, our results indicate a role for microglia in supporting the production of regenerated retinal neurons while also indicating that Nrf2-independent mechanisms can likely provide redox functions during rod regeneration.