Brain-derived neurotrophic factor reduces TrkB protein and mRNA in the normal retina and following optic nerve crush in adult rats
Abstract
Brain-derived neurotrophic factor (BDNF) is a well-known retinal neuroprotectant, but its effectiveness is limited: higher doses do not yield increased cell survival, multiple applications are not additive, and long-term delivery does not reverse, ganglion cell death. These limitations might reflect either injury- or BDNF-induced retinal changes in TrkB, the high affinity tyrosine kinase receptor used by BDNF. Retinal levels of TrkB protein and mRNA were measured in rats following intravitreal application of BDNF alone, optic nerve crush alone, and both. Full-length receptor protein levels (TrkB.FL) were determined by Western blot analysis and mRNA (trkB.FL) levels were measured using RNAse protection assay (RPA). BDNF alone produced a rapid and prolonged decrease in normal retina TrkB.FL. Nerve crush also resulted in decreased TrkB.FL, but the reduction was not apparent before 2-week post-crush. BDNF applied at the time of the crush yielded reductions in TrkB.FL similar to that of BDNF alone. With respect to TrkB mRNA levels, injection of BDNF into normal eyes and optic nerve crush alone showed bell-shaped patterns of change: approximately 50% below normal at 24-h post-procedure, approximately 50% above normal at 3 days, normal at 7 days, and approximately 50% below normal at 2-week post-procedure. When BDNF and nerve crush were combined, trkB-FL levels reached 90% of normal 1-week post-crush/injection. The data suggest that the limitation of BDNF in promoting ganglion cell survival following optic nerve injury results, in part, due to drug-induced down-regulation of the full-length TrkB receptor needed to activate intracellular pathways.
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Recombinant human BDNF cross-reacts with cells of rat origin.
“recombinant human BDNF (rhBDNF; R&D Systems, Minneapolis, MN, USA), which is known to cross-react with cells of rat origin [28].”
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Neurotrophic Factors in Glaucoma and Innovative Delivery Systems
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“However, high-doses BDNF as exposed on cultured rat hippocampal neurons and intravitreally injected in animal models of optic nerve injury, caused a rapid and significant downregulation of TrkB expression which reduced BDNF effectiveness [68,69].”
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“…nature of neurotrophic factors and their effects on RGCs are likely varied, research has demonstrated that RGCs tend to become acclimated to elevated levels of these neurotrophic factors and become desensitized to their effects, often through the downregulation of specific receptors[38-40].”
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Signaling Through the Neurotrophin Receptors
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Autocrine and paracrine interactions and neuroprotection in glaucoma
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“Because this treatment strategy provides neurons with a slower and more constant source of trophic material, it is less likely to overwhelm the available receptors and result in their downregulation (Sommerfeld et al. 2000; Chen and Weber 2004; Frank et al. 1996).”
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“To the best of our knowledge, only a few studies have investigated the effects of BDNF on intact rodent eyes (e.g., the effect on the TrkB receptor and GFAP expressions) [23,24].”
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Optic Neuropathy and Ganglion Cell Degeneration in Glaucoma
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WITHDRAWN: Reprint of: Mechanisms of retinal ganglion cell injury and defense in glaucoma
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Neurotrophins - Players in the regulation of neuronal survival and apoptosis
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Muller glia-derived exosomes and their microRNA cargo–potential for glaucoma therapies
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Adult Stem Cell Treatment for Central Nervous System Injury
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“Bolus NTF administration that delivers a transient high peak of NTF down-regulates TrK receptors [25, 26], suggesting that delivery of a sustained lower dose may be a more effective treatment regime.”
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Stem Cell Strategies for Optic Nerve Protection
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Optic nerve regeneration in adult rat
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Brain-derived neurotrophic factor in age-related macular degeneration
Liao, H. (2026) · European Journal of Ophthalmology · doi:10.1177/11206721261427214
“118 Thus, establishing the expression pro fi le of BDNF and TrkB receptor in human AMD is essential to determine the optimal timing and dose of BDNF treatment.”
- Authors
- Chen, H., & Weber, A. J.
- Affiliations
- University of Tennessee Health Science Center (US)
- Michigan State University (US)
- Corresponding author
- Weber, Arthur J
- ORCID
- Weber, Arthur J
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2004-06
- Volume
- 1011
- Issue
- 1
- Pages
- 99-106
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W1986504481
- Cited by
- 75
- References
- 40
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2022: 5 · 2021: 1 · 2020: 4 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 6 · 2014: 5 · 2013: 5 · 2012: 4
- FWCI
- 1.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Michigan State University
- National Institutes of Health
- National Eye Institute (EY11159, R01EY011159)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- brain-derived neurotrophic factor, TrkB receptor, optic nerve crush, retinal ganglion cell survival, neuroprotection, receptor down-regulation, optic nerve injury
- MeSH terms
- Animals, Humans, Nerve Crush, Retina, Time Factors, Blotting, Western, Brain-Derived Neurotrophic Factor, Optic Nerve Injuries, Receptor, trkB, Electrophoretic Mobility Shift Assay, Rats
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