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Brimonidine prevents neurodegeneration in a mouse model of normal tension glaucoma

Glaucoma is one of the leading causes of irreversible blindness that is characterized by progressive degeneration of optic nerves and retinal ganglion cells (RGCs). In the mammalian retina, excitatory amino-acid carrier 1 (EAAC1) is expressed in neural cells, including RGCs, and the loss of EAAC1 le...

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Autores principales: Semba, K, Namekata, K, Kimura, A, Harada, C, Mitamura, Y, Harada, T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123097/
https://www.ncbi.nlm.nih.gov/pubmed/25032864
http://dx.doi.org/10.1038/cddis.2014.306
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author Semba, K
Namekata, K
Kimura, A
Harada, C
Mitamura, Y
Harada, T
author_facet Semba, K
Namekata, K
Kimura, A
Harada, C
Mitamura, Y
Harada, T
author_sort Semba, K
collection PubMed
description Glaucoma is one of the leading causes of irreversible blindness that is characterized by progressive degeneration of optic nerves and retinal ganglion cells (RGCs). In the mammalian retina, excitatory amino-acid carrier 1 (EAAC1) is expressed in neural cells, including RGCs, and the loss of EAAC1 leads to RGC degeneration without elevated intraocular pressure (IOP). Brimonidine (BMD) is an α2-adrenergic receptor agonist and it is commonly used in a form of eye drops to lower IOP in glaucoma patients. Recent studies have suggested that BMD has direct protective effects on RGCs involving IOP-independent mechanisms, but it is still controversial. In the present study, we examined the effects of BMD in EAAC1-deficient (KO) mice, an animal model of normal tension glaucoma. BMD caused a small decrease in IOP, but sequential in vivo retinal imaging and electrophysiological analysis revealed that treatment with BMD was highly effective for RGC protection in EAAC1 KO mice. BMD suppressed the phosphorylation of the N-methyl-D-aspartate receptor 2B (NR2B) subunit in RGCs in EAAC1 KO mice. Furthermore, in cultured Müller glia, BMD stimulated the production of several neurotrophic factors that enhance RGC survival. These results suggest that, in addition to lowering IOP, BMD prevents glaucomatous retinal degeneration by stimulating multiple pathways including glia–neuron interactions.
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spelling pubmed-41230972014-08-15 Brimonidine prevents neurodegeneration in a mouse model of normal tension glaucoma Semba, K Namekata, K Kimura, A Harada, C Mitamura, Y Harada, T Cell Death Dis Original Article Glaucoma is one of the leading causes of irreversible blindness that is characterized by progressive degeneration of optic nerves and retinal ganglion cells (RGCs). In the mammalian retina, excitatory amino-acid carrier 1 (EAAC1) is expressed in neural cells, including RGCs, and the loss of EAAC1 leads to RGC degeneration without elevated intraocular pressure (IOP). Brimonidine (BMD) is an α2-adrenergic receptor agonist and it is commonly used in a form of eye drops to lower IOP in glaucoma patients. Recent studies have suggested that BMD has direct protective effects on RGCs involving IOP-independent mechanisms, but it is still controversial. In the present study, we examined the effects of BMD in EAAC1-deficient (KO) mice, an animal model of normal tension glaucoma. BMD caused a small decrease in IOP, but sequential in vivo retinal imaging and electrophysiological analysis revealed that treatment with BMD was highly effective for RGC protection in EAAC1 KO mice. BMD suppressed the phosphorylation of the N-methyl-D-aspartate receptor 2B (NR2B) subunit in RGCs in EAAC1 KO mice. Furthermore, in cultured Müller glia, BMD stimulated the production of several neurotrophic factors that enhance RGC survival. These results suggest that, in addition to lowering IOP, BMD prevents glaucomatous retinal degeneration by stimulating multiple pathways including glia–neuron interactions. Nature Publishing Group 2014-07 2014-07-17 /pmc/articles/PMC4123097/ /pubmed/25032864 http://dx.doi.org/10.1038/cddis.2014.306 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by/3.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/
spellingShingle Original Article
Semba, K
Namekata, K
Kimura, A
Harada, C
Mitamura, Y
Harada, T
Brimonidine prevents neurodegeneration in a mouse model of normal tension glaucoma
title Brimonidine prevents neurodegeneration in a mouse model of normal tension glaucoma
title_full Brimonidine prevents neurodegeneration in a mouse model of normal tension glaucoma
title_fullStr Brimonidine prevents neurodegeneration in a mouse model of normal tension glaucoma
title_full_unstemmed Brimonidine prevents neurodegeneration in a mouse model of normal tension glaucoma
title_short Brimonidine prevents neurodegeneration in a mouse model of normal tension glaucoma
title_sort brimonidine prevents neurodegeneration in a mouse model of normal tension glaucoma
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123097/
https://www.ncbi.nlm.nih.gov/pubmed/25032864
http://dx.doi.org/10.1038/cddis.2014.306
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