Wnt signaling promotes regeneration in the retina of adult mammals
Open accessAbstract
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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Mammalian Müller glia have only limited regenerative capacity under special conditions.
“they only exhibit a limited regenerative potential under special conditions”
From HB-EGF is Necessary and Sufficient for Müller Glia Dedifferentiation and Retina Regeneration (2012) · cites this paper as Osakada et al., 2007
In mammals, β-catenin is associated with a very limited amount of Müller glia proliferation, while pStat3 is associated with injury-induced gliosis.
“It is interesting that in mammals, β-catenin has been associated with a very limited amount of MG proliferation while pStat3 has been associated with injury-induced gliosis (Osakada et al., 2007; Peterson et al., 2000; Rhee et al., 2013; Xue et al., 2011).”
From Retinal injury, growth factors, and cytokines converge on β-catenin and pStat3 signaling to stimulate retina regeneration (2014) · cites this paper as Osakada et al., 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
- Publisher
- Society for Neuroscience
- Published
- 2007-04-11
- Volume
- 27
- Issue
- 15
- Pages
- 4210-4219
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- 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
- 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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