June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Photoreceptor regeneration occurs normally following light damage in microglia-deficient zebrafish irf8 mutants
Author Affiliations & Notes
  • Brian D Perkins
    Ophthalmic Research, Cleveland Clinic, Cleveland, Ohio, United States
  • Ping Song
    Ophthalmic Research, Cleveland Clinic, Cleveland, Ohio, United States
  • Lana Pollock
    Ophthalmic Research, Cleveland Clinic, Cleveland, Ohio, United States
  • Rupesh Singh
    Ophthalmic Research, Cleveland Clinic, Cleveland, Ohio, United States
  • Bela Anand-Apte
    Ophthalmic Research, Cleveland Clinic, Cleveland, Ohio, United States
  • Footnotes
    Commercial Relationships   Brian Perkins None; Ping Song None; Lana Pollock None; Rupesh Singh None; Bela Anand-Apte None
  • Footnotes
    Support  NIH Grants R01EY017037, R01EY030574, P30EY025585, and Research to Prevent Blindness (RPB) Challenge Grant, Cleveland Eye Bank Foundation Grant
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1622. doi:
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    • Get Citation

      Brian D Perkins, Ping Song, Lana Pollock, Rupesh Singh, Bela Anand-Apte; Photoreceptor regeneration occurs normally following light damage in microglia-deficient zebrafish irf8 mutants. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1622.

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

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Abstract

Purpose : Both acute injury and chronic degeneration triggers an inflammatory response in the zebrafish retina that is critical for stimulating regeneration of photoreceptors. Previous studies found that pharmacological-depletion of microglia inhibited Müller glia driven regeneration in zebrafish. The purpose here was to determine if photoreceptor regeneration occurred in zebrafish irf8 mutants that are chronically depleted of microglia.

Methods : The microglia-deficient irf8 mutant and the cep290 mutant lines were used for this study. The Tg(l-fabp:DBP-GFP) transgenic line was used to visualize the blood-retinal-barrier (BRB) in vivo using Confocal scanning laser ophthalmoscopy (cSLO). Immunohistochemistry was performed on retinal cryosections to monitor retinal cell types. Acute injury was generated by exposing animals to high intensity light. A minimum of 6 animals per group were tested. Data was quantified and analyzed using ANOVA with post hoc comparisons.

Results : Retinal architecture developed normally in zebrafish irf8 mutants. Cone numbers declined by 15% by 10 months post fertilization (mpf) in irf8 mutants. Following light damage, Müller glia entered the cell cycle and proliferated similar to wild-type siblings. At 1 month of recovery following acute light damage, the density of regenerated photoreceptors in irf8 mutants at 6 mpf was not different from wild-type animals. No observable damage to the BRB was found following acute light damage, suggesting that circulating microglia/macrophages did not enter the retina from the vasculature. Compared to the cep290 model of chronic retinal degeneration, irf8;cep290 double mutants exhibited reduced inflammation and cone degeneration was rescued. At 1 month of recovery following acute light damage to 6 mpf irf8;cep290 double mutants, however, a significant decrease in regenerated photoreceptors was observed.

Conclusions : In contrast to prior results, Müller glia proliferation and cone regeneration following acute damage occur normally in irf8 mutants, suggesting that inflammatory signaling from other retinal cells initiates regeneration. Finally, we show that regeneration is severely compromised in cep290;irf8 mutants, suggesting that microglia may contribute other roles. Our results indicate that the chronic absence of microglia is compatible with regeneration in zebrafish.

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

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