Autophagy resolves early retinal inflammation in Igf1-deficient mice
Insulin-like growth factor-1 (IGF-1) is a growth factor with differentiating, anti-apoptotic and metabolic functions in the periphery, and anti-inflammatory properties in the nervous system. Mice that have mutations in the Igf1 gene, rendering the gene product inactive (Igf1(-/-)), present with age-...
| Autores: | , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | Universidad de Cantabria (UC) |
| Repositorio: | UCrea Repositorio Abierto de la Universidad de Cantabria |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.unican.es:10902/9221 |
| Acceso en línea: | http://hdl.handle.net/10902/9221 |
| Access Level: | acceso abierto |
| Palabra clave: | Autophagy IGF-1 Neurodegeneration Neuroinflammation Retina |
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Autophagy resolves early retinal inflammation in Igf1-deficient miceArroba, AIRodríguez de la Rosa, L.Murillo Cuesta, S.Vaquero Villanueva, L.Hurlé González, Juan M.|||0000-0002-4685-025XVarela Nieto, I.Valverde, AMAutophagyIGF-1NeurodegenerationNeuroinflammationRetinaInsulin-like growth factor-1 (IGF-1) is a growth factor with differentiating, anti-apoptotic and metabolic functions in the periphery, and anti-inflammatory properties in the nervous system. Mice that have mutations in the Igf1 gene, rendering the gene product inactive (Igf1(-/-)), present with age-related visual loss accompanied by structural alterations in the first synapses of the retinal pathway. Recent advances have revealed a crucial role of autophagy in immunity and inflammation. Keeping in mind this close relationship, we aimed to decipher these processes in the context of the defects that occur during ageing in the retina of Igf1(-/-) mice. Tnfa and Il1b mRNAs, and phosphorylation of JNK and p38 MAPK were elevated in the retinas of 6- and 12-month old Igf1(-/-) mice compared to those in age-matched Igf1(+/+) controls. In 6-month-old Igf1(-/-) retinas, increased mRNA levels of the autophagy mediators Becn1, Atg9, Atg5 and Atg4, decreased p62 (also known as SQSTM1) protein expression together with an increased LC3-II:LC3-I ratio reflected active autophagic flux. However, in retinas from 12-month-old Igf1(-/-) mice, Nlrp3 mRNA, processing of the IL1β pro-form and immunostaining of active caspase-1 were elevated compared to those in age-matched Igf1(+/+) controls, suggesting activation of the inflammasome. This effect concurred with accumulation of autophagosomes and decreased autophagic flux in the retina. Microglia localization and status of activation in the retinas of 12-month-old Igf1(+/+) and Igf1(-/-) mice, analyzed by immunostaining of Cd11b and Iba-1, showed a specific distribution pattern in the outer plexiform layer (OPL), inner plexiform layer (IPL) and inner nuclear layer (INL), and revealed an increased number of activated microglia cells in the retina of 12-month-old blind Igf1(-/-) mice. Moreover, reactive gliosis was exclusively detected in the retinas from 12-month-old blind Igf1(-/-) mice. In conclusion, this study provides new evidence in a mouse model of IGF-1 deficiency that autophagy is an adaptive response that might confer protection against persistent inflammation in the retina during ageingCompany of Biologists Ltd.Universidad de Cantabria20162016-01-01journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articlehttp://hdl.handle.net/10902/9221Dis Model Mech. 2016 Sep 1;9(9):965-74reponame:UCrea Repositorio Abierto de la Universidad de Cantabriainstname:Universidad de Cantabria (UC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución-NoComercial-SinDerivadas 3.0 Españahttp://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:repositorio.unican.es:10902/92212026-06-02T12:39:31Z |
| dc.title.none.fl_str_mv |
Autophagy resolves early retinal inflammation in Igf1-deficient mice |
| title |
Autophagy resolves early retinal inflammation in Igf1-deficient mice |
| spellingShingle |
Autophagy resolves early retinal inflammation in Igf1-deficient mice Arroba, AI Autophagy IGF-1 Neurodegeneration Neuroinflammation Retina |
| title_short |
Autophagy resolves early retinal inflammation in Igf1-deficient mice |
| title_full |
Autophagy resolves early retinal inflammation in Igf1-deficient mice |
| title_fullStr |
Autophagy resolves early retinal inflammation in Igf1-deficient mice |
| title_full_unstemmed |
Autophagy resolves early retinal inflammation in Igf1-deficient mice |
| title_sort |
Autophagy resolves early retinal inflammation in Igf1-deficient mice |
| dc.creator.none.fl_str_mv |
Arroba, AI Rodríguez de la Rosa, L. Murillo Cuesta, S. Vaquero Villanueva, L. Hurlé González, Juan M.|||0000-0002-4685-025X Varela Nieto, I. Valverde, AM |
| author |
Arroba, AI |
| author_facet |
Arroba, AI Rodríguez de la Rosa, L. Murillo Cuesta, S. Vaquero Villanueva, L. Hurlé González, Juan M.|||0000-0002-4685-025X Varela Nieto, I. Valverde, AM |
| author_role |
author |
| author2 |
Rodríguez de la Rosa, L. Murillo Cuesta, S. Vaquero Villanueva, L. Hurlé González, Juan M.|||0000-0002-4685-025X Varela Nieto, I. Valverde, AM |
| author2_role |
author author author author author author |
| dc.contributor.none.fl_str_mv |
Universidad de Cantabria |
| dc.subject.none.fl_str_mv |
Autophagy IGF-1 Neurodegeneration Neuroinflammation Retina |
| topic |
Autophagy IGF-1 Neurodegeneration Neuroinflammation Retina |
| description |
Insulin-like growth factor-1 (IGF-1) is a growth factor with differentiating, anti-apoptotic and metabolic functions in the periphery, and anti-inflammatory properties in the nervous system. Mice that have mutations in the Igf1 gene, rendering the gene product inactive (Igf1(-/-)), present with age-related visual loss accompanied by structural alterations in the first synapses of the retinal pathway. Recent advances have revealed a crucial role of autophagy in immunity and inflammation. Keeping in mind this close relationship, we aimed to decipher these processes in the context of the defects that occur during ageing in the retina of Igf1(-/-) mice. Tnfa and Il1b mRNAs, and phosphorylation of JNK and p38 MAPK were elevated in the retinas of 6- and 12-month old Igf1(-/-) mice compared to those in age-matched Igf1(+/+) controls. In 6-month-old Igf1(-/-) retinas, increased mRNA levels of the autophagy mediators Becn1, Atg9, Atg5 and Atg4, decreased p62 (also known as SQSTM1) protein expression together with an increased LC3-II:LC3-I ratio reflected active autophagic flux. However, in retinas from 12-month-old Igf1(-/-) mice, Nlrp3 mRNA, processing of the IL1β pro-form and immunostaining of active caspase-1 were elevated compared to those in age-matched Igf1(+/+) controls, suggesting activation of the inflammasome. This effect concurred with accumulation of autophagosomes and decreased autophagic flux in the retina. Microglia localization and status of activation in the retinas of 12-month-old Igf1(+/+) and Igf1(-/-) mice, analyzed by immunostaining of Cd11b and Iba-1, showed a specific distribution pattern in the outer plexiform layer (OPL), inner plexiform layer (IPL) and inner nuclear layer (INL), and revealed an increased number of activated microglia cells in the retina of 12-month-old blind Igf1(-/-) mice. Moreover, reactive gliosis was exclusively detected in the retinas from 12-month-old blind Igf1(-/-) mice. In conclusion, this study provides new evidence in a mouse model of IGF-1 deficiency that autophagy is an adaptive response that might confer protection against persistent inflammation in the retina during ageing |
| publishDate |
2016 |
| dc.date.none.fl_str_mv |
2016 2016-01-01 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 NA http://purl.org/coar/version/c_be7fb7dd8ff6fe43 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10902/9221 |
| url |
http://hdl.handle.net/10902/9221 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Atribución-NoComercial-SinDerivadas 3.0 España http://creativecommons.org/licenses/by-nc-nd/3.0/es/ |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Atribución-NoComercial-SinDerivadas 3.0 España http://creativecommons.org/licenses/by-nc-nd/3.0/es/ |
| eu_rights_str_mv |
openAccess |
| dc.publisher.none.fl_str_mv |
Company of Biologists Ltd. |
| publisher.none.fl_str_mv |
Company of Biologists Ltd. |
| dc.source.none.fl_str_mv |
Dis Model Mech. 2016 Sep 1;9(9):965-74 reponame:UCrea Repositorio Abierto de la Universidad de Cantabria instname:Universidad de Cantabria (UC) |
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Universidad de Cantabria (UC) |
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UCrea Repositorio Abierto de la Universidad de Cantabria |
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UCrea Repositorio Abierto de la Universidad de Cantabria |
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|
| repository.mail.fl_str_mv |
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15,300724 |