Minocycline upregulates pro-survival genes and downregulates pro-apoptotic genes in experimental glaucoma.
Graefes Arch Clin Exp Ophthalmol
; 252(5): 761-72, 2014 May.
Article
em En
| MEDLINE
| ID: mdl-24566901
ABSTRACT
PURPOSE:
Minocycline, a second-generation tetracycline with anti-inflammatory and anti-apoptotic properties, was reported to be neuroprotective in experimental glaucoma and optic nerve transection as well as in other neurodegenerative diseases. The purpose of this study was to investigate the mechanism underlying that neuroprotective effect in murine glaucoma.METHODS:
Elevated intraocular pressure was induced in 159 rats by the translimbal photocoagulation laser model. Minocycline 22 mg/kg or saline was injected intraperitoneally starting 3 days before the induction of glaucoma, and continued daily until the animals were sacrificed. The effect of minocycline on gene expression was evaluated using a quantitative polymerase chain reaction (PCR) array for apoptosis. The involvement of selected pro-apoptotic, pro-survival, and inflammatory genes was further analyzed by quantitative real-time PCR at multiple time points. Immunohistochemistry was used to study the effect of minocycline on microglial activation and to localize Bcl-2 changes.RESULTS:
Minocycline significantly increased the anti-apoptotic gene Bcl-2 expression at day 8 and day 14 after the induction of glaucoma (p = 0.04 and p = 0.03 respectively), and decreased IL-18 expression in the retina at day 14 and day 30 (p = 0.04 and p < 0.001 respectively). PCR arrays suggested that additional genes were affected by minocycline, including Tp53bp2, TRAF4, osteoprotegerin, caspase 1 and 4, and members of the tumor necrosis factor superfamily. Additionally, minocycline decreased the amount of activated microglia in glaucomatous eyes.CONCLUSIONS:
These results suggest that minocycline upregulates pro-survival genes and downregulates apoptotic genes, thus shifting the balance toward the anti-apoptotic side in experimental glaucoma.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças do Nervo Óptico
/
Regulação da Expressão Gênica
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Glaucoma
/
Modelos Animais de Doenças
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Proteínas Reguladoras de Apoptose
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Minociclina
/
Antibacterianos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article