Effects of ocular injury and administration ofbrain-derived neurotrophic factor on survival and regrowth of axotomized retinalganglion cells.
Open accessAbstract
Optic nerve transection in adult rats results in the death of approximately 50% of the axotomized retinal ganglion cells (RGCs) by 1 week and nearly 90% by 2 weeks after injury. The capacity of brain-derived neurotrophic factor (BDNF) to prevent this early, severe loss of RGCs was investigated in vivo by intravitreal injections of BDNF [5 micrograms in 5 microliters of bovine serum albumin/phosphate-buffered saline (BSA/PBS)] or vehicle (5 microliters of BSA/PBS). Using quantitative anatomical techniques, we show that (i) all RGCs survived 1 week after a single injection of BDNF at the time of axotomy. (ii) RGC densities decreased in the BDNF-treated retinas by 2 weeks but remained significantly greater than in the untreated controls. (iii) An enhanced RGC survival was obtained with single injections of BDNF from 6 days before to 5 days after axotomy. (iv) Repeated injections resulted in greater numbers of surviving RGCs, an effect that declined to undetectable levels by 6 weeks. (v) There were indications for an endogenous local source of trophic support whose expression was triggered by ocular injury, particularly to the anterior part of the eye. (vi) With multiple BDNF injections, there was profuse axonal sprouting around the optic disc. This remarkable intraretinal growth was not, however, reflected in increased RGC innervation of the peripheral nerve grafts, which are known to facilitate regeneration when used as optic nerve substitutes.
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Co-administration of siAMPK and rapamycin blocked the effect of siAMPK on dendritic and synaptic rescue.
“Co-administration of siAMPK and rapamycin, an inhibitor of mTORC1 [30], blocked the effect of siAMPK on dendritic and synaptic rescue (Fig. 4I-Q)”
From AMPK hyperactivation promotes dendrite retraction, synaptic loss, and neuronal dysfunction in glaucoma (2021) · cites this paper as [30]
The citation is attached to the description of rapamycin as an mTORC1 inhibitor, while the rescue result is attributed to Fig. 4I–Q. The cited paper’s Materials and Methods and Results describe BDNF injections and retinal ganglion cell survival and regrowth; searches for rapamycin, mTORC1, siAMPK, and dendritic or synaptic rescue found no passage addressing the cited description or the rescue result. (LLM, conf=0.78)
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- Authors
- Mansour-Robaey, S., Clarke, D. B., Wang, Y. C., Bray, G. M., & Aguayo, A. J.
- Affiliations
- Montreal General Hospital (CA)
- ORCID
- Clarke, D B
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1994-03
- Volume
- 91
- Issue
- 5
- Pages
- 1632-1636
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC43217
- OpenAlex
- W1969811289
- Cited by
- 731
- References
- 29
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 8 · 2023: 9 · 2022: 6 · 2021: 15 · 2020: 15 · 2019: 17 · 2018: 28 · 2017: 10 · 2016: 27 · 2015: 25 · 2014: 33 · 2013: 21 · 2012: 22
- FWCI
- 9.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Keywords
- brain-derived neurotrophic factor, retinal ganglion cells, optic nerve axotomy, axon regeneration, axonal sprouting, neuroprotection, intravitreal injection, optic nerve transection, nerve grafts, retinal innervation
- MeSH terms
- Animals, Axons, Cell Survival, Eye Injuries, Female, Nerve Growth Factors, Nerve Regeneration, Nerve Tissue Proteins, Optic Nerve, Peripheral Nerves, Retinal Ganglion Cells, Rats, Sprague-Dawley, Brain-Derived Neurotrophic Factor, Optic Nerve Injuries, Rats
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