PUBLICATION

Injury-induced autophagy delays axonal regeneration after optic nerve damage in adult zebrafish

Authors
Beckers, A., Vanhunsel, S., Van Dyck, A., Bergmans, S., Masin, L., Moons, L.
ID
ZDB-PUB-210720-12
Date
2021
Source
Neuroscience   470: 52-69 (Journal)
Registered Authors
Keywords
Autophagy, Axonal regeneration, Central nervous system, Optic nerve crush, Zebrafish, mTOR
MeSH Terms
  • Optic Nerve
  • Animals
  • Optic Nerve Injuries*
  • Nerve Regeneration
  • Autophagy
  • Axons
  • Zebrafish
  • Nerve Crush
(all 8)
PubMed
34280491 Full text @ Neuroscience
Abstract
Optic neuropathies comprise a group of disorders in which the axons of retinal ganglion cells (RGCs), the retinal projection neurons conveying visual information to the brain, are damaged. This results in visual impairment or even blindness, which is irreversible as adult mammals lack the capacity to repair or replace injured or lost neurons. Despite intensive research, no efficient treatment to induce axonal regeneration in the central nervous system (CNS) is available yet. Autophagy, the cellular recycling response, was shown repeatedly to be elevated in animal models of optic nerve injury, and both beneficial and detrimental effects have been reported. In this study, we subjected spontaneously regenerating adult zebrafish to optic nerve damage (ONC) and revealed that autophagy is enhanced after optic nerve damage in zebrafish, both in RGC axons and somas, as well as in macroglial cells of the retina, the optic nerve and the visual target areas in the brain. Interestingly, the pattern of the autophagic response in the axons followed the spatiotemporal window of axonal regrowth, which suggests that autophagy is ongoing at the growth cones. Pharmacological inhibition of the recycling pathway resulted in accelerated RGC target reinnervation, possibly linked to increased mechanistic target of rapamycin (mTOR) activity, known to stimulate axonal regrowth. Taken together, these intriguing findings underline that further research is warranted to decipher if modulation of autophagy could be an effective therapeutic method to induce CNS regeneration.
Genes / Markers
Figures
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
vu12TgTransgenic Insertion
    zf155TgTransgenic Insertion
      1 - 2 of 2
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      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      No data available
      Fish
      No data available
      Antibodies
      Name Type Antigen Genes Isotypes Host Organism
      Ab1-elavlmonoclonalIgG2bMouse
      Ab2-gap43monoclonal
        IgG1Mouse
        Ab2-gfappolyclonalRabbit
        Ab4-atg5polyclonalRabbit
        Ab5-lcp1polyclonalIgGRabbit
        Ab14-rps6kmonoclonal
          IgGRabbit
          Ab17-sox2polyclonal
            Rabbit
            1 - 7 of 7
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            Orthology
            No data available
            Engineered Foreign Genes
            Marker Marker Type Name
            EGFPEFGEGFP
            1 - 1 of 1
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            Mapping
            No data available