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 journalArticle

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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Azithromycin
Retinal Ganglion Cells
Reperfusion Injury
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Intraocular Pressure
Ischemia
Calpain
Eye Diseases
Extracellular Signal-Regulated MAP Kinases
Macrolides
Wounds and Injuries
Neuroprotective Agents
Gelatin
Retina
Cell Death
Anti-Inflammatory Agents
Up-Regulation
Western Blotting
Phosphorylation

Cite this

Varano, GP., Parisi, V., Adornetto, A., Cavaliere, F., Amantea, D., Nucci, C., ... Russo, R. (2017). Post-ischemic treatment with azithromycin protects ganglion cells against retinal ischemia/reperfusion injury in the rat. Molecular Vision, 23, 911-921.

Post-ischemic treatment with azithromycin protects ganglion cells against retinal ischemia/reperfusion injury in the rat. / Varano, GP; Parisi, Vincenzo; Adornetto, A; Cavaliere, F; Amantea, D; Nucci, C; Corasaniti, MT; Morrone, LA; Baggetta, G; Russo, R.

In: Molecular Vision, Vol. 23, 11.12.2017, p. 911-921.

Research output: Contribution to journalArticle

Varano, GP, Parisi, V, Adornetto, A, Cavaliere, F, Amantea, D, Nucci, C, Corasaniti, MT, Morrone, LA, Baggetta, G & Russo, R 2017, 'Post-ischemic treatment with azithromycin protects ganglion cells against retinal ischemia/reperfusion injury in the rat.', Molecular Vision, vol. 23, pp. 911-921.
Varano, GP ; Parisi, Vincenzo ; Adornetto, A ; Cavaliere, F ; Amantea, D ; Nucci, C ; Corasaniti, MT ; Morrone, LA ; Baggetta, G ; Russo, R. / Post-ischemic treatment with azithromycin protects ganglion cells against retinal ischemia/reperfusion injury in the rat. In: Molecular Vision. 2017 ; Vol. 23. pp. 911-921.
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T1 - Post-ischemic treatment with azithromycin protects ganglion cells against retinal ischemia/reperfusion injury in the rat.

AU - Varano, GP

AU - Parisi, Vincenzo

AU - Adornetto, A

AU - Cavaliere, F

AU - Amantea, D

AU - Nucci, C

AU - Corasaniti, MT

AU - Morrone, LA

AU - Baggetta, G

AU - Russo, R

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N2 - 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

AB - 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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