Tlr2 gene deletion delays retinal degeneration in two genetically distinct mouse models of retinitis pigmentosa

Although considered a rare retinal dystrophy, retinitis pigmentosa (RP) is the primary cause of hereditary blindness. Given its diverse genetic etiology (>3000 mutations in >60 genes), there is an urgent need for novel treatments that target common features of the disease. TLR2 is a key activa...

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Autores: Sánchez-Cruz, Alonso, Méndez, Andrea C., Lizasoain, Ignacio, De la Villa, Pedro, De la Rosa, Enrique J., Hernández-Sánchez, Catalina
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2021
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/270826
Acesso em linha:http://hdl.handle.net/10261/270826
Access Level:Acceso aberto
Palavra-chave:Retinitis pigmentosa
Retina
TLR
TLR2
Microglia
Innate immunity
Neurodegeneration
rd10
P23H
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spelling Tlr2 gene deletion delays retinal degeneration in two genetically distinct mouse models of retinitis pigmentosaSánchez-Cruz, AlonsoMéndez, Andrea C.Lizasoain, IgnacioDe la Villa, PedroDe la Rosa, Enrique J.Hernández-Sánchez, CatalinaRetinitis pigmentosaRetinaTLRTLR2MicrogliaInnate immunityNeurodegenerationrd10P23HAlthough considered a rare retinal dystrophy, retinitis pigmentosa (RP) is the primary cause of hereditary blindness. Given its diverse genetic etiology (>3000 mutations in >60 genes), there is an urgent need for novel treatments that target common features of the disease. TLR2 is a key activator of innate immune response. To examine its role in RP progression we characterized the expression profile of Tlr2 and its adaptor molecules and the consequences of Tlr2 deletion in two genetically distinct models of RP: Pde6b (rd10) and Rho (P23H/+) mice. In both models, expression levels of Tlr2 and its adaptor molecules increased in parallel with those of the proinflammatory cytokine Il1b. In rd10 mice, deletion of a single Tlr2 allele had no effect on visual function, as evaluated by electroretinography. However, in both RP models, complete elimination of Tlr2 attenuated the loss of visual function and mitigated the loss of photoreceptor cell numbers. In Tlr2 null rd10 mice, we observed decreases in the total number of microglial cells, assessed by flow cytometry, and in the number of microglia infiltrating the photoreceptor layers. Together, these results point to TLR2 as a mutation-independent therapeutic target for RP.MINECO (SAF2016-75681-R to E.J.d.l.R. and PID2019-109506RB-100 to E.J.d.l.R. and C.H.-S.); the Instituto de Salud Carlos III (RETICS-FEDER RD16/0008/0020; FIS/PI18-00754) and co-financed by the European Regional Development Fund (ERDF) within the “Plan Estatal de Investigación Científica y Técnica y de Innovación 2017–2020” to PdlV; the Instituto de Salud Carlos IIIMolecular Diversity Preservation InternationalMinisterio de Economía y Competitividad (España)Instituto de Salud Carlos IIIConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2022202220212022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/270826reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.3390/ijms22157815Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2708262026-05-22T06:33:51Z
dc.title.none.fl_str_mv Tlr2 gene deletion delays retinal degeneration in two genetically distinct mouse models of retinitis pigmentosa
title Tlr2 gene deletion delays retinal degeneration in two genetically distinct mouse models of retinitis pigmentosa
spellingShingle Tlr2 gene deletion delays retinal degeneration in two genetically distinct mouse models of retinitis pigmentosa
Sánchez-Cruz, Alonso
Retinitis pigmentosa
Retina
TLR
TLR2
Microglia
Innate immunity
Neurodegeneration
rd10
P23H
title_short Tlr2 gene deletion delays retinal degeneration in two genetically distinct mouse models of retinitis pigmentosa
title_full Tlr2 gene deletion delays retinal degeneration in two genetically distinct mouse models of retinitis pigmentosa
title_fullStr Tlr2 gene deletion delays retinal degeneration in two genetically distinct mouse models of retinitis pigmentosa
title_full_unstemmed Tlr2 gene deletion delays retinal degeneration in two genetically distinct mouse models of retinitis pigmentosa
title_sort Tlr2 gene deletion delays retinal degeneration in two genetically distinct mouse models of retinitis pigmentosa
dc.creator.none.fl_str_mv Sánchez-Cruz, Alonso
Méndez, Andrea C.
Lizasoain, Ignacio
De la Villa, Pedro
De la Rosa, Enrique J.
Hernández-Sánchez, Catalina
author Sánchez-Cruz, Alonso
author_facet Sánchez-Cruz, Alonso
Méndez, Andrea C.
Lizasoain, Ignacio
De la Villa, Pedro
De la Rosa, Enrique J.
Hernández-Sánchez, Catalina
author_role author
author2 Méndez, Andrea C.
Lizasoain, Ignacio
De la Villa, Pedro
De la Rosa, Enrique J.
Hernández-Sánchez, Catalina
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Instituto de Salud Carlos III
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Retinitis pigmentosa
Retina
TLR
TLR2
Microglia
Innate immunity
Neurodegeneration
rd10
P23H
topic Retinitis pigmentosa
Retina
TLR
TLR2
Microglia
Innate immunity
Neurodegeneration
rd10
P23H
description Although considered a rare retinal dystrophy, retinitis pigmentosa (RP) is the primary cause of hereditary blindness. Given its diverse genetic etiology (>3000 mutations in >60 genes), there is an urgent need for novel treatments that target common features of the disease. TLR2 is a key activator of innate immune response. To examine its role in RP progression we characterized the expression profile of Tlr2 and its adaptor molecules and the consequences of Tlr2 deletion in two genetically distinct models of RP: Pde6b (rd10) and Rho (P23H/+) mice. In both models, expression levels of Tlr2 and its adaptor molecules increased in parallel with those of the proinflammatory cytokine Il1b. In rd10 mice, deletion of a single Tlr2 allele had no effect on visual function, as evaluated by electroretinography. However, in both RP models, complete elimination of Tlr2 attenuated the loss of visual function and mitigated the loss of photoreceptor cell numbers. In Tlr2 null rd10 mice, we observed decreases in the total number of microglial cells, assessed by flow cytometry, and in the number of microglia infiltrating the photoreceptor layers. Together, these results point to TLR2 as a mutation-independent therapeutic target for RP.
publishDate 2021
dc.date.none.fl_str_mv 2021
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/270826
url http://hdl.handle.net/10261/270826
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.3390/ijms22157815
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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