An Investigation of the Neuroprotective Effects of Tetracycline Derivatives in Experimental Models of Retinal Cell Death
Abstract
The purpose of this study was to determine the efficacy and putative mechanisms of action of tetracycline and minocycline in inhibiting retinal cell apoptosis after glutamate-induced excitotoxicity and trophic factor deprivation in a retinal cell line (E1A-NR.3) and in primary mixed retinal cell cultures. In addition, a differentiated PC-12 cell line was used to determine whether minocycline was neuroprotective after trophic withdrawal in a pure neuronal cell line devoid of glia. Results from this study demonstrated that minocycline, but not tetracycline, is protective in in vitro models of excitotoxicity-induced retinal cell apoptosis. Moreover, the protective effects provided by minocycline in retinal cells seemed independent of actions on N-methyl-D-aspartate receptors (NMDARs) and glutamate receptor-mediated Ca(2+) influx. Doses of the NMDAR antagonist MK-801 (dizocilpine) and minocycline that alone provided no significant neuroprotection resulted in enhanced retinal cell survival when applied concurrently, suggestive of distinct signaling pathways, and minocycline was without effect on glutamate-induced Ca(2+) influx, as assessed by calcium imaging. Minocycline was also neuroprotective after trophic factor withdrawal, producing a decrease in apoptosis and caspase-3 activation in both retinal cells and the PC-12 neuronal-like cell line. These results support a role for minocycline as a retinal neuroprotectant and demonstrate that the antiapoptotic actions of minocycline in retinal cells do not arise from the blockage of NMDARs or glutamate receptor-mediated Ca(2+) influx but do involve inhibition of caspase-3 activation. In addition, the survival-promoting actions of minocycline may arise via actions on both neuronal and non-neuronal cell targets.
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Minocycline modulates glutamate transmission by reducing glutamate release and excitotoxicity, and may indirectly target the monoaminergic system.
“modulates glutamate transmission reducing glutamate release and excitotoxicity, and may indirectly target the monoaminergic system [101].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [101]
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Huang, P.-Y., & Lin, C. (2014) · Taiwan Veterinary Journal · doi:10.1142/s1682648514500115 · Cited by 1 · see citing works
A regeneration strategy for spinal cord injury
Nordblom, J. (2012) · Figshare
Sato, F., Braga, S. F., Santos, H. F. D., & Galvao, D. S. (2007) · arXiv (Cornell University) · doi:10.48550/arxiv.0708.2931
Huang, P.-Y., & Lin, C. (2013) · 臺灣獸醫學雜誌
Minocycline in Cerebral Ischemia and Excitotoxicity
Koıstınaho, J., & Koistinaho, M. (2006) · Springer eBooks · doi:10.1007/978-0-387-30383-3_14
Interaction Between RGC Bodies and Glia
Kashiwagi, K. (2014) · Springer eBooks · doi:10.1007/978-4-431-54965-9_11
- Authors
- Baptiste, D. C., Hartwick, A. T. E., Jollimore, C. A. B., Baldridge, W. H., Seigel, G. M., & Kelly, M. E. M.
- Affiliations
- Dalhousie University (CA)
- Venue
- Molecular Pharmacology
- Publisher
- Elsevier BV
- Published
- 2004-11
- Volume
- 66
- Issue
- 5
- Pages
- 1113-1122
- ISSN
- 0026-895X (ISSN-L)
- OpenAlex
- W2060952492
- Cited by
- 55
- References
- 50
- Citations by year
- 2020: 3 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 4 · 2014: 6 · 2013: 5 · 2012: 3
- FWCI
- 7.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- minocycline, tetracycline, retinal neuroprotection, retinal cell apoptosis, glutamate excitotoxicity, trophic factor deprivation, caspase-3 activation, NMDA receptor antagonism, MK-801, calcium influx, PC12 cells, glaucoma
- MeSH terms
- Animals, Cells, Cultured, Drug Interactions, Enzyme Activation, Minocycline, Retina, Tetracyclines, Culture Media, Serum-Free, Cell Death, Neuroprotective Agents, Glutamic Acid, Caspases, Rats, Caspase 3
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