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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.
Sec. Molecular and Cellular Pathology
Volume 12 - 2024 | doi: 10.3389/fcell.2024.1495586

Forced MyD88 signaling in microglia impacts the production and survival of regenerated retinal neurons

Provisionally accepted
Jordan E Rumford Jordan E Rumford 1Ailis Grieshaber Ailis Grieshaber 1Samantha Lewiston Samantha Lewiston 1Jordan L Reed Jordan L Reed 1,2Samuel S Long Samuel S Long 3Diana Marie Mitchell Diana Marie Mitchell 1*
  • 1 University of Idaho, Moscow, United States
  • 2 North Idaho College, Coeur d'Alene, Idaho, United States
  • 3 Lewis Clark State College, Lewiston, ID, United States

The final, formatted version of the article will be published soon.

    Inflammation and microglia appear to be key factors influencing the outcome of retinal regeneration following acute retinal damage. Despite such findings, direct connection of microglia-specific inflammatory factors as drivers of regenerative responses in the retina are still not defined, and intracellular pathways activated to stimulate such signals from microglia are currently unknown. We became interested in MyD88 regulation in microglia because transcriptomic datasets suggest myd88 could be regulated temporally in zebrafish microglia responding to damage in the central nervous system. MyD88 is an intracellular molecular adaptor that initiates signaling cascades downstream of several innate immune receptors, and probably most well-known for inducing gene expression of pro-inflammatory factors. Using zebrafish, which spontaneously regenerate retinal neurons after acute retinal damage, we studied the effects of overactivation of MyD88 signaling in microglia and macrophages on the Müller glia-mediated regenerative response. Our results indicate that increased MyD88 signaling in microglia/macrophages impacts the initial response of Müller glia entering a regenerative response after acute, neurotoxin-induced retinal damage to inner retinal neurons. In addition, increased MyD88 signaling in microglia/macrophages resulted in reduced survival of inner retinal neurons in regenerated retinas. This work supports the idea that temporal control of inflammatory signaling is a key component in the production of MG-derived progenitors yet further indicates that such control is important for differentiation and survival of regenerated neurons.

    Keywords: Microglia, Retina, Regeneration, Inflammation, MyD88, NFkB, Müller glia, Zebrafish

    Received: 12 Sep 2024; Accepted: 07 Nov 2024.

    Copyright: © 2024 Rumford, Grieshaber, Lewiston, Reed, Long and Mitchell. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Diana Marie Mitchell, University of Idaho, Moscow, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.