June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
The Role of Microglia in Müller Glia-Dependent Regeneration of the Light-Damaged Adult Zebrafish Retina
Author Affiliations & Notes
  • Celine Lu
    University of Notre Dame Department of Biological Sciences, Notre Dame, Indiana, United States
  • David R Hyde
    University of Notre Dame Department of Biological Sciences, Notre Dame, Indiana, United States
  • Footnotes
    Commercial Relationships   Celine Lu None; David Hyde None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1591. doi:
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      Celine Lu, David R Hyde; The Role of Microglia in Müller Glia-Dependent Regeneration of the Light-Damaged Adult Zebrafish Retina. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1591.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Zebrafish possess the ability to regenerate neurons and restore vision following a variety of retinal insults. This regeneration response requires two retinal glial cell types, microglia and Müller glia (MG). Retinal damage induces MG to reprogram and divide asymmetrically to produce a neuronal progenitor, which proliferates and differentiates into retinal neurons. However, it is unclear how these two cell types interact with each other during regeneration. This study focuses on microglia activities in response to retinal damage to further understand how they might regulate the MG response in the adult zebrafish retina.

Methods : We used a light damage model to induce photoreceptor cell death. Drug treatment and morpholino-mediated gene knockdown were utilized to inhibit microglia and inflammatory cytokines. Immunohistochemistry using LCP-1, PCNA, and TUNEL was used to visualized microglia and MG behaviors. qRT-PCR was used to examine expression of target cytokines during light damage.

Results : Upon light damage, microglia were activated, migrated to the damaged retinal layer, and phagocytosed dying photoreceptors, demonstrating that microglia responded to photoreceptor cell death. To examine the importance of microglia during retinal damage, Dexamethasone and Pexidartinib were used to ablate microglia. Damaged retinas treated with both drugs revealed a significant reduction in the number of microglia and proliferating MG following light-induced photoreceptor cell death. Thus, microglia are required for MG proliferation during light damage. We examined the expression of various inflammatory cytokines in microglia by qRT-PCR and single-cell RNA-Seq. We found a rapid increase in the expression of several pro-inflammatory cytokines shortly after damage started, followed by an increase in anti-inflammatory cytokines. We reduced the expression of both pro- and anti-inflammatory cytokines (Il-1b and Il-10, respectively) using morpholinos and inhibitors and determined the effect on regeneration.

Conclusions : We demonstrate that microglia interact and communicate with MG during light damage. Interestingly, our data demonstrates that ablating microglia or inhibiting expression of certain inflammatory cytokines diminishes MG proliferation. Altogether, these findings provide new insights to the importance of microglia signaling to MG in the regenerating retina.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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