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Mol Vis. 2017 Dec 11;23:911-921. eCollection 2017.

Post-ischemic treatment with azithromycin protects ganglion cells against retinal ischemia/reperfusion injury in the rat.

Author information

1
Department of Pharmacy, Health and Nutritional Sciences, Section of Preclinical and Translational Pharmacology, Arcavacata di Rende, Italy.
2
Visual Neurophysiology and Neurophthalmology Research Unit, IRCCS G.B. Bietti Foundation, Roma.
3
Ophthalmology Unit, Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata" Rome, Italy.
4
Department of Health Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.

Abstract

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.

PMID:
29296071
PMCID:
PMC5741380
[Indexed for MEDLINE]
Free PMC Article

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