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

GP Varano, Vincenzo Parisi, A Adornetto, F Cavaliere, D Amantea, C Nucci, MT Corasaniti, LA Morrone, G Baggetta, R Russo

Research output: Contribution to journalArticlepeer-review

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
Original languageEnglish
Pages (from-to)911-921
Number of pages11
JournalMolecular Vision
Volume23
Publication statusPublished - Dec 11 2017

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