PUBLICATION

The immune response is a critical regulator of zebrafish retinal pigment epithelium regeneration

Authors
Leach, L.L., Hanovice, N.J., George, S.M., Gabriel, A.E., Gross, J.M.
ID
ZDB-PUB-210520-4
Date
2021
Source
Proceedings of the National Academy of Sciences of the United States of America   118(21): (Journal)
Registered Authors
Gross, Jeffrey, Hanovice, Nick, Leach, Lyndsay
Keywords
inflammation, macrophage, microglia, regeneration, retinal pigment epithelium
Datasets
GEO:GSE155295, GEO:GSE155294
MeSH Terms
  • Animals
  • Animals, Genetically Modified/genetics
  • Animals, Genetically Modified/growth & development
  • Blindness/genetics*
  • Blindness/parasitology
  • Blindness/therapy
  • Disease Models, Animal
  • Gene Expression Regulation, Developmental/genetics
  • Humans
  • Immunity/genetics*
  • Interleukins/genetics*
  • Microglia/metabolism
  • Microglia/pathology
  • Mutation/genetics
  • Regeneration/genetics*
  • Retinal Pigment Epithelium/growth & development
  • Retinal Pigment Epithelium/pathology
  • Transcriptome/genetics
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish Proteins/genetics*
PubMed
34006636 Full text @ Proc. Natl. Acad. Sci. USA
Abstract
Loss of the retinal pigment epithelium (RPE) because of dysfunction or disease can lead to blindness in humans. Harnessing the intrinsic ability of the RPE to self-repair is an attractive therapeutic strategy; however, mammalian RPE is limited in its regenerative capacity. Zebrafish possess tremendous intrinsic regenerative potential in ocular tissues, including the RPE, but little is known about the mechanisms driving RPE regeneration. Here, utilizing transgenic and mutant zebrafish lines, pharmacological manipulations, transcriptomics, and imaging analyses, we identified elements of the immune response as critical mediators of intrinsic RPE regeneration. After genetic ablation, the RPE express immune-related genes, including leukocyte recruitment factors such as interleukin 34 We demonstrate that macrophage/microglia cells are responsive to RPE damage and that their function is required for the timely progression of the regenerative response. These data identify the molecular and cellular underpinnings of RPE regeneration and hold significant potential for translational approaches aimed toward promoting a pro-regenerative environment in mammalian RPE.
Errata / Notes
Correction: https://www.pnas.org/doi/10.1073/pnas.2017198118
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping