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

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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

DOI 10.1523/jneurosci.4193-06.2007PMC PMC6672527

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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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Authors: Osakada, F., Ooto, S., Akagi, T., Mandai, M., Akaike, A., & Takahashi, M.
Affiliations: RIKEN (JP)
Kyoto University (JP)
ORCID: Osakada, Fumitaka
Ooto, Sotaro
Akagi, Tadamichi
Mandai, Michiko
Takahashi, Masayo
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2007-04-11
Volume: 27
Issue: 15
Pages: 4210-4219
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.4193-06.2007
PMC: PMC6672527
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: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 183 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Japan Society for the Promotion of Science
Topics: Health Sciences › Medicine › Ophthalmology › 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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Wnt Signaling Promotes Regeneration in the Retina of Adult Mammals

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