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Brimonidine is Neuroprotective in Animal Paradigm of Retinal Ganglion Cell Damage

To investigate the neuroprotective effect of brimonidine after retinal ischemia damage on mouse eye. Glaucoma is an optic neuropathy characterized by retinal ganglion cells (RGCs) death, irreversible peripheral and central visual field loss, and high intraocular pressure. Ischemia reperfusion (I/R)...

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Autores principales: Conti, Federica, Romano, Giovanni Luca, Eandi, Chiara Maria, Toro, Mario Damiano, Rejdak, Robert, Di Benedetto, Giulia, Lazzara, Francesca, Bernardini, Renato, Drago, Filippo, Cantarella, Giuseppina, Bucolo, Claudio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8333612/
https://www.ncbi.nlm.nih.gov/pubmed/34366858
http://dx.doi.org/10.3389/fphar.2021.705405
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author Conti, Federica
Romano, Giovanni Luca
Eandi, Chiara Maria
Toro, Mario Damiano
Rejdak, Robert
Di Benedetto, Giulia
Lazzara, Francesca
Bernardini, Renato
Drago, Filippo
Cantarella, Giuseppina
Bucolo, Claudio
author_facet Conti, Federica
Romano, Giovanni Luca
Eandi, Chiara Maria
Toro, Mario Damiano
Rejdak, Robert
Di Benedetto, Giulia
Lazzara, Francesca
Bernardini, Renato
Drago, Filippo
Cantarella, Giuseppina
Bucolo, Claudio
author_sort Conti, Federica
collection PubMed
description To investigate the neuroprotective effect of brimonidine after retinal ischemia damage on mouse eye. Glaucoma is an optic neuropathy characterized by retinal ganglion cells (RGCs) death, irreversible peripheral and central visual field loss, and high intraocular pressure. Ischemia reperfusion (I/R) injury model was used in C57BL/6J mice to mimic conditions of glaucomatous neurodegeneration. Mouse eyes were treated topically with brimonidine and pattern electroretinogram were used to assess the retinal ganglion cells (RGCs) function. A wide range of inflammatory markers, as well as anti-inflammatory and neurotrophic molecules, were investigated to figure out the potential protective effects of brimonidine in mouse retina. In particular, brain-derived neurotrophic factor (BDNF), IL-6, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its death receptor DR-5, TNF-α, GFAP, Iba-1, NOS, IL-1β and IL-10 were assessed in mouse retina that underwent to I/R insult with or without brimonidine treatment. Brimonidine provided remarkable RGCs protection in our paradigm. PERG amplitude values were significantly (p < 0.05) higher in brimonidine-treated eyes in comparison to I/R retinas. Retinal BDNF mRNA levels in the I/R group dropped significantly (p < 0.05) compared to the control group (normal mice); brimonidine treatment counteracted the downregulation of retinal BDNF mRNA in I/R eyes. Retinal inflammatory markers increased significantly (p < 0.05) in the I/R group and brimonidine treatment was able to revert that. The anti-inflammatory IL-10 decreased significantly (p < 0.05) after retinal I/R insult and increased significantly (p < 0.05) in the group treated with brimonidine. In conclusion, brimonidine was effective in preventing loss of function of RGCs and in regulating inflammatory biomarkers elicited by retinal I/R injury.
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spelling pubmed-83336122021-08-05 Brimonidine is Neuroprotective in Animal Paradigm of Retinal Ganglion Cell Damage Conti, Federica Romano, Giovanni Luca Eandi, Chiara Maria Toro, Mario Damiano Rejdak, Robert Di Benedetto, Giulia Lazzara, Francesca Bernardini, Renato Drago, Filippo Cantarella, Giuseppina Bucolo, Claudio Front Pharmacol Pharmacology To investigate the neuroprotective effect of brimonidine after retinal ischemia damage on mouse eye. Glaucoma is an optic neuropathy characterized by retinal ganglion cells (RGCs) death, irreversible peripheral and central visual field loss, and high intraocular pressure. Ischemia reperfusion (I/R) injury model was used in C57BL/6J mice to mimic conditions of glaucomatous neurodegeneration. Mouse eyes were treated topically with brimonidine and pattern electroretinogram were used to assess the retinal ganglion cells (RGCs) function. A wide range of inflammatory markers, as well as anti-inflammatory and neurotrophic molecules, were investigated to figure out the potential protective effects of brimonidine in mouse retina. In particular, brain-derived neurotrophic factor (BDNF), IL-6, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its death receptor DR-5, TNF-α, GFAP, Iba-1, NOS, IL-1β and IL-10 were assessed in mouse retina that underwent to I/R insult with or without brimonidine treatment. Brimonidine provided remarkable RGCs protection in our paradigm. PERG amplitude values were significantly (p < 0.05) higher in brimonidine-treated eyes in comparison to I/R retinas. Retinal BDNF mRNA levels in the I/R group dropped significantly (p < 0.05) compared to the control group (normal mice); brimonidine treatment counteracted the downregulation of retinal BDNF mRNA in I/R eyes. Retinal inflammatory markers increased significantly (p < 0.05) in the I/R group and brimonidine treatment was able to revert that. The anti-inflammatory IL-10 decreased significantly (p < 0.05) after retinal I/R insult and increased significantly (p < 0.05) in the group treated with brimonidine. In conclusion, brimonidine was effective in preventing loss of function of RGCs and in regulating inflammatory biomarkers elicited by retinal I/R injury. Frontiers Media S.A. 2021-07-21 /pmc/articles/PMC8333612/ /pubmed/34366858 http://dx.doi.org/10.3389/fphar.2021.705405 Text en Copyright © 2021 Conti, Romano, Eandi, Toro, Rejdak, Di Benedetto, Lazzara, Bernardini, Drago, Cantarella and Bucolo. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Conti, Federica
Romano, Giovanni Luca
Eandi, Chiara Maria
Toro, Mario Damiano
Rejdak, Robert
Di Benedetto, Giulia
Lazzara, Francesca
Bernardini, Renato
Drago, Filippo
Cantarella, Giuseppina
Bucolo, Claudio
Brimonidine is Neuroprotective in Animal Paradigm of Retinal Ganglion Cell Damage
title Brimonidine is Neuroprotective in Animal Paradigm of Retinal Ganglion Cell Damage
title_full Brimonidine is Neuroprotective in Animal Paradigm of Retinal Ganglion Cell Damage
title_fullStr Brimonidine is Neuroprotective in Animal Paradigm of Retinal Ganglion Cell Damage
title_full_unstemmed Brimonidine is Neuroprotective in Animal Paradigm of Retinal Ganglion Cell Damage
title_short Brimonidine is Neuroprotective in Animal Paradigm of Retinal Ganglion Cell Damage
title_sort brimonidine is neuroprotective in animal paradigm of retinal ganglion cell damage
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8333612/
https://www.ncbi.nlm.nih.gov/pubmed/34366858
http://dx.doi.org/10.3389/fphar.2021.705405
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