Dual-Acting Antiangiogenic Gene Therapy Reduces Inflammation and Regresses Neovascularization in Diabetic Mouse Retina

Detalhes bibliográficos
Autor(a) principal: Araújo, Rute S.
Data de Publicação: 2020
Outros Autores: Bitoque, Diogo B., Silva, Gabriela A.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/105767
Resumo: The authors acknowledge the financial support of Fundação para a Ciência e a Tecnologia (SFRH/BD/114051/2016 individual fellowship to R.S.A.), Projetos de Investigação Científica e Desenvolvimento Tecnológico (IC&DT, grant 02/SAICT/2017/028121 to G.A.S.), and the Marie Curie Reintegration Grant (PIRG-GA-2009-249314 to G.A.S.) under the FP7 program. iNOVA4Health, UID/Multi/04462/ 2013, a program financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência through national funds and co-funded by FEDER under the PT2020 Partnership Agreement, is also acknowledged.
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spelling Dual-Acting Antiangiogenic Gene Therapy Reduces Inflammation and Regresses Neovascularization in Diabetic Mouse Retinadiabetic retinopathygene therapyneovascularizationpigment epithelium-derived factorplacental growth factorretinaretinal pigment epitheliumsubretinal deliveryvascular plexusMolecular MedicineDrug DiscoverySDG 3 - Good Health and Well-beingThe authors acknowledge the financial support of Fundação para a Ciência e a Tecnologia (SFRH/BD/114051/2016 individual fellowship to R.S.A.), Projetos de Investigação Científica e Desenvolvimento Tecnológico (IC&DT, grant 02/SAICT/2017/028121 to G.A.S.), and the Marie Curie Reintegration Grant (PIRG-GA-2009-249314 to G.A.S.) under the FP7 program. iNOVA4Health, UID/Multi/04462/ 2013, a program financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência through national funds and co-funded by FEDER under the PT2020 Partnership Agreement, is also acknowledged.Intravitreal injections of anti-vascular endothelial growth factor drugs have become the gold standard treatment for diabetic retinopathy (DR). However, several patients are classified as non-responders or poor responders to treatment. Therefore, it is essential to study alternative target molecules. We have previously shown that the progression of DR in the Ins2Akita mouse reflects the imbalance between pro- and anti-angiogenic molecules found in the human retina. We report, for the first time, the therapeutic potential of a dual-acting antiangiogenic non-viral gene therapy. We have used an expressing vector encoding both the pigment epithelium-derived factor gene and a short hairpin RNA (shRNA) targeted to the placental growth factor to restore the balance between these factors in the retina. Twenty-one days after a single subretinal injection, we observed a marked decrease in the inflammatory response in the neural retina and in the retinal pigment epithelium, together with reduced vascular retinal permeability in the treated diabetic mouse. These results were accompanied by the restoration of the retinal capillary network and regression of neovascularization, with significant improvement of DR hallmarks. Concomitant with the favorable therapeutic effects, this approach did not affect retinal ganglion cells. Hence our results provide evidence toward the use of this approach in DR treatment.Centro de Estudos de Doenças Crónicas (CEDOC)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNAraújo, Rute S.Bitoque, Diogo B.Silva, Gabriela A.2020-10-17T00:19:40Z2020-12-042020-12-04T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article11application/pdfhttp://hdl.handle.net/10362/105767engPURE: 20127419https://doi.org/10.1016/j.omtn.2020.08.036info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:51:00Zoai:run.unl.pt:10362/105767Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:40:35.570656Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Dual-Acting Antiangiogenic Gene Therapy Reduces Inflammation and Regresses Neovascularization in Diabetic Mouse Retina
title Dual-Acting Antiangiogenic Gene Therapy Reduces Inflammation and Regresses Neovascularization in Diabetic Mouse Retina
spellingShingle Dual-Acting Antiangiogenic Gene Therapy Reduces Inflammation and Regresses Neovascularization in Diabetic Mouse Retina
Araújo, Rute S.
diabetic retinopathy
gene therapy
neovascularization
pigment epithelium-derived factor
placental growth factor
retina
retinal pigment epithelium
subretinal delivery
vascular plexus
Molecular Medicine
Drug Discovery
SDG 3 - Good Health and Well-being
title_short Dual-Acting Antiangiogenic Gene Therapy Reduces Inflammation and Regresses Neovascularization in Diabetic Mouse Retina
title_full Dual-Acting Antiangiogenic Gene Therapy Reduces Inflammation and Regresses Neovascularization in Diabetic Mouse Retina
title_fullStr Dual-Acting Antiangiogenic Gene Therapy Reduces Inflammation and Regresses Neovascularization in Diabetic Mouse Retina
title_full_unstemmed Dual-Acting Antiangiogenic Gene Therapy Reduces Inflammation and Regresses Neovascularization in Diabetic Mouse Retina
title_sort Dual-Acting Antiangiogenic Gene Therapy Reduces Inflammation and Regresses Neovascularization in Diabetic Mouse Retina
author Araújo, Rute S.
author_facet Araújo, Rute S.
Bitoque, Diogo B.
Silva, Gabriela A.
author_role author
author2 Bitoque, Diogo B.
Silva, Gabriela A.
author2_role author
author
dc.contributor.none.fl_str_mv Centro de Estudos de Doenças Crónicas (CEDOC)
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
RUN
dc.contributor.author.fl_str_mv Araújo, Rute S.
Bitoque, Diogo B.
Silva, Gabriela A.
dc.subject.por.fl_str_mv diabetic retinopathy
gene therapy
neovascularization
pigment epithelium-derived factor
placental growth factor
retina
retinal pigment epithelium
subretinal delivery
vascular plexus
Molecular Medicine
Drug Discovery
SDG 3 - Good Health and Well-being
topic diabetic retinopathy
gene therapy
neovascularization
pigment epithelium-derived factor
placental growth factor
retina
retinal pigment epithelium
subretinal delivery
vascular plexus
Molecular Medicine
Drug Discovery
SDG 3 - Good Health and Well-being
description The authors acknowledge the financial support of Fundação para a Ciência e a Tecnologia (SFRH/BD/114051/2016 individual fellowship to R.S.A.), Projetos de Investigação Científica e Desenvolvimento Tecnológico (IC&DT, grant 02/SAICT/2017/028121 to G.A.S.), and the Marie Curie Reintegration Grant (PIRG-GA-2009-249314 to G.A.S.) under the FP7 program. iNOVA4Health, UID/Multi/04462/ 2013, a program financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência through national funds and co-funded by FEDER under the PT2020 Partnership Agreement, is also acknowledged.
publishDate 2020
dc.date.none.fl_str_mv 2020-10-17T00:19:40Z
2020-12-04
2020-12-04T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/105767
url http://hdl.handle.net/10362/105767
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv PURE: 20127419
https://doi.org/10.1016/j.omtn.2020.08.036
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 11
application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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