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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/140368
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oai:ri.conicet.gov.ar:11336/140368 |
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CONICET Digital (CONICET) |
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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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1844613285928763392 |
score |
13.070432 |