Choroidal and retinal structural, cellular and vascular changes in a rat model of Type 2 diabetes

Detalhes bibliográficos
Autor(a) principal: Campos, António
Data de Publicação: 2020
Outros Autores: Martins, João, Campos, Elisa J., Silva, Rufino, Ambrósio, António Francisco
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10316/105816
https://doi.org/10.1016/j.biopha.2020.110811
Resumo: Increasing evidence points to inflammation as a key factor in the pathogenesis of diabetic retinopathy (DR). Choroidal changes in diabetes have been reported and several attempts were made to validate in vivo choroidal thickness (CT) as a marker of retinopathy. We aimed to study choroidal and retinal changes associated with retinopathy in an animal model of spontaneous Type 2 diabetes, Goto-Kakizaki (GK) rats. Sclerochoroidal whole mounts and cryosections were prepared from 52-week-old GK and age-matched control Wistar Han rats. CT was measured by optical coherence tomography. Microglia reactivity, pericyte and endothelial cells distribution, and immunoreactivity of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) were evaluated by immunofluorescence. Choroidal vessels were visualized by direct perfusion with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil). Choroidal vascular density was evaluated by fluorescence microscopy. GK rats had increased CT (58.40 ± 1.15 μm versus 50.90 ± 1.58 μm, p < 0.001), reduced vascular density of the choriocapillaris (CC) (p = 0.045), increased Iba1+ cells density in the outer retina (p = 0.003) and increased VEGFR2 immunoreactivity in most retinal layers (p = 0.021 to 0.037). Choroidal microglial cells and pericytes showed polarity in their distribution, sparing the innermost choroid. This cell-free gap in the inner choroid was more pronounced in GK rats. In summary, GK rats have increased CT with decreased vascular density in the innermost choroid, increased VEGFR2 immunoreactivity in the retina and increased Iba1+ cells density in the outer retina.
id RCAP_42c1985446a314f362a671d49f159ea8
oai_identifier_str oai:estudogeral.uc.pt:10316/105816
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling Choroidal and retinal structural, cellular and vascular changes in a rat model of Type 2 diabetesType 2 diabetesChoroid RetinaChoroidal thicknessMicrogliaVEGFR2Increasing evidence points to inflammation as a key factor in the pathogenesis of diabetic retinopathy (DR). Choroidal changes in diabetes have been reported and several attempts were made to validate in vivo choroidal thickness (CT) as a marker of retinopathy. We aimed to study choroidal and retinal changes associated with retinopathy in an animal model of spontaneous Type 2 diabetes, Goto-Kakizaki (GK) rats. Sclerochoroidal whole mounts and cryosections were prepared from 52-week-old GK and age-matched control Wistar Han rats. CT was measured by optical coherence tomography. Microglia reactivity, pericyte and endothelial cells distribution, and immunoreactivity of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) were evaluated by immunofluorescence. Choroidal vessels were visualized by direct perfusion with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil). Choroidal vascular density was evaluated by fluorescence microscopy. GK rats had increased CT (58.40 ± 1.15 μm versus 50.90 ± 1.58 μm, p < 0.001), reduced vascular density of the choriocapillaris (CC) (p = 0.045), increased Iba1+ cells density in the outer retina (p = 0.003) and increased VEGFR2 immunoreactivity in most retinal layers (p = 0.021 to 0.037). Choroidal microglial cells and pericytes showed polarity in their distribution, sparing the innermost choroid. This cell-free gap in the inner choroid was more pronounced in GK rats. In summary, GK rats have increased CT with decreased vascular density in the innermost choroid, increased VEGFR2 immunoreactivity in the retina and increased Iba1+ cells density in the outer retina.Elsevier2020-12info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/105816http://hdl.handle.net/10316/105816https://doi.org/10.1016/j.biopha.2020.110811eng07533322330699671950-6007Campos, AntónioMartins, JoãoCampos, Elisa J.Silva, RufinoAmbrósio, António Franciscoinfo: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:RCAAP2023-03-09T21:31:10Zoai:estudogeral.uc.pt:10316/105816Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:22:18.959632Repositório 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 Choroidal and retinal structural, cellular and vascular changes in a rat model of Type 2 diabetes
title Choroidal and retinal structural, cellular and vascular changes in a rat model of Type 2 diabetes
spellingShingle Choroidal and retinal structural, cellular and vascular changes in a rat model of Type 2 diabetes
Campos, António
Type 2 diabetes
Choroid Retina
Choroidal thickness
Microglia
VEGFR2
title_short Choroidal and retinal structural, cellular and vascular changes in a rat model of Type 2 diabetes
title_full Choroidal and retinal structural, cellular and vascular changes in a rat model of Type 2 diabetes
title_fullStr Choroidal and retinal structural, cellular and vascular changes in a rat model of Type 2 diabetes
title_full_unstemmed Choroidal and retinal structural, cellular and vascular changes in a rat model of Type 2 diabetes
title_sort Choroidal and retinal structural, cellular and vascular changes in a rat model of Type 2 diabetes
author Campos, António
author_facet Campos, António
Martins, João
Campos, Elisa J.
Silva, Rufino
Ambrósio, António Francisco
author_role author
author2 Martins, João
Campos, Elisa J.
Silva, Rufino
Ambrósio, António Francisco
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Campos, António
Martins, João
Campos, Elisa J.
Silva, Rufino
Ambrósio, António Francisco
dc.subject.por.fl_str_mv Type 2 diabetes
Choroid Retina
Choroidal thickness
Microglia
VEGFR2
topic Type 2 diabetes
Choroid Retina
Choroidal thickness
Microglia
VEGFR2
description Increasing evidence points to inflammation as a key factor in the pathogenesis of diabetic retinopathy (DR). Choroidal changes in diabetes have been reported and several attempts were made to validate in vivo choroidal thickness (CT) as a marker of retinopathy. We aimed to study choroidal and retinal changes associated with retinopathy in an animal model of spontaneous Type 2 diabetes, Goto-Kakizaki (GK) rats. Sclerochoroidal whole mounts and cryosections were prepared from 52-week-old GK and age-matched control Wistar Han rats. CT was measured by optical coherence tomography. Microglia reactivity, pericyte and endothelial cells distribution, and immunoreactivity of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) were evaluated by immunofluorescence. Choroidal vessels were visualized by direct perfusion with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil). Choroidal vascular density was evaluated by fluorescence microscopy. GK rats had increased CT (58.40 ± 1.15 μm versus 50.90 ± 1.58 μm, p < 0.001), reduced vascular density of the choriocapillaris (CC) (p = 0.045), increased Iba1+ cells density in the outer retina (p = 0.003) and increased VEGFR2 immunoreactivity in most retinal layers (p = 0.021 to 0.037). Choroidal microglial cells and pericytes showed polarity in their distribution, sparing the innermost choroid. This cell-free gap in the inner choroid was more pronounced in GK rats. In summary, GK rats have increased CT with decreased vascular density in the innermost choroid, increased VEGFR2 immunoreactivity in the retina and increased Iba1+ cells density in the outer retina.
publishDate 2020
dc.date.none.fl_str_mv 2020-12
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/10316/105816
http://hdl.handle.net/10316/105816
https://doi.org/10.1016/j.biopha.2020.110811
url http://hdl.handle.net/10316/105816
https://doi.org/10.1016/j.biopha.2020.110811
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 07533322
33069967
1950-6007
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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
repository.mail.fl_str_mv
_version_ 1799134112775143424