Cited by 55Glaucoma and retinal disordersNeurological Disorders and TreatmentsRetinal Development and Disorders

An Investigation of the Neuroprotective Effects of Tetracycline Derivatives in Experimental Models of Retinal Cell Death

Baptiste, Darryl C, Hartwick, Andrew T. E, Jollimore, Christine A. B, Baldridge, William H, Seigel, Gail M, Kelly, Melanie E. M·2004·Molecular Pharmacology

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.

Integrity signals

Registry

Crossref · 10.1124/mol.104.001081

Cites

50 of 50 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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].”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review