Effect of CNTF on retinal ganglion cell survival in experimental glaucoma
Open accessAbstract
PURPOSE: To assess the neuroprotective effect of virally mediated overexpression of ciliary-derived neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in experimental rat glaucoma. METHODS: Laser-induced glaucoma was produced in one eye of 224 Wistar rats after injection of adenoassociated viral vectors (type 2) containing either CNTF, BDNF, or both, with saline-injected eyes and noninjected glaucomatous eyes serving as the control. IOP was measured with a hand-held tonometer, and semiautomated optic nerve axon counts were performed by masked observers. IOP exposure over time was adjusted in multivariate regression analysis to calculate the effect of CNTF and BDNF. RESULTS: By multivariate regression, CNTF had a significant protective effect, with 15% less RGC axon death (P < 0.01). Both combined CNTF-BDNF and BDNF overexpression alone had no statistically significant improvement in RGC axon survival. By Western blot, there was a quantitative increase in CNTF and BDNF expression in retinas exposed to single viral vectors carrying each gene, but no increase with sequential injection of both vectors. CONCLUSIONS: These data confirm that CNTF can exert a protective effect in experimental glaucoma. The reason for the lack of observed effect in the BDNF overexpression groups is unclear, but it may be a function of the level of neurotrophin expression achieved.
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AAV delivery of BDNF and its receptor or CNTF promoted survival and function of retinal ganglion cells in models of optic nerve crush or retinal ganglion cell degeneration in a model for experimental glaucoma, respectively.
“Supporting the promise of this method, AAV delivery of BDNF and its receptor105 or CNTF106 promoted survival and function of retinal ganglion cells in models of optic nerve crush or retinal ganglion cell degeneration in a model for experimental glaucoma, respectively.”
From Gene Therapy for Retinal Degenerative Diseases: Progress, Challenges, and Future Directions (2023) · cites this paper as [106]
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- Authors
- Pease, M. E., Zack, D. J., Berlinicke, C., Bloom, K., Cone, F., Wang, Y., Klein, R. L., Hauswirth, W. W., & Quigley, H. A.
- Affiliations
- From the Departments of Ophthalmology,
- From the Departments of Ophthalmology,2Molecular Biology and Genetics, and3Neuroscience, the4Institute of Genetic Medicine, and
- Louisiana State University Health Sciences Center Shreveport (US)
- University of Florida (US)
- Johns Hopkins University (US)
- ORCID
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2009-05-01
- Volume
- 50
- Issue
- 5
- Pages
- 2194
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- PMC
- PMC2810634
- OpenAlex
- W2094688362
- Cited by
- 222
- References
- 88
- Citations by year
- 2026: 2 · 2025: 11 · 2024: 11 · 2023: 15 · 2022: 8 · 2021: 13 · 2020: 19 · 2019: 17 · 2018: 15 · 2017: 8 · 2016: 19 · 2015: 13 · 2014: 10 · 2013: 13 · 2012: 9
- FWCI
- 15.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Johns Hopkins University
- National Eye Institute (EY 13729, P30EY021721, R56EY002120, EY 08571, U10EY013729, #EY01765, EY 02120, P30EY008571, P30EY001765, R01EY011123, EY-11123, R01EY002120)
- Topics
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- ciliary neurotrophic factor, brain-derived neurotrophic factor, retinal ganglion cell survival, experimental glaucoma, laser-induced glaucoma, neuroprotection, adeno-associated virus vectors, gene overexpression, intraocular pressure, neurotrophins
- MeSH terms
- Dependovirus, Animals, Axons, Cell Count, Cell Survival, Disease Models, Animal, Gene Expression Regulation, Genetic Vectors, Glaucoma, Intraocular Pressure, Male, Optic Nerve Diseases, Plasmids, Retinal Ganglion Cells, Tonometry, Ocular, Blotting, Western, Genetic Therapy, Rats, Wistar, Brain-Derived Neurotrophic Factor, Cytoprotection, Ciliary Neurotrophic Factor, Rats
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