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Metformin Protects against NMDA-Induced Retinal Injury through the MEK/ERK Signaling Pathway in Rats
Metformin, an anti-hyperglycemic drug of the biguanide class, exerts positive effects in several non-diabetes-related diseases. In this study, we aimed to examine the protective effects of metformin against N-methyl-D-aspartic acid (NMDA)-induced excitotoxic retinal damage in rats and determine the...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123037/ https://www.ncbi.nlm.nih.gov/pubmed/33922757 http://dx.doi.org/10.3390/ijms22094439 |
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author | Watanabe, Koki Asano, Daiki Ushikubo, Hiroko Morita, Akane Mori, Asami Sakamoto, Kenji Ishii, Kunio Nakahara, Tsutomu |
author_facet | Watanabe, Koki Asano, Daiki Ushikubo, Hiroko Morita, Akane Mori, Asami Sakamoto, Kenji Ishii, Kunio Nakahara, Tsutomu |
author_sort | Watanabe, Koki |
collection | PubMed |
description | Metformin, an anti-hyperglycemic drug of the biguanide class, exerts positive effects in several non-diabetes-related diseases. In this study, we aimed to examine the protective effects of metformin against N-methyl-D-aspartic acid (NMDA)-induced excitotoxic retinal damage in rats and determine the mechanisms of its protective effects. Male Sprague–Dawley rats (7 to 9 weeks old) were used in this study. Following intravitreal injection of NMDA (200 nmol/eye), the number of neuronal cells in the ganglion cell layer and parvalbumin-positive amacrine cells decreased, whereas the number of CD45-positive leukocytes and Iba1-positive microglia increased. Metformin attenuated these NMDA-induced responses. The neuroprotective effect of metformin was abolished by compound C, an inhibitor of AMP-activated protein kinase (AMPK). The AMPK activator, AICAR, exerted a neuroprotective effect in NMDA-induced retinal injury. The MEK1/2 inhibitor, U0126, reduced the neuroprotective effect of metformin. These results suggest that metformin protects against NMDA-induced retinal neurotoxicity through activation of the AMPK and MEK/extracellular signal-regulated kinase (ERK) signaling pathways. This neuroprotective effect could be partially attributable to the inhibitory effects on inflammatory responses. |
format | Online Article Text |
id | pubmed-8123037 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81230372021-05-16 Metformin Protects against NMDA-Induced Retinal Injury through the MEK/ERK Signaling Pathway in Rats Watanabe, Koki Asano, Daiki Ushikubo, Hiroko Morita, Akane Mori, Asami Sakamoto, Kenji Ishii, Kunio Nakahara, Tsutomu Int J Mol Sci Article Metformin, an anti-hyperglycemic drug of the biguanide class, exerts positive effects in several non-diabetes-related diseases. In this study, we aimed to examine the protective effects of metformin against N-methyl-D-aspartic acid (NMDA)-induced excitotoxic retinal damage in rats and determine the mechanisms of its protective effects. Male Sprague–Dawley rats (7 to 9 weeks old) were used in this study. Following intravitreal injection of NMDA (200 nmol/eye), the number of neuronal cells in the ganglion cell layer and parvalbumin-positive amacrine cells decreased, whereas the number of CD45-positive leukocytes and Iba1-positive microglia increased. Metformin attenuated these NMDA-induced responses. The neuroprotective effect of metformin was abolished by compound C, an inhibitor of AMP-activated protein kinase (AMPK). The AMPK activator, AICAR, exerted a neuroprotective effect in NMDA-induced retinal injury. The MEK1/2 inhibitor, U0126, reduced the neuroprotective effect of metformin. These results suggest that metformin protects against NMDA-induced retinal neurotoxicity through activation of the AMPK and MEK/extracellular signal-regulated kinase (ERK) signaling pathways. This neuroprotective effect could be partially attributable to the inhibitory effects on inflammatory responses. MDPI 2021-04-23 /pmc/articles/PMC8123037/ /pubmed/33922757 http://dx.doi.org/10.3390/ijms22094439 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Watanabe, Koki Asano, Daiki Ushikubo, Hiroko Morita, Akane Mori, Asami Sakamoto, Kenji Ishii, Kunio Nakahara, Tsutomu Metformin Protects against NMDA-Induced Retinal Injury through the MEK/ERK Signaling Pathway in Rats |
title | Metformin Protects against NMDA-Induced Retinal Injury through the MEK/ERK Signaling Pathway in Rats |
title_full | Metformin Protects against NMDA-Induced Retinal Injury through the MEK/ERK Signaling Pathway in Rats |
title_fullStr | Metformin Protects against NMDA-Induced Retinal Injury through the MEK/ERK Signaling Pathway in Rats |
title_full_unstemmed | Metformin Protects against NMDA-Induced Retinal Injury through the MEK/ERK Signaling Pathway in Rats |
title_short | Metformin Protects against NMDA-Induced Retinal Injury through the MEK/ERK Signaling Pathway in Rats |
title_sort | metformin protects against nmda-induced retinal injury through the mek/erk signaling pathway in rats |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123037/ https://www.ncbi.nlm.nih.gov/pubmed/33922757 http://dx.doi.org/10.3390/ijms22094439 |
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