Etiological Roles of p75NTR in a Mouse Model of Wet Age-Related Macular Degeneration

Autores
Subirada Caldarone, Paula Virginia; Tovo, Albana; Vaglienti, María Victoria; Luna Pinto, Jose Domingo; Saragovi, Horacio Uri; Sanchez, Maria Cecilia; Anastasía, Agustín; Barcelona, Pablo Federico
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Choroidal neovascularization (CNV) is a pathological angiogenesis of the choroidal plexus of the retina and is a key feature in the wet form of age-related macular degeneration. Mononuclear phagocytic cells (MPCs) are known to accumulate in the subretinal space, generating a chronic inflammatory state that promotes the growth of the choroidal neovasculature. However, how the MPCs are recruited and activated to promote CNV pathology is not fully understood. Using genetic and pharmacological tools in a mouse model of laser-induced CNV, we demonstrate a role for the p75 neurotrophin receptor (p75NTR) in the recruitment of MPCs, in glial activation, and in vascular alterations. After laser injury, expression of p75NTR is increased in activated Muller glial cells near the CNV area in the retina and the retinal pigmented epithelium (RPE)-choroid. In p75NTR knockout mice (p75NTR KO) with CNV, there is significantly reduced recruitment of MPCs, reduced glial activation, reduced CNV area, and the retinal function is preserved, as compared to wild type mice with CNV. Notably, a single intravitreal injection of a pharmacological p75NTR antagonist in wild type mice with CNV phenocopied the results of the p75NTR KO mice. Our results demonstrate that p75NTR is etiological in the development of CNV.
Fil: Subirada Caldarone, Paula Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Tovo, Albana. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Vaglienti, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina
Fil: Luna Pinto, Jose Domingo. Fundación Ver; Argentina
Fil: Saragovi, Horacio Uri. McGill University; Canadá
Fil: Sanchez, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina
Fil: Anastasía, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina
Fil: Barcelona, Pablo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina
Materia
CHOROIDAL NEOVASCULARIZATION
MONONUCLEAR PHAGOCYTIC CELLS
NEURODEGENERATION
P75NTR
WET AGE-RELATED MACULAR DEGENERATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/226816
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/226816
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Etiological Roles of p75NTR in a Mouse Model of Wet Age-Related Macular DegenerationSubirada Caldarone, Paula VirginiaTovo, AlbanaVaglienti, María VictoriaLuna Pinto, Jose DomingoSaragovi, Horacio UriSanchez, Maria CeciliaAnastasía, AgustínBarcelona, Pablo FedericoCHOROIDAL NEOVASCULARIZATIONMONONUCLEAR PHAGOCYTIC CELLSNEURODEGENERATIONP75NTRWET AGE-RELATED MACULAR DEGENERATIONhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Choroidal neovascularization (CNV) is a pathological angiogenesis of the choroidal plexus of the retina and is a key feature in the wet form of age-related macular degeneration. Mononuclear phagocytic cells (MPCs) are known to accumulate in the subretinal space, generating a chronic inflammatory state that promotes the growth of the choroidal neovasculature. However, how the MPCs are recruited and activated to promote CNV pathology is not fully understood. Using genetic and pharmacological tools in a mouse model of laser-induced CNV, we demonstrate a role for the p75 neurotrophin receptor (p75NTR) in the recruitment of MPCs, in glial activation, and in vascular alterations. After laser injury, expression of p75NTR is increased in activated Muller glial cells near the CNV area in the retina and the retinal pigmented epithelium (RPE)-choroid. In p75NTR knockout mice (p75NTR KO) with CNV, there is significantly reduced recruitment of MPCs, reduced glial activation, reduced CNV area, and the retinal function is preserved, as compared to wild type mice with CNV. Notably, a single intravitreal injection of a pharmacological p75NTR antagonist in wild type mice with CNV phenocopied the results of the p75NTR KO mice. Our results demonstrate that p75NTR is etiological in the development of CNV.Fil: Subirada Caldarone, Paula Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Tovo, Albana. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Vaglienti, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; ArgentinaFil: Luna Pinto, Jose Domingo. Fundación Ver; ArgentinaFil: Saragovi, Horacio Uri. McGill University; CanadáFil: Sanchez, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; ArgentinaFil: Anastasía, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; ArgentinaFil: Barcelona, Pablo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; ArgentinaMDPI2023-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/226816Subirada Caldarone, Paula Virginia; Tovo, Albana; Vaglienti, María Victoria; Luna Pinto, Jose Domingo; Saragovi, Horacio Uri; et al.; Etiological Roles of p75NTR in a Mouse Model of Wet Age-Related Macular Degeneration; MDPI; Cells; 12; 2; 1-2023; 1-182073-44092073-4409CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/cells12020297info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2073-4409/12/2/297info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:17:17Zoai:ri.conicet.gov.ar:11336/226816instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:17:18.497CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Etiological Roles of p75NTR in a Mouse Model of Wet Age-Related Macular Degeneration
title Etiological Roles of p75NTR in a Mouse Model of Wet Age-Related Macular Degeneration
spellingShingle Etiological Roles of p75NTR in a Mouse Model of Wet Age-Related Macular Degeneration
Subirada Caldarone, Paula Virginia
CHOROIDAL NEOVASCULARIZATION
MONONUCLEAR PHAGOCYTIC CELLS
NEURODEGENERATION
P75NTR
WET AGE-RELATED MACULAR DEGENERATION
title_short Etiological Roles of p75NTR in a Mouse Model of Wet Age-Related Macular Degeneration
title_full Etiological Roles of p75NTR in a Mouse Model of Wet Age-Related Macular Degeneration
title_fullStr Etiological Roles of p75NTR in a Mouse Model of Wet Age-Related Macular Degeneration
title_full_unstemmed Etiological Roles of p75NTR in a Mouse Model of Wet Age-Related Macular Degeneration
title_sort Etiological Roles of p75NTR in a Mouse Model of Wet Age-Related Macular Degeneration
dc.creator.none.fl_str_mv Subirada Caldarone, Paula Virginia
Tovo, Albana
Vaglienti, María Victoria
Luna Pinto, Jose Domingo
Saragovi, Horacio Uri
Sanchez, Maria Cecilia
Anastasía, Agustín
Barcelona, Pablo Federico
author Subirada Caldarone, Paula Virginia
author_facet Subirada Caldarone, Paula Virginia
Tovo, Albana
Vaglienti, María Victoria
Luna Pinto, Jose Domingo
Saragovi, Horacio Uri
Sanchez, Maria Cecilia
Anastasía, Agustín
Barcelona, Pablo Federico
author_role author
author2 Tovo, Albana
Vaglienti, María Victoria
Luna Pinto, Jose Domingo
Saragovi, Horacio Uri
Sanchez, Maria Cecilia
Anastasía, Agustín
Barcelona, Pablo Federico
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CHOROIDAL NEOVASCULARIZATION
MONONUCLEAR PHAGOCYTIC CELLS
NEURODEGENERATION
P75NTR
WET AGE-RELATED MACULAR DEGENERATION
topic CHOROIDAL NEOVASCULARIZATION
MONONUCLEAR PHAGOCYTIC CELLS
NEURODEGENERATION
P75NTR
WET AGE-RELATED MACULAR DEGENERATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Choroidal neovascularization (CNV) is a pathological angiogenesis of the choroidal plexus of the retina and is a key feature in the wet form of age-related macular degeneration. Mononuclear phagocytic cells (MPCs) are known to accumulate in the subretinal space, generating a chronic inflammatory state that promotes the growth of the choroidal neovasculature. However, how the MPCs are recruited and activated to promote CNV pathology is not fully understood. Using genetic and pharmacological tools in a mouse model of laser-induced CNV, we demonstrate a role for the p75 neurotrophin receptor (p75NTR) in the recruitment of MPCs, in glial activation, and in vascular alterations. After laser injury, expression of p75NTR is increased in activated Muller glial cells near the CNV area in the retina and the retinal pigmented epithelium (RPE)-choroid. In p75NTR knockout mice (p75NTR KO) with CNV, there is significantly reduced recruitment of MPCs, reduced glial activation, reduced CNV area, and the retinal function is preserved, as compared to wild type mice with CNV. Notably, a single intravitreal injection of a pharmacological p75NTR antagonist in wild type mice with CNV phenocopied the results of the p75NTR KO mice. Our results demonstrate that p75NTR is etiological in the development of CNV.
Fil: Subirada Caldarone, Paula Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Tovo, Albana. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Vaglienti, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina
Fil: Luna Pinto, Jose Domingo. Fundación Ver; Argentina
Fil: Saragovi, Horacio Uri. McGill University; Canadá
Fil: Sanchez, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina
Fil: Anastasía, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina
Fil: Barcelona, Pablo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina
description Choroidal neovascularization (CNV) is a pathological angiogenesis of the choroidal plexus of the retina and is a key feature in the wet form of age-related macular degeneration. Mononuclear phagocytic cells (MPCs) are known to accumulate in the subretinal space, generating a chronic inflammatory state that promotes the growth of the choroidal neovasculature. However, how the MPCs are recruited and activated to promote CNV pathology is not fully understood. Using genetic and pharmacological tools in a mouse model of laser-induced CNV, we demonstrate a role for the p75 neurotrophin receptor (p75NTR) in the recruitment of MPCs, in glial activation, and in vascular alterations. After laser injury, expression of p75NTR is increased in activated Muller glial cells near the CNV area in the retina and the retinal pigmented epithelium (RPE)-choroid. In p75NTR knockout mice (p75NTR KO) with CNV, there is significantly reduced recruitment of MPCs, reduced glial activation, reduced CNV area, and the retinal function is preserved, as compared to wild type mice with CNV. Notably, a single intravitreal injection of a pharmacological p75NTR antagonist in wild type mice with CNV phenocopied the results of the p75NTR KO mice. Our results demonstrate that p75NTR is etiological in the development of CNV.
publishDate 2023
dc.date.none.fl_str_mv 2023-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/226816
Subirada Caldarone, Paula Virginia; Tovo, Albana; Vaglienti, María Victoria; Luna Pinto, Jose Domingo; Saragovi, Horacio Uri; et al.; Etiological Roles of p75NTR in a Mouse Model of Wet Age-Related Macular Degeneration; MDPI; Cells; 12; 2; 1-2023; 1-18
2073-4409
2073-4409
CONICET Digital
CONICET
url http://hdl.handle.net/11336/226816
identifier_str_mv Subirada Caldarone, Paula Virginia; Tovo, Albana; Vaglienti, María Victoria; Luna Pinto, Jose Domingo; Saragovi, Horacio Uri; et al.; Etiological Roles of p75NTR in a Mouse Model of Wet Age-Related Macular Degeneration; MDPI; Cells; 12; 2; 1-2023; 1-18
2073-4409
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/cells12020297
info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2073-4409/12/2/297
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
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dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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