Cited by 92Retinal Development and DisordersRetinal Diseases and TreatmentsGlaucoma and retinal disorders

CNTF-mediated protection of photoreceptors requires initial activation of the cytokine receptor gp130 in Müller glial cells

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Rhee, Kun Do, Nusinowitz, Steven, Chao, Kevin, Yu, Fei, Bok, Dean, Yang, Xian-Jie·2013·Proceedings of the National Academy of Sciences

Abstract

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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Crossref · 10.1073/pnas.1303604110

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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
Published
2013-11-04
Volume
110
Issue
47
Pages
E4520-9
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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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