CNTF-mediated protection of photoreceptors requires initial activation of the cytokine receptor gp130 in Müller glial cells
Open accessAbstract
Significance: The cytokine CNTF has been approved by the FDA as a neuroprotective treatment for major retinal degenerative diseases. However, the mechanism of CNTF-triggered protection and CNTF-responsive cells in the retina remains unknown. Using molecular genetic analyses in a retinal degeneration mouse model, we identify the Müller glial cell as the direct initial target of exogenous CNTF signals. We provide evidence that CNTF signals stimulate a Müller glia and photoreceptor intercellular signaling loop involved in neuronal survival. Nonetheless, despite the marked improvement in photoreceptor morphology and survival, CNTF treatment does not result in a corresponding improvement of visual function. These results provide insight into the mechanism of CNTF action in the diseased retinas relevant to its clinical applications.
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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 Rhee et al., 2013
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- Authors
- Rhee, K. D., Nusinowitz, S., Chao, K., Yu, F., Bok, D., & Yang, X.-J.
- Affiliations
- Jules Stein Eye Institute, Department of Ophthalmology,
- University of California, Los Angeles (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-11-04
- Volume
- 110
- Issue
- 47
- Pages
- E4520-9
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3839707
- OpenAlex
- W2168681404
- Cited by
- 92
- References
- 60
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 4 · 2023: 6 · 2022: 10 · 2021: 4 · 2020: 10 · 2019: 4 · 2018: 10 · 2017: 3 · 2016: 10 · 2015: 10 · 2014: 7
- FWCI
- 4.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Eye Institute (R01EY019052, EY019052, EY-00331, P30EY000331)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Keywords
- ciliary neurotrophic factor, photoreceptor survival, Müller cells, gp130, retinitis pigmentosa, neuroprotection, STAT3 phosphorylation, ERK signaling, LiF, endothelin-2, retinal degeneration, lentiviral gene delivery, retinal transcriptome
- MeSH terms
- Analysis of Variance, Animals, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Immunohistochemistry, Mice, Transgenic, Retinal Degeneration, Blotting, Western, Signal Transduction, Lentivirus, Photoreceptor Cells, Vertebrate, Ciliary Neurotrophic Factor, Microscopy, Electron, Transmission, Cytokine Receptor gp130, Mice, Real-Time Polymerase Chain Reaction, Ependymoglial Cells
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