Formation of lipofuscin-like autofluorescent granules in the retinal pigment epithelium requires lysosome dysfunction

Detalhes bibliográficos
Autor(a) principal: Escrevente, Cristina
Data de Publicação: 2021
Outros Autores: Falcão, Ana S., Hall, Michael J., Lopes-Da-Silva, Mafalda, Antas, Pedro, Mesquita, Miguel M., Ferreira, Inês S., Helena Cardoso, M., Oliveira, Daniela, Fradinho, Ana C., Ciossek, Thomas, Nicklin, Paul, Futter, Clare E., Tenreiro, Sandra, Seabra, Miguel C.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/126474
Resumo: Funding Information: Supported by Funda??o para a Ciência e Tecnologia (FCT) ? Portugal co-funded by FEDER under the PT2020 Partnership Agreement (to MCS, including project PTDC/MED-PAT/30385/2017, iNOVA4Health-UIDB/04462/2020, research infrastructure PPBI-POCI-01-0145-FEDER-022122, M-ERA.NET 2/0005/2016), Boehringer Ingelheim (to MCS), Fight for Sight UK (to MCS), Wellcome Trust grant number 212216/Z/18/Z/ (to CEF). MJH was funded by Moor-fields Eye Charity with the Bill Brown 1989 Charitable Trust PhD studentship 538158, MLS was funded by FCT-CEECIND/01536/2018, ACF was funded by FCT PhD studentship (PD/BD/135503/2018). This work was developed with the support from the research infrastructure PPBI-POCI-01-0145-FEDER-022122, co-financed by FCT (Portugal) and Lisboa2020, under the PORTUGAL2020 agreement (European Regional Development Fund) and this article is supported by the LYSOCIL project funded by the European Union?s Horizon 2020 programme under grant agreement No. 811087. Funding Information: Supported by Fundação para a Ciência e Tecnologia (FCT) – Portugal co-funded by FEDER under the PT2020 Partnership Agreement (to MCS, including project PTDC/MED-PAT/30385/2017, iNOVA4Health-UIDB/04462/2020, research infrastructure PPBI-POCI-01-0145-FEDER-022122, M-ERA.NET 2/0005/2016), Boehringer Ingelheim (to MCS), Fight for Sight UK (to MCS), Wellcome Trust grant number 212216/Z/18/Z/ (to CEF). MJH was funded by Moor-fields Eye Charity with the Bill Brown 1989 Charitable Trust PhD studentship 538158, MLS was funded by FCT-CEECIND/01536/2018, ACF was funded by FCT PhD studentship (PD/BD/135503/2018). This work was developed with the support from the research infrastructure PPBI-POCI-01-0145-FEDER-022122, co-financed by FCT (Portugal) and Lisboa2020, under the PORTUGAL2020 agreement (European Regional Development Fund) and this article is supported by the LYSOCIL project funded by the European Union’s Horizon 2020 programme under grant agreement No. 811087. Publisher Copyright: Copyright 2021 The Authors
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network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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spelling Formation of lipofuscin-like autofluorescent granules in the retinal pigment epithelium requires lysosome dysfunctionAutofluorescent granulesLipofuscinLysosome dysfunctionPhotoreceptor outer segmentsRetinal pigmented epitheliumOphthalmologySensory SystemsCellular and Molecular NeuroscienceFunding Information: Supported by Funda??o para a Ciência e Tecnologia (FCT) ? Portugal co-funded by FEDER under the PT2020 Partnership Agreement (to MCS, including project PTDC/MED-PAT/30385/2017, iNOVA4Health-UIDB/04462/2020, research infrastructure PPBI-POCI-01-0145-FEDER-022122, M-ERA.NET 2/0005/2016), Boehringer Ingelheim (to MCS), Fight for Sight UK (to MCS), Wellcome Trust grant number 212216/Z/18/Z/ (to CEF). MJH was funded by Moor-fields Eye Charity with the Bill Brown 1989 Charitable Trust PhD studentship 538158, MLS was funded by FCT-CEECIND/01536/2018, ACF was funded by FCT PhD studentship (PD/BD/135503/2018). This work was developed with the support from the research infrastructure PPBI-POCI-01-0145-FEDER-022122, co-financed by FCT (Portugal) and Lisboa2020, under the PORTUGAL2020 agreement (European Regional Development Fund) and this article is supported by the LYSOCIL project funded by the European Union?s Horizon 2020 programme under grant agreement No. 811087. Funding Information: Supported by Fundação para a Ciência e Tecnologia (FCT) – Portugal co-funded by FEDER under the PT2020 Partnership Agreement (to MCS, including project PTDC/MED-PAT/30385/2017, iNOVA4Health-UIDB/04462/2020, research infrastructure PPBI-POCI-01-0145-FEDER-022122, M-ERA.NET 2/0005/2016), Boehringer Ingelheim (to MCS), Fight for Sight UK (to MCS), Wellcome Trust grant number 212216/Z/18/Z/ (to CEF). MJH was funded by Moor-fields Eye Charity with the Bill Brown 1989 Charitable Trust PhD studentship 538158, MLS was funded by FCT-CEECIND/01536/2018, ACF was funded by FCT PhD studentship (PD/BD/135503/2018). This work was developed with the support from the research infrastructure PPBI-POCI-01-0145-FEDER-022122, co-financed by FCT (Portugal) and Lisboa2020, under the PORTUGAL2020 agreement (European Regional Development Fund) and this article is supported by the LYSOCIL project funded by the European Union’s Horizon 2020 programme under grant agreement No. 811087. Publisher Copyright: Copyright 2021 The AuthorsPURPOSE. We aim to characterize the pathways required for autofluorescent granule (AFG) formation by RPE cells using cultured monolayers. METHODS. We fed RPE monolayers in culture with a single pulse of photoreceptor outer segments (POS). After 24 hours the cells started accumulating AFGs that were comparable to lipofuscin in vivo. Using this model, we used a variety of light and electron microscopical techniques, flow cytometry and Western blot to analyze the formation of AFGs. We also generated a mutant RPE line lacking cathepsin D by gene editing. RESULTS. AFGs seem to derive from incompletely digested POS-containing phagosomes and after 3 days are surrounded by a single membrane positive for lysosome markers. We show by various methods that lysosome-phagosome fusion is required for AFG formation, and that impairment of lysosomal pH or catalytic activity, particularly cathepsin D activity, enhances AF accumulation. CONCLUSIONS. We conclude that lysosomal dysfunction results in incomplete POS degradation and enhanced AFG accumulation.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)iNOVA4Health - pólo NMSRUNEscrevente, CristinaFalcão, Ana S.Hall, Michael J.Lopes-Da-Silva, MafaldaAntas, PedroMesquita, Miguel M.Ferreira, Inês S.Helena Cardoso, M.Oliveira, DanielaFradinho, Ana C.Ciossek, ThomasNicklin, PaulFutter, Clare E.Tenreiro, SandraSeabra, Miguel C.2021-10-22T03:42:48Z2021-072021-07-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/126474eng0146-0404PURE: 33696510https://doi.org/10.1167/iovs.62.9.39info: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:RCAAP2024-03-11T05:06:53Zoai:run.unl.pt:10362/126474Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:45:53.409504Repositório 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 Formation of lipofuscin-like autofluorescent granules in the retinal pigment epithelium requires lysosome dysfunction
title Formation of lipofuscin-like autofluorescent granules in the retinal pigment epithelium requires lysosome dysfunction
spellingShingle Formation of lipofuscin-like autofluorescent granules in the retinal pigment epithelium requires lysosome dysfunction
Escrevente, Cristina
Autofluorescent granules
Lipofuscin
Lysosome dysfunction
Photoreceptor outer segments
Retinal pigmented epithelium
Ophthalmology
Sensory Systems
Cellular and Molecular Neuroscience
title_short Formation of lipofuscin-like autofluorescent granules in the retinal pigment epithelium requires lysosome dysfunction
title_full Formation of lipofuscin-like autofluorescent granules in the retinal pigment epithelium requires lysosome dysfunction
title_fullStr Formation of lipofuscin-like autofluorescent granules in the retinal pigment epithelium requires lysosome dysfunction
title_full_unstemmed Formation of lipofuscin-like autofluorescent granules in the retinal pigment epithelium requires lysosome dysfunction
title_sort Formation of lipofuscin-like autofluorescent granules in the retinal pigment epithelium requires lysosome dysfunction
author Escrevente, Cristina
author_facet Escrevente, Cristina
Falcão, Ana S.
Hall, Michael J.
Lopes-Da-Silva, Mafalda
Antas, Pedro
Mesquita, Miguel M.
Ferreira, Inês S.
Helena Cardoso, M.
Oliveira, Daniela
Fradinho, Ana C.
Ciossek, Thomas
Nicklin, Paul
Futter, Clare E.
Tenreiro, Sandra
Seabra, Miguel C.
author_role author
author2 Falcão, Ana S.
Hall, Michael J.
Lopes-Da-Silva, Mafalda
Antas, Pedro
Mesquita, Miguel M.
Ferreira, Inês S.
Helena Cardoso, M.
Oliveira, Daniela
Fradinho, Ana C.
Ciossek, Thomas
Nicklin, Paul
Futter, Clare E.
Tenreiro, Sandra
Seabra, Miguel C.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
Centro de Estudos de Doenças Crónicas (CEDOC)
iNOVA4Health - pólo NMS
RUN
dc.contributor.author.fl_str_mv Escrevente, Cristina
Falcão, Ana S.
Hall, Michael J.
Lopes-Da-Silva, Mafalda
Antas, Pedro
Mesquita, Miguel M.
Ferreira, Inês S.
Helena Cardoso, M.
Oliveira, Daniela
Fradinho, Ana C.
Ciossek, Thomas
Nicklin, Paul
Futter, Clare E.
Tenreiro, Sandra
Seabra, Miguel C.
dc.subject.por.fl_str_mv Autofluorescent granules
Lipofuscin
Lysosome dysfunction
Photoreceptor outer segments
Retinal pigmented epithelium
Ophthalmology
Sensory Systems
Cellular and Molecular Neuroscience
topic Autofluorescent granules
Lipofuscin
Lysosome dysfunction
Photoreceptor outer segments
Retinal pigmented epithelium
Ophthalmology
Sensory Systems
Cellular and Molecular Neuroscience
description Funding Information: Supported by Funda??o para a Ciência e Tecnologia (FCT) ? Portugal co-funded by FEDER under the PT2020 Partnership Agreement (to MCS, including project PTDC/MED-PAT/30385/2017, iNOVA4Health-UIDB/04462/2020, research infrastructure PPBI-POCI-01-0145-FEDER-022122, M-ERA.NET 2/0005/2016), Boehringer Ingelheim (to MCS), Fight for Sight UK (to MCS), Wellcome Trust grant number 212216/Z/18/Z/ (to CEF). MJH was funded by Moor-fields Eye Charity with the Bill Brown 1989 Charitable Trust PhD studentship 538158, MLS was funded by FCT-CEECIND/01536/2018, ACF was funded by FCT PhD studentship (PD/BD/135503/2018). This work was developed with the support from the research infrastructure PPBI-POCI-01-0145-FEDER-022122, co-financed by FCT (Portugal) and Lisboa2020, under the PORTUGAL2020 agreement (European Regional Development Fund) and this article is supported by the LYSOCIL project funded by the European Union?s Horizon 2020 programme under grant agreement No. 811087. Funding Information: Supported by Fundação para a Ciência e Tecnologia (FCT) – Portugal co-funded by FEDER under the PT2020 Partnership Agreement (to MCS, including project PTDC/MED-PAT/30385/2017, iNOVA4Health-UIDB/04462/2020, research infrastructure PPBI-POCI-01-0145-FEDER-022122, M-ERA.NET 2/0005/2016), Boehringer Ingelheim (to MCS), Fight for Sight UK (to MCS), Wellcome Trust grant number 212216/Z/18/Z/ (to CEF). MJH was funded by Moor-fields Eye Charity with the Bill Brown 1989 Charitable Trust PhD studentship 538158, MLS was funded by FCT-CEECIND/01536/2018, ACF was funded by FCT PhD studentship (PD/BD/135503/2018). This work was developed with the support from the research infrastructure PPBI-POCI-01-0145-FEDER-022122, co-financed by FCT (Portugal) and Lisboa2020, under the PORTUGAL2020 agreement (European Regional Development Fund) and this article is supported by the LYSOCIL project funded by the European Union’s Horizon 2020 programme under grant agreement No. 811087. Publisher Copyright: Copyright 2021 The Authors
publishDate 2021
dc.date.none.fl_str_mv 2021-10-22T03:42:48Z
2021-07
2021-07-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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url http://hdl.handle.net/10362/126474
dc.language.iso.fl_str_mv eng
language eng
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PURE: 33696510
https://doi.org/10.1167/iovs.62.9.39
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eu_rights_str_mv openAccess
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instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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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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