An SPM-Enriched Marine Oil Supplement Shifted Microglia Polarization toward M2, Ameliorating Retinal Degeneration in rd10 Mice

Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy causing progressive vision loss. It is accompanied by chronic and sustained inflammation, including M1 microglia activation. This study evaluated the effect of an essential fatty acid (EFA) supplement containing specialized pro...

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Autores: Olivares González, Lorena, Velasco, Sheyla, Gallego Garrido, Idoia, Esteban Medina, Marina, Puras Ochoa, Gustavo, Loucera, Carlos, Martínez Romero, Alicia, Peña Chilet, María, Pedraz Muñoz, José Luis, Rodrigo, Regina
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/59455
Acceso en línea:http://hdl.handle.net/10810/59455
Access Level:acceso abierto
Palabra clave:inherited retinal dystrophies
retinitis pigmentosa
inflammation
microglia
specialized pro-resolving mediators
oxidative stress
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spelling An SPM-Enriched Marine Oil Supplement Shifted Microglia Polarization toward M2, Ameliorating Retinal Degeneration in rd10 MiceOlivares González, LorenaVelasco, SheylaGallego Garrido, IdoiaEsteban Medina, MarinaPuras Ochoa, GustavoLoucera, CarlosMartínez Romero, AliciaPeña Chilet, MaríaPedraz Muñoz, José LuisRodrigo, Reginainherited retinal dystrophiesretinitis pigmentosainflammationmicrogliaspecialized pro-resolving mediatorsoxidative stressRetinitis pigmentosa (RP) is the most common inherited retinal dystrophy causing progressive vision loss. It is accompanied by chronic and sustained inflammation, including M1 microglia activation. This study evaluated the effect of an essential fatty acid (EFA) supplement containing specialized pro-resolving mediators (SPMs), on retinal degeneration and microglia activation in rd10 mice, a model of RP, as well as on LPS-stimulated BV2 cells. The EFA supplement was orally administered to mice from postnatal day (P)9 to P18. At P18, the electrical activity of the retina was examined by electroretinography (ERG) and innate behavior in response to light were measured. Retinal degeneration was studied via histology including the TUNEL assay and microglia immunolabeling. Microglia polarization (M1/M2) was assessed by flow cytometry, qPCR, ELISA and histology. Redox status was analyzed by measuring antioxidant enzymes and markers of oxidative damage. Interestingly, the EFA supplement ameliorated retinal dysfunction and degeneration by improving ERG recording and sensitivity to light, and reducing photoreceptor cell loss. The EFA supplement reduced inflammation and microglia activation attenuating M1 markers as well as inducing a shift to the M2 phenotype in rd10 mouse retinas and LPS-stimulated BV2 cells. It also reduced oxidative stress markers of lipid peroxidation and carbonylation. These findings could open up new therapeutic opportunities based on resolving inflammation with oral supplementation with SPMs such as the EFA supplement.This work was funded by the Spanish Ministry of Economy, Industry, and Competitiveness (MINECO), Carlos III Health Institute (ISCIII), grant numbers PI18/00252, PI20/01305, and co-funded by the European Union—European Regional Development Fund (ERDF) and the European Social Fund (FSE) ‘A way of making Europe’. It was also funded by Junta de Andalucía, grant number PE-0002-2018, CIBERER Cooperative and complementary intramural actions (ACCI) 2018, and RETINA CV. R.R. had an ISCIII Spanish National Health System (SNS) Miguel Servet Type II research contract CP15/00019. S.V. was funded by a Conselleria de Innovación, Universidades, Ciencia y Sociedad, GVA predoctoral contract (ACIF/2021/430). C.L. was funded by a Junta de Andalucía, postdoctoral contract (PAIDI2020- DOC_00350) and co-funded by the FSE 2014–2020.MDPI2023202320222023info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/59455reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoIngléshttps://www.mdpi.com/2076-3921/12/1/98info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/© 2022 by the authors.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/).oai:addi.ehu.eus:10810/594552026-06-18T09:23:17Z
dc.title.none.fl_str_mv An SPM-Enriched Marine Oil Supplement Shifted Microglia Polarization toward M2, Ameliorating Retinal Degeneration in rd10 Mice
title An SPM-Enriched Marine Oil Supplement Shifted Microglia Polarization toward M2, Ameliorating Retinal Degeneration in rd10 Mice
spellingShingle An SPM-Enriched Marine Oil Supplement Shifted Microglia Polarization toward M2, Ameliorating Retinal Degeneration in rd10 Mice
Olivares González, Lorena
inherited retinal dystrophies
retinitis pigmentosa
inflammation
microglia
specialized pro-resolving mediators
oxidative stress
title_short An SPM-Enriched Marine Oil Supplement Shifted Microglia Polarization toward M2, Ameliorating Retinal Degeneration in rd10 Mice
title_full An SPM-Enriched Marine Oil Supplement Shifted Microglia Polarization toward M2, Ameliorating Retinal Degeneration in rd10 Mice
title_fullStr An SPM-Enriched Marine Oil Supplement Shifted Microglia Polarization toward M2, Ameliorating Retinal Degeneration in rd10 Mice
title_full_unstemmed An SPM-Enriched Marine Oil Supplement Shifted Microglia Polarization toward M2, Ameliorating Retinal Degeneration in rd10 Mice
title_sort An SPM-Enriched Marine Oil Supplement Shifted Microglia Polarization toward M2, Ameliorating Retinal Degeneration in rd10 Mice
dc.creator.none.fl_str_mv Olivares González, Lorena
Velasco, Sheyla
Gallego Garrido, Idoia
Esteban Medina, Marina
Puras Ochoa, Gustavo
Loucera, Carlos
Martínez Romero, Alicia
Peña Chilet, María
Pedraz Muñoz, José Luis
Rodrigo, Regina
author Olivares González, Lorena
author_facet Olivares González, Lorena
Velasco, Sheyla
Gallego Garrido, Idoia
Esteban Medina, Marina
Puras Ochoa, Gustavo
Loucera, Carlos
Martínez Romero, Alicia
Peña Chilet, María
Pedraz Muñoz, José Luis
Rodrigo, Regina
author_role author
author2 Velasco, Sheyla
Gallego Garrido, Idoia
Esteban Medina, Marina
Puras Ochoa, Gustavo
Loucera, Carlos
Martínez Romero, Alicia
Peña Chilet, María
Pedraz Muñoz, José Luis
Rodrigo, Regina
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv inherited retinal dystrophies
retinitis pigmentosa
inflammation
microglia
specialized pro-resolving mediators
oxidative stress
topic inherited retinal dystrophies
retinitis pigmentosa
inflammation
microglia
specialized pro-resolving mediators
oxidative stress
description Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy causing progressive vision loss. It is accompanied by chronic and sustained inflammation, including M1 microglia activation. This study evaluated the effect of an essential fatty acid (EFA) supplement containing specialized pro-resolving mediators (SPMs), on retinal degeneration and microglia activation in rd10 mice, a model of RP, as well as on LPS-stimulated BV2 cells. The EFA supplement was orally administered to mice from postnatal day (P)9 to P18. At P18, the electrical activity of the retina was examined by electroretinography (ERG) and innate behavior in response to light were measured. Retinal degeneration was studied via histology including the TUNEL assay and microglia immunolabeling. Microglia polarization (M1/M2) was assessed by flow cytometry, qPCR, ELISA and histology. Redox status was analyzed by measuring antioxidant enzymes and markers of oxidative damage. Interestingly, the EFA supplement ameliorated retinal dysfunction and degeneration by improving ERG recording and sensitivity to light, and reducing photoreceptor cell loss. The EFA supplement reduced inflammation and microglia activation attenuating M1 markers as well as inducing a shift to the M2 phenotype in rd10 mouse retinas and LPS-stimulated BV2 cells. It also reduced oxidative stress markers of lipid peroxidation and carbonylation. These findings could open up new therapeutic opportunities based on resolving inflammation with oral supplementation with SPMs such as the EFA supplement.
publishDate 2022
dc.date.none.fl_str_mv 2022
2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/59455
url http://hdl.handle.net/10810/59455
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://www.mdpi.com/2076-3921/12/1/98
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
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