P2X7 and A2A receptor endogenous activation protects against neuronal death caused by CoCl2-induced photoreceptor toxicity in the zebrafish retina

Autores
Medrano, Matias; Pisera Fuster, Antonella; Bernabeu, Ramon Oscar; Faillace, Maria Paula
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Injured retinas in mammals do not regenerate and heal with loss of function. The adult retina of zebrafish self-repairs after damage by activating cell-intrinsic mechanisms, which are regulated by extrinsic signal interactions. Among relevant regulatory extrinsic systems, purinergic signaling regulates progenitor proliferation during retinogenesis and regeneration and glia proliferation in proliferative retinopathies. ATP-activated P2X7 (P2RX7) and adenosine (P1R) receptors are involved in the progression of almost all retinopathies leading to blindness. Here, we examined P2RX7 and P1R participation in the retina regenerative response induced by photoreceptor damage caused by a specific dose of CoCl2. First, we found that treatment of uninjured retinas with a potent agonist of P2RX7 (BzATP) provoked photoreceptor damage and mitotic activation of multipotent progenitors. In CoCl2-injured retinas, blockade of endogenous extracellular ATP activity on P2RX7 caused further neurodegeneration, Müller cell gliosis, progenitor proliferation, and microglia reactivity. P2RX7 inhibition in injured retinas also increased the expression of lin28a and tnfα genes, which are related to multipotent progenitor proliferation. Levels of hif1α, vegf3r, and vegfaa mRNA were enhanced by blockade of P2RX7 immediately after injury, indicating hypoxic like damage and endothelial cell growth and proliferation. Complete depletion of extracellular nucleotides with an apyrase treatment strongly potentiated cell death and progenitor proliferation induced with CoCl2. Blockade of adenosine P1 and A2A receptors (A2AR) had deleterious effects and deregulated normal timing for progenitor and precursor cell proliferation following photoreceptor damage. ATP via P2RX7 and adenosine via A2AR are survival extracellular signals key for retina regeneration in zebrafish.
Fil: Medrano, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Pisera Fuster, Antonella. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Bernabeu, Ramon Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Faillace, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Materia
A740003
ADENOSINE A2A RECEPTOR
BZATP
MICROGLIA ACTIVATION
P2X7 RECEPTOR
PHOTORECEPTOR DEATH
PROGENITOR PROLIFERATION
RRID: AB_2109952
RRID: AB_2168560
RRID: AB_2315387
RRID: AB_2338000
RRID: AB_2338685
RRID: AB_2338840
RRID: AB_2738589
RRID: AB_514483
RRID: AB_628110
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/140368

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oai_identifier_str oai:ri.conicet.gov.ar:11336/140368
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling P2X7 and A2A receptor endogenous activation protects against neuronal death caused by CoCl2-induced photoreceptor toxicity in the zebrafish retinaMedrano, MatiasPisera Fuster, AntonellaBernabeu, Ramon OscarFaillace, Maria PaulaA740003ADENOSINE A2A RECEPTORBZATPMICROGLIA ACTIVATIONP2X7 RECEPTORPHOTORECEPTOR DEATHPROGENITOR PROLIFERATIONRRID: AB_2109952RRID: AB_2168560RRID: AB_2315387RRID: AB_2338000RRID: AB_2338685RRID: AB_2338840RRID: AB_2738589RRID: AB_514483RRID: AB_628110https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Injured retinas in mammals do not regenerate and heal with loss of function. The adult retina of zebrafish self-repairs after damage by activating cell-intrinsic mechanisms, which are regulated by extrinsic signal interactions. Among relevant regulatory extrinsic systems, purinergic signaling regulates progenitor proliferation during retinogenesis and regeneration and glia proliferation in proliferative retinopathies. ATP-activated P2X7 (P2RX7) and adenosine (P1R) receptors are involved in the progression of almost all retinopathies leading to blindness. Here, we examined P2RX7 and P1R participation in the retina regenerative response induced by photoreceptor damage caused by a specific dose of CoCl2. First, we found that treatment of uninjured retinas with a potent agonist of P2RX7 (BzATP) provoked photoreceptor damage and mitotic activation of multipotent progenitors. In CoCl2-injured retinas, blockade of endogenous extracellular ATP activity on P2RX7 caused further neurodegeneration, Müller cell gliosis, progenitor proliferation, and microglia reactivity. P2RX7 inhibition in injured retinas also increased the expression of lin28a and tnfα genes, which are related to multipotent progenitor proliferation. Levels of hif1α, vegf3r, and vegfaa mRNA were enhanced by blockade of P2RX7 immediately after injury, indicating hypoxic like damage and endothelial cell growth and proliferation. Complete depletion of extracellular nucleotides with an apyrase treatment strongly potentiated cell death and progenitor proliferation induced with CoCl2. Blockade of adenosine P1 and A2A receptors (A2AR) had deleterious effects and deregulated normal timing for progenitor and precursor cell proliferation following photoreceptor damage. ATP via P2RX7 and adenosine via A2AR are survival extracellular signals key for retina regeneration in zebrafish.Fil: Medrano, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Pisera Fuster, Antonella. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Bernabeu, Ramon Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Faillace, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaWiley-liss, div John Wiley & Sons Inc.2020-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/140368Medrano, Matias; Pisera Fuster, Antonella; Bernabeu, Ramon Oscar; Faillace, Maria Paula; P2X7 and A2A receptor endogenous activation protects against neuronal death caused by CoCl2-induced photoreceptor toxicity in the zebrafish retina; Wiley-liss, div John Wiley & Sons Inc.; Journal Of Comparative Neurology; 528; 12; 1-2020; 2000-20200021-9967CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/cne.24869info:eu-repo/semantics/altIdentifier/doi/10.1002/cne.24869info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:40:37Zoai:ri.conicet.gov.ar:11336/140368instacron: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 09:40:37.946CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv P2X7 and A2A receptor endogenous activation protects against neuronal death caused by CoCl2-induced photoreceptor toxicity in the zebrafish retina
title P2X7 and A2A receptor endogenous activation protects against neuronal death caused by CoCl2-induced photoreceptor toxicity in the zebrafish retina
spellingShingle P2X7 and A2A receptor endogenous activation protects against neuronal death caused by CoCl2-induced photoreceptor toxicity in the zebrafish retina
Medrano, Matias
A740003
ADENOSINE A2A RECEPTOR
BZATP
MICROGLIA ACTIVATION
P2X7 RECEPTOR
PHOTORECEPTOR DEATH
PROGENITOR PROLIFERATION
RRID: AB_2109952
RRID: AB_2168560
RRID: AB_2315387
RRID: AB_2338000
RRID: AB_2338685
RRID: AB_2338840
RRID: AB_2738589
RRID: AB_514483
RRID: AB_628110
title_short P2X7 and A2A receptor endogenous activation protects against neuronal death caused by CoCl2-induced photoreceptor toxicity in the zebrafish retina
title_full P2X7 and A2A receptor endogenous activation protects against neuronal death caused by CoCl2-induced photoreceptor toxicity in the zebrafish retina
title_fullStr P2X7 and A2A receptor endogenous activation protects against neuronal death caused by CoCl2-induced photoreceptor toxicity in the zebrafish retina
title_full_unstemmed P2X7 and A2A receptor endogenous activation protects against neuronal death caused by CoCl2-induced photoreceptor toxicity in the zebrafish retina
title_sort P2X7 and A2A receptor endogenous activation protects against neuronal death caused by CoCl2-induced photoreceptor toxicity in the zebrafish retina
dc.creator.none.fl_str_mv Medrano, Matias
Pisera Fuster, Antonella
Bernabeu, Ramon Oscar
Faillace, Maria Paula
author Medrano, Matias
author_facet Medrano, Matias
Pisera Fuster, Antonella
Bernabeu, Ramon Oscar
Faillace, Maria Paula
author_role author
author2 Pisera Fuster, Antonella
Bernabeu, Ramon Oscar
Faillace, Maria Paula
author2_role author
author
author
dc.subject.none.fl_str_mv A740003
ADENOSINE A2A RECEPTOR
BZATP
MICROGLIA ACTIVATION
P2X7 RECEPTOR
PHOTORECEPTOR DEATH
PROGENITOR PROLIFERATION
RRID: AB_2109952
RRID: AB_2168560
RRID: AB_2315387
RRID: AB_2338000
RRID: AB_2338685
RRID: AB_2338840
RRID: AB_2738589
RRID: AB_514483
RRID: AB_628110
topic A740003
ADENOSINE A2A RECEPTOR
BZATP
MICROGLIA ACTIVATION
P2X7 RECEPTOR
PHOTORECEPTOR DEATH
PROGENITOR PROLIFERATION
RRID: AB_2109952
RRID: AB_2168560
RRID: AB_2315387
RRID: AB_2338000
RRID: AB_2338685
RRID: AB_2338840
RRID: AB_2738589
RRID: AB_514483
RRID: AB_628110
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Injured retinas in mammals do not regenerate and heal with loss of function. The adult retina of zebrafish self-repairs after damage by activating cell-intrinsic mechanisms, which are regulated by extrinsic signal interactions. Among relevant regulatory extrinsic systems, purinergic signaling regulates progenitor proliferation during retinogenesis and regeneration and glia proliferation in proliferative retinopathies. ATP-activated P2X7 (P2RX7) and adenosine (P1R) receptors are involved in the progression of almost all retinopathies leading to blindness. Here, we examined P2RX7 and P1R participation in the retina regenerative response induced by photoreceptor damage caused by a specific dose of CoCl2. First, we found that treatment of uninjured retinas with a potent agonist of P2RX7 (BzATP) provoked photoreceptor damage and mitotic activation of multipotent progenitors. In CoCl2-injured retinas, blockade of endogenous extracellular ATP activity on P2RX7 caused further neurodegeneration, Müller cell gliosis, progenitor proliferation, and microglia reactivity. P2RX7 inhibition in injured retinas also increased the expression of lin28a and tnfα genes, which are related to multipotent progenitor proliferation. Levels of hif1α, vegf3r, and vegfaa mRNA were enhanced by blockade of P2RX7 immediately after injury, indicating hypoxic like damage and endothelial cell growth and proliferation. Complete depletion of extracellular nucleotides with an apyrase treatment strongly potentiated cell death and progenitor proliferation induced with CoCl2. Blockade of adenosine P1 and A2A receptors (A2AR) had deleterious effects and deregulated normal timing for progenitor and precursor cell proliferation following photoreceptor damage. ATP via P2RX7 and adenosine via A2AR are survival extracellular signals key for retina regeneration in zebrafish.
Fil: Medrano, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Pisera Fuster, Antonella. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Bernabeu, Ramon Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Faillace, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
description Injured retinas in mammals do not regenerate and heal with loss of function. The adult retina of zebrafish self-repairs after damage by activating cell-intrinsic mechanisms, which are regulated by extrinsic signal interactions. Among relevant regulatory extrinsic systems, purinergic signaling regulates progenitor proliferation during retinogenesis and regeneration and glia proliferation in proliferative retinopathies. ATP-activated P2X7 (P2RX7) and adenosine (P1R) receptors are involved in the progression of almost all retinopathies leading to blindness. Here, we examined P2RX7 and P1R participation in the retina regenerative response induced by photoreceptor damage caused by a specific dose of CoCl2. First, we found that treatment of uninjured retinas with a potent agonist of P2RX7 (BzATP) provoked photoreceptor damage and mitotic activation of multipotent progenitors. In CoCl2-injured retinas, blockade of endogenous extracellular ATP activity on P2RX7 caused further neurodegeneration, Müller cell gliosis, progenitor proliferation, and microglia reactivity. P2RX7 inhibition in injured retinas also increased the expression of lin28a and tnfα genes, which are related to multipotent progenitor proliferation. Levels of hif1α, vegf3r, and vegfaa mRNA were enhanced by blockade of P2RX7 immediately after injury, indicating hypoxic like damage and endothelial cell growth and proliferation. Complete depletion of extracellular nucleotides with an apyrase treatment strongly potentiated cell death and progenitor proliferation induced with CoCl2. Blockade of adenosine P1 and A2A receptors (A2AR) had deleterious effects and deregulated normal timing for progenitor and precursor cell proliferation following photoreceptor damage. ATP via P2RX7 and adenosine via A2AR are survival extracellular signals key for retina regeneration in zebrafish.
publishDate 2020
dc.date.none.fl_str_mv 2020-01
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/11336/140368
Medrano, Matias; Pisera Fuster, Antonella; Bernabeu, Ramon Oscar; Faillace, Maria Paula; P2X7 and A2A receptor endogenous activation protects against neuronal death caused by CoCl2-induced photoreceptor toxicity in the zebrafish retina; Wiley-liss, div John Wiley & Sons Inc.; Journal Of Comparative Neurology; 528; 12; 1-2020; 2000-2020
0021-9967
CONICET Digital
CONICET
url http://hdl.handle.net/11336/140368
identifier_str_mv Medrano, Matias; Pisera Fuster, Antonella; Bernabeu, Ramon Oscar; Faillace, Maria Paula; P2X7 and A2A receptor endogenous activation protects against neuronal death caused by CoCl2-induced photoreceptor toxicity in the zebrafish retina; Wiley-liss, div John Wiley & Sons Inc.; Journal Of Comparative Neurology; 528; 12; 1-2020; 2000-2020
0021-9967
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/cne.24869
info:eu-repo/semantics/altIdentifier/doi/10.1002/cne.24869
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley-liss, div John Wiley & Sons Inc.
publisher.none.fl_str_mv Wiley-liss, div John Wiley & Sons Inc.
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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