PUBLICATION

Ablation of mpeg+ Macrophages Exacerbates mfrp-Related Hyperopia

Authors
Brandt, Z.J., Collery, R.F., Besharse, J.C., Link, B.A.
ID
ZDB-PUB-211217-14
Date
2021
Source
Investigative ophthalmology & visual science   62: 13 (Journal)
Registered Authors
Besharse, Joseph C., Collery, Ross, Link, Brian
Keywords
none
MeSH Terms
  • Animals, Genetically Modified
  • Immunohistochemistry
  • Membrane Proteins/genetics*
  • Membrane Proteins/physiology*
  • Phenotype
  • Zebrafish
  • Macrophages/physiology*
  • Apoptosis
  • Emmetropia/physiology
  • Tomography, Optical Coherence
  • Animals
  • Refraction, Ocular
  • Cell Proliferation
  • Microscopy, Electron, Transmission
  • Eye Proteins/genetics*
  • Anti-Infective Agents/pharmacology
  • Sclera/metabolism
  • Sclera/ultrastructure
  • Zebrafish Proteins/physiology*
  • Collagen/metabolism
  • Collagen/ultrastructure
  • Hyperopia/diagnostic imaging
  • Hyperopia/genetics
  • Hyperopia/physiopathology*
  • Metronidazole/pharmacology
  • Microscopy, Fluorescence
(all 26)
PubMed
34913948 Full text @ Invest. Ophthalmol. Vis. Sci.
Abstract
Purpose Proper refractive development of the eye, termed emmetropization, is critical for focused vision and is impacted by both genetic determinants and several visual environment factors. Improper emmetropization caused by genetic variants can lead to congenital hyperopia, which is characterized by small eyes and relatively short ocular axial length. To date, variants in only four genes have been firmly associated with human hyperopia, one of which is MFRP. Zebrafish mfrp mutants also have hyperopia and, similar to reports in mice, exhibit increased macrophage recruitment to the retina. The goal of this research was to examine the effects of macrophage ablation on emmetropization and mfrp-related hyperopia.
Methods We utilized a chemically inducible, cell-specific ablation system to deplete macrophages in both wild-type and mfrp mutant zebrafish. Spectral-domain optical coherence tomography was then used to measure components of the eye and determine relative refractive state. Histology, immunohistochemistry, and transmission electron microscopy were used to further study the eyes.
Results Although macrophage ablation does not cause significant changes to the relative refractive state of wild-type zebrafish, macrophage ablation in mfrp mutants significantly exacerbates their hyperopic phenotype, resulting in a relative refractive error 1.3 times higher than that of non-ablated mfrp siblings.
Conclusions Genetic inactivation of mfrp leads to hyperopia, as well as abnormal accumulation of macrophages in the retina. Ablation of the mpeg1-positive macrophage population exacerbates the hyperopia, suggesting that macrophages may be recruited in an effort help preserve emmetropization and ameliorate hyperopia.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
No data available
Phenotype
Fish Conditions Stage Phenotype Figure
WTchemical treatment by environment: metronidazoleDays 45-89
WTchemical treatment by environment: metronidazoleDays 45-89
WTchemical treatment by environment: metronidazoleDays 45-89
mfrpmw78/+; w202Tg/w202Tgstandard conditionsDays 45-89
mfrpmw78/+; w202Tg/w202Tgstandard conditionsDays 45-89
mfrpmw78/+; w202Tg/w202Tgstandard conditionsDays 45-89
mfrpmw78/+; w202Tg/w202Tgstandard conditionsDays 45-89
mfrpmw78/+; w202Tg/w202Tgstandard conditionsDays 45-89
mfrpmw78/+; w202Tg/w202Tgstandard conditionsDays 45-89
mfrpmw78/+; w202Tg/w202Tgstandard conditionsDays 45-89
1 - 10 of 75
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
mw78
    		Small Deletion
    w202TgTransgenic Insertion
      1 - 2 of 2
      Show
      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      No data available
      Fish
      Fish
      mfrpmw78/mw78
      mfrpmw78/mw78; w202Tg/w202Tg
      mfrpmw78/+; w202Tg/w202Tg
      w202Tg/w202Tg
      WT
      1 - 5 of 5
      Show
      Antibodies
      Name Type Antigen Genes Isotypes Host Organism
      Ab-4C4monoclonal
        		IgG1Mouse
        Ab5-lcp1polyclonalIgGRabbit
        AB9-GFPmonoclonalIgG2aMouse
        1 - 3 of 3
        Show
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        EYFPEFGEYFP
        NTREFGNTR
        1 - 2 of 2
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        Mapping
        No data available
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        Citation
        Brandt, Z.J., Collery, R.F., Besharse, J.C., Link, B.A. (2021) Ablation of mpeg+ Macrophages Exacerbates mfrp-Related Hyperopia. Investigative ophthalmology & visual science. 62:13.