Cited by 323Retinal Development and DisordersNeurogenesis and neuroplasticity mechanismsRetinal Diseases and Treatments

Wnt signaling promotes regeneration in the retina of adult mammals

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Osakada, Fumitaka, Ooto, Sotaro, Akagi, Tadamichi, Mandai, Michiko, Akaike, Akinori, Takahashi, Masayo·2007·The Journal of Neuroscience

Abstract

Regeneration in the mammalian CNS is severely limited. Unlike in the chick, current models hold that retinal neurons are never regenerated. Previously we demonstrated that, in the adult mammalian retina, Müller glia dedifferentiate and produce retinal cells, including photoreceptors, after acute neurotoxic injury in vivo . However, the number of newly generated retinal neurons is very limited. Here we demonstrate that Wnt (wingless-type MMTV integration site family)/β-catenin signaling promotes proliferation of Müller glia-derived retinal progenitors and neural regeneration after damage or during degeneration. Wnt3a treatment increases proliferation of dedifferentiated Müller glia >20-fold in the photoreceptor-damaged retina. Supplementation with retinoic acid or valproic acid induces differentiation of these cells primarily into Crx (cone rod homeobox)-positive and rhodopsin-positive photoreceptors. Notably, injury induces nuclear accumulation of β-catenin, cyclin D1 upregulation, and Wnt/β-catenin reporter activity. Activation of Wnt signaling by glycogen synthase kinase-3β inhibitors promotes retinal regeneration, and, conversely, inhibition of the signaling attenuates regeneration. This Wnt3a-mediated regeneration of retinal cells also occurs in rd mice, a model of retinal degeneration. These results provide evidence that Wnt/β-catenin signaling contributes to CNS regeneration in the adult mammal.

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Crossref · 10.1523/jneurosci.4193-06.2007

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Authors
Osakada, F., Ooto, S., Akagi, T., Mandai, M., Akaike, A., & Takahashi, M.
Affiliations
  • RIKEN (JP)
  • Kyoto University (JP)
Venue
The Journal of Neuroscience
Published
2007-04-11
Volume
27
Issue
15
Pages
4210-4219
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W1967448020
Cited by
322
References
60
Citations by year
2026: 5 · 2025: 4 · 2024: 7 · 2023: 10 · 2022: 19 · 2021: 13 · 2020: 15 · 2019: 13 · 2018: 14 · 2017: 15 · 2016: 18 · 2015: 24 · 2014: 26 · 2013: 25 · 2012: 19
FWCI
10.59
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Japan Society for the Promotion of Science
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
Keywords
Wnt/β-catenin signaling, retinal regeneration, retinal progenitor cells, photoreceptor regeneration, Wnt3a, retinoic acid, valproic acid, CRX, rhodopsin, glycogen synthase kinase-3β, cyclin D1, retinal degeneration, central nervous system regeneration
MeSH terms
Animals, Macaca fascicularis, Male, Mice, Transgenic, Nerve Regeneration, Organ Culture Techniques, Retina, Signal Transduction, Wnt Proteins, Mice, Rats, Wnt3 Protein, Wnt3A Protein

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