Post-ischemic treatment with azithromycin protects ganglion cells against retinal ischemia/reperfusion injury in the rat.
Mol Vis
; 23: 911-921, 2017.
Article
em En
| MEDLINE
| ID: mdl-29296071
Purpose: Retinal ischemic phenomena occur in several ocular diseases that share the degeneration and death of retinal ganglion cells (RGCs) as the final event. We tested the neuroprotective effect of azithromycin, a widely used semisynthetic macrolide antibiotic endowed with anti-inflammatory and immunomodulatory properties, in a model of retinal ischemic injury induced by transient elevation of intraocular pressure in the rat. Methods: Retinal ischemia was induced in adult rats with transient elevation of intraocular pressure. RGCs were retrogradely labeled with Fluoro-Gold, and survival was assessed following a single dose of azithromycin given systemically at the end of the ischemia. The expression of death-associated proteins and extracellular signal-regulated kinase (ERK) activation was studied with western blotting. Expression and activity of matrix metalloproteinase-2 (MMP-2) and -9 were analyzed with gelatin zymography. Results: Acute post-injury administration of azithromycin significantly prevented RGC death. This effect was accompanied by reduced calpain activity and prevention of Bcl-2-associated death promoter (Bad) upregulation. The observed neuroprotection was associated with a significant inhibition of MMP-2/-9 gelatinolytic activity and ERK1/2 phosphorylation. Conclusions: Azithromycin provides neuroprotection by modifying the inflammatory state of the retina following ischemia/reperfusion injury suggesting potential for repurposing as a drug capable of limiting or preventing retinal neuronal damage.
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Base de dados:
MEDLINE
Assunto principal:
Doenças Retinianas
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Células Ganglionares da Retina
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Traumatismo por Reperfusão
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Azitromicina
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Modelos Animais de Doenças
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Antibacterianos
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article