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Minocycline prevents retinal inflammation and vascular permeability following ischemia-reperfusion injury
BACKGROUND: Many retinal diseases are associated with vascular dysfunction accompanied by neuroinflammation. We examined the ability of minocycline (Mino), a tetracycline derivative with anti-inflammatory and neuroprotective properties, to prevent vascular permeability and inflammation following ret...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3866619/ https://www.ncbi.nlm.nih.gov/pubmed/24325836 http://dx.doi.org/10.1186/1742-2094-10-149 |
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author | Abcouwer, Steven F Lin, Cheng-mao Shanmugam, Sumathi Muthusamy, Arivalagan Barber, Alistair J Antonetti, David A |
author_facet | Abcouwer, Steven F Lin, Cheng-mao Shanmugam, Sumathi Muthusamy, Arivalagan Barber, Alistair J Antonetti, David A |
author_sort | Abcouwer, Steven F |
collection | PubMed |
description | BACKGROUND: Many retinal diseases are associated with vascular dysfunction accompanied by neuroinflammation. We examined the ability of minocycline (Mino), a tetracycline derivative with anti-inflammatory and neuroprotective properties, to prevent vascular permeability and inflammation following retinal ischemia-reperfusion (IR) injury, a model of retinal neurodegeneration with breakdown of the blood-retinal barrier (BRB). METHODS: Male Sprague–Dawley rats were subjected to 45 min of pressure-induced retinal ischemia, with the contralateral eye serving as control. Rats were treated with Mino prior to and following IR. At 48 h after reperfusion, retinal gene expression, cellular inflammation, Evan’s blue dye leakage, tight junction protein organization, caspase-3 activation, and DNA fragmentation were measured. Cellular inflammation was quantified by flow-cytometric evaluation of retinal tissue using the myeloid marker CD11b and leukocyte common antigen CD45 to differentiate and quantify CD11b(+)/CD45(low) microglia, CD11b(+)/CD45(hi) myeloid leukocytes and CD11b(neg)/CD45(hi) lymphocytes. Major histocompatibility complex class II (MHCII) immunoreactivity was used to determine the inflammatory state of these cells. RESULTS: Mino treatment significantly inhibited IR-induced retinal vascular permeability and disruption of tight junction organization. Retinal IR injury significantly altered mRNA expression for 21 of 25 inflammation- and gliosis-related genes examined. Of these, Mino treatment effectively attenuated IR-induced expression of lipocalin 2 (LCN2), serpin peptidase inhibitor clade A member 3 N (SERPINA3N), TNF receptor superfamily member 12A (TNFRSF12A), monocyte chemoattractant-1 (MCP-1, CCL2) and intercellular adhesion molecule-1 (ICAM-1). A marked increase in leukostasis of both myeloid leukocytes and lymphocytes was observed following IR. Mino treatment significantly reduced retinal leukocyte numbers following IR and was particularly effective in decreasing the appearance of MHCII(+) inflammatory leukocytes. Surprisingly, Mino did not significantly inhibit retinal cell death in this model. CONCLUSIONS: IR induces a retinal neuroinflammation within hours of reperfusion characterized by inflammatory gene expression, leukocyte adhesion and invasion, and vascular permeability. Despite Mino significantly inhibiting these responses, it failed to block neurodegeneration. |
format | Online Article Text |
id | pubmed-3866619 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-38666192013-12-19 Minocycline prevents retinal inflammation and vascular permeability following ischemia-reperfusion injury Abcouwer, Steven F Lin, Cheng-mao Shanmugam, Sumathi Muthusamy, Arivalagan Barber, Alistair J Antonetti, David A J Neuroinflammation Research BACKGROUND: Many retinal diseases are associated with vascular dysfunction accompanied by neuroinflammation. We examined the ability of minocycline (Mino), a tetracycline derivative with anti-inflammatory and neuroprotective properties, to prevent vascular permeability and inflammation following retinal ischemia-reperfusion (IR) injury, a model of retinal neurodegeneration with breakdown of the blood-retinal barrier (BRB). METHODS: Male Sprague–Dawley rats were subjected to 45 min of pressure-induced retinal ischemia, with the contralateral eye serving as control. Rats were treated with Mino prior to and following IR. At 48 h after reperfusion, retinal gene expression, cellular inflammation, Evan’s blue dye leakage, tight junction protein organization, caspase-3 activation, and DNA fragmentation were measured. Cellular inflammation was quantified by flow-cytometric evaluation of retinal tissue using the myeloid marker CD11b and leukocyte common antigen CD45 to differentiate and quantify CD11b(+)/CD45(low) microglia, CD11b(+)/CD45(hi) myeloid leukocytes and CD11b(neg)/CD45(hi) lymphocytes. Major histocompatibility complex class II (MHCII) immunoreactivity was used to determine the inflammatory state of these cells. RESULTS: Mino treatment significantly inhibited IR-induced retinal vascular permeability and disruption of tight junction organization. Retinal IR injury significantly altered mRNA expression for 21 of 25 inflammation- and gliosis-related genes examined. Of these, Mino treatment effectively attenuated IR-induced expression of lipocalin 2 (LCN2), serpin peptidase inhibitor clade A member 3 N (SERPINA3N), TNF receptor superfamily member 12A (TNFRSF12A), monocyte chemoattractant-1 (MCP-1, CCL2) and intercellular adhesion molecule-1 (ICAM-1). A marked increase in leukostasis of both myeloid leukocytes and lymphocytes was observed following IR. Mino treatment significantly reduced retinal leukocyte numbers following IR and was particularly effective in decreasing the appearance of MHCII(+) inflammatory leukocytes. Surprisingly, Mino did not significantly inhibit retinal cell death in this model. CONCLUSIONS: IR induces a retinal neuroinflammation within hours of reperfusion characterized by inflammatory gene expression, leukocyte adhesion and invasion, and vascular permeability. Despite Mino significantly inhibiting these responses, it failed to block neurodegeneration. BioMed Central 2013-12-10 /pmc/articles/PMC3866619/ /pubmed/24325836 http://dx.doi.org/10.1186/1742-2094-10-149 Text en Copyright © 2013 Abcouwer et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Abcouwer, Steven F Lin, Cheng-mao Shanmugam, Sumathi Muthusamy, Arivalagan Barber, Alistair J Antonetti, David A Minocycline prevents retinal inflammation and vascular permeability following ischemia-reperfusion injury |
title | Minocycline prevents retinal inflammation and vascular permeability following ischemia-reperfusion injury |
title_full | Minocycline prevents retinal inflammation and vascular permeability following ischemia-reperfusion injury |
title_fullStr | Minocycline prevents retinal inflammation and vascular permeability following ischemia-reperfusion injury |
title_full_unstemmed | Minocycline prevents retinal inflammation and vascular permeability following ischemia-reperfusion injury |
title_short | Minocycline prevents retinal inflammation and vascular permeability following ischemia-reperfusion injury |
title_sort | minocycline prevents retinal inflammation and vascular permeability following ischemia-reperfusion injury |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3866619/ https://www.ncbi.nlm.nih.gov/pubmed/24325836 http://dx.doi.org/10.1186/1742-2094-10-149 |
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