Effects of the topical administration of semaglutide on retinal neuroinflammation and vascular leakage in experimental diabetes

Background: An unexpected increase in the rate of severe diabetic retinopathy was observed in the Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN)-6 clinical trial. Although this effect was attributed to a rapid decrease in blood glucose levels, a direct deleterious effect of semaglutide on th...

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Autores: Simó Canonge, Rafael|||0000-0003-0475-3096, Bogdanov, Patricia|||0000-0003-0669-4958, Ramos, Hugo|||0000-0001-6443-7576, Huerta, Jordi|||0000-0002-9908-8051, Simó-Servat, Olga|||0000-0003-3483-652X, Hernández, Cristina|||0000-0002-3109-1721
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:256708
Acceso en línea:https://ddd.uab.cat/record/256708
https://dx.doi.org/urn:doi:10.3390/biomedicines9080926
Access Level:acceso abierto
Palabra clave:Diabetic retinopathy
Semaglutide
Retina
Db/db mouse
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spelling Effects of the topical administration of semaglutide on retinal neuroinflammation and vascular leakage in experimental diabetesSimó Canonge, Rafael|||0000-0003-0475-3096Bogdanov, Patricia|||0000-0003-0669-4958Ramos, Hugo|||0000-0001-6443-7576Huerta, Jordi|||0000-0002-9908-8051Simó-Servat, Olga|||0000-0003-3483-652XHernández, Cristina|||0000-0002-3109-1721Diabetic retinopathySemaglutideRetinaDb/db mouseBackground: An unexpected increase in the rate of severe diabetic retinopathy was observed in the Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN)-6 clinical trial. Although this effect was attributed to a rapid decrease in blood glucose levels, a direct deleterious effect of semaglutide on the retina could not be ruled out. In order to shed light on this issue, we have performed a study aimed at testing the direct effect of semaglutide administered by eye drops on retinal neuroinflammation and microvascular abnormalities using the db/db mouse model. Methods: Eye drops containing semaglutide (0.33 mg/mL; 5 µL once/daily) or vehicle (PBS; 5 µL once daily) were administered for 15 days. Results: We found that semaglutide significantly reduced glial activation, as well as the retinal expression of Nuclear factor kB (NF-κB), proinflammatory cytokines (IL-1β, IL-6, IL-18) and Intercellular Adhesion Molecule (ICAM)-1. In addition, semaglutide prevented the apoptosis of cells from the retinal ganglion layer and activated the protein kinase B (AKT) pathway. Finally, a dramatic decrease in vascular leakage was observed in db/db mice treated with semaglu-tide. All these findings were observed without any change in blood glucose levels and, therefore, can be directly attributed to semaglutide. Conclusions: These experimental findings point to a beneficial rather than a deleterious effect of semaglutide on the retina of subjects with diabetes. 0926.Universitat Autònoma de Barcelona 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/256708https://dx.doi.org/urn:doi:10.3390/biomedicines9080926reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 201629-10Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI16/00541Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI19/01215Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2016-77784open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2567082026-06-06T12:50:31Z
dc.title.none.fl_str_mv Effects of the topical administration of semaglutide on retinal neuroinflammation and vascular leakage in experimental diabetes
title Effects of the topical administration of semaglutide on retinal neuroinflammation and vascular leakage in experimental diabetes
spellingShingle Effects of the topical administration of semaglutide on retinal neuroinflammation and vascular leakage in experimental diabetes
Simó Canonge, Rafael|||0000-0003-0475-3096
Diabetic retinopathy
Semaglutide
Retina
Db/db mouse
title_short Effects of the topical administration of semaglutide on retinal neuroinflammation and vascular leakage in experimental diabetes
title_full Effects of the topical administration of semaglutide on retinal neuroinflammation and vascular leakage in experimental diabetes
title_fullStr Effects of the topical administration of semaglutide on retinal neuroinflammation and vascular leakage in experimental diabetes
title_full_unstemmed Effects of the topical administration of semaglutide on retinal neuroinflammation and vascular leakage in experimental diabetes
title_sort Effects of the topical administration of semaglutide on retinal neuroinflammation and vascular leakage in experimental diabetes
dc.creator.none.fl_str_mv Simó Canonge, Rafael|||0000-0003-0475-3096
Bogdanov, Patricia|||0000-0003-0669-4958
Ramos, Hugo|||0000-0001-6443-7576
Huerta, Jordi|||0000-0002-9908-8051
Simó-Servat, Olga|||0000-0003-3483-652X
Hernández, Cristina|||0000-0002-3109-1721
author Simó Canonge, Rafael|||0000-0003-0475-3096
author_facet Simó Canonge, Rafael|||0000-0003-0475-3096
Bogdanov, Patricia|||0000-0003-0669-4958
Ramos, Hugo|||0000-0001-6443-7576
Huerta, Jordi|||0000-0002-9908-8051
Simó-Servat, Olga|||0000-0003-3483-652X
Hernández, Cristina|||0000-0002-3109-1721
author_role author
author2 Bogdanov, Patricia|||0000-0003-0669-4958
Ramos, Hugo|||0000-0001-6443-7576
Huerta, Jordi|||0000-0002-9908-8051
Simó-Servat, Olga|||0000-0003-3483-652X
Hernández, Cristina|||0000-0002-3109-1721
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Diabetic retinopathy
Semaglutide
Retina
Db/db mouse
topic Diabetic retinopathy
Semaglutide
Retina
Db/db mouse
description Background: An unexpected increase in the rate of severe diabetic retinopathy was observed in the Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN)-6 clinical trial. Although this effect was attributed to a rapid decrease in blood glucose levels, a direct deleterious effect of semaglutide on the retina could not be ruled out. In order to shed light on this issue, we have performed a study aimed at testing the direct effect of semaglutide administered by eye drops on retinal neuroinflammation and microvascular abnormalities using the db/db mouse model. Methods: Eye drops containing semaglutide (0.33 mg/mL; 5 µL once/daily) or vehicle (PBS; 5 µL once daily) were administered for 15 days. Results: We found that semaglutide significantly reduced glial activation, as well as the retinal expression of Nuclear factor kB (NF-κB), proinflammatory cytokines (IL-1β, IL-6, IL-18) and Intercellular Adhesion Molecule (ICAM)-1. In addition, semaglutide prevented the apoptosis of cells from the retinal ganglion layer and activated the protein kinase B (AKT) pathway. Finally, a dramatic decrease in vascular leakage was observed in db/db mice treated with semaglu-tide. All these findings were observed without any change in blood glucose levels and, therefore, can be directly attributed to semaglutide. Conclusions: These experimental findings point to a beneficial rather than a deleterious effect of semaglutide on the retina of subjects with diabetes. 0926.
publishDate 2021
dc.date.none.fl_str_mv 2
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/256708
https://dx.doi.org/urn:doi:10.3390/biomedicines9080926
url https://ddd.uab.cat/record/256708
https://dx.doi.org/urn:doi:10.3390/biomedicines9080926
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 201629-10
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI16/00541
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI19/01215
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2016-77784
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
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
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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