Unraveling the nexus of oxidative stress, ocular diseases, and small extracellular vesicles to identify novel glaucoma biomarkers through in-depth proteomics

Chronic ocular pathologies such as cataracts and glaucoma are emerging as an important problem for public health due to the changes in lifestyle and longevity. These age-related ocular diseases are largely mediated by oxidative stress. Small extracellular vesicles (sEVs) are involved in cell-to-cell...

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Autores: Rejas-González, Raquel, Montero-Calle, Ana, Pastora Salvador, Natalia, Crespo Carballés, María José, Ausín-González, Emma, Sánchez-Naves, Juan, Pardo Calderón, Sara, Barderas Manchado, Rodrigo, Guzmán Aránguez, Ana Isabel
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/109705
Acceso en línea:https://hdl.handle.net/20.500.14352/109705
Access Level:acceso abierto
Palabra clave:613/614
617.7-007.681-079
Aqueous humor
Cataracts
Glaucoma
Glaucoma diagnosis
Proteomics
Small extracellular vesicles
Bioquímica (Medicina)
Oftalmología
3201.09 Oftalmología
2302 Bioquímica
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oai_identifier_str oai:docta.ucm.es:20.500.14352/109705
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network_name_str España
repository_id_str
spelling Unraveling the nexus of oxidative stress, ocular diseases, and small extracellular vesicles to identify novel glaucoma biomarkers through in-depth proteomicsRejas-González, RaquelMontero-Calle, AnaPastora Salvador, NataliaCrespo Carballés, María JoséAusín-González, EmmaSánchez-Naves, JuanPardo Calderón, SaraBarderas Manchado, RodrigoGuzmán Aránguez, Ana Isabel613/614617.7-007.681-079Aqueous humorCataractsGlaucomaGlaucoma diagnosisProteomicsSmall extracellular vesiclesBioquímica (Medicina)Oftalmología3201.09 Oftalmología2302 BioquímicaChronic ocular pathologies such as cataracts and glaucoma are emerging as an important problem for public health due to the changes in lifestyle and longevity. These age-related ocular diseases are largely mediated by oxidative stress. Small extracellular vesicles (sEVs) are involved in cell-to-cell communication and transport. There is an increasing interest about the function of small extracellular vesicles (sEVs) in the eye. However, the proteome content and characterization of sEVs released by ocular cells under pathological conditions are not yet well known. Here, we aimed to analyze the protein profile of sEVs and the intracellular protein content from two ocular cell lines (lens epithelial cells and retinal ganglion cells) exposed to oxidative stress to identify altered proteins that could serve as potential diagnostic biomarkers. The protein content was analyzed by quantitative mass spectrometry-based proteomics. Validation was performed by WB and ELISA using cell extracts and aqueous humor from cataract and glaucoma patients. After data analysis, 176 and 7 dysregulated proteins with an expression ratio≥1.5 were identified in lens epithelial cells' protein extract and sEVs, respectively, upon oxidative stress induction. In retinal ganglion cells, oxidative stress induction resulted in the dysregulation of 1033 proteins in cell extracts and 9 proteins in sEVs. In addition, by WB and ELISA, the dysregulation of proteins was mostly confirmed in aqueous humor samples from cataract or glaucoma patients in comparison to ICL individuals, with RAD23B showing high glaucoma diagnostic ability. Importantly, this work expands the knowledge of the proteome characterization of cataracts and glaucoma and provides new potential diagnostic glaucoma biomarkers.ElsevierUniversidad Complutense de Madrid20242024-01-0120242024-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/109705reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1097052026-06-02T12:44:21Z
dc.title.none.fl_str_mv Unraveling the nexus of oxidative stress, ocular diseases, and small extracellular vesicles to identify novel glaucoma biomarkers through in-depth proteomics
title Unraveling the nexus of oxidative stress, ocular diseases, and small extracellular vesicles to identify novel glaucoma biomarkers through in-depth proteomics
spellingShingle Unraveling the nexus of oxidative stress, ocular diseases, and small extracellular vesicles to identify novel glaucoma biomarkers through in-depth proteomics
Rejas-González, Raquel
613/614
617.7-007.681-079
Aqueous humor
Cataracts
Glaucoma
Glaucoma diagnosis
Proteomics
Small extracellular vesicles
Bioquímica (Medicina)
Oftalmología
3201.09 Oftalmología
2302 Bioquímica
title_short Unraveling the nexus of oxidative stress, ocular diseases, and small extracellular vesicles to identify novel glaucoma biomarkers through in-depth proteomics
title_full Unraveling the nexus of oxidative stress, ocular diseases, and small extracellular vesicles to identify novel glaucoma biomarkers through in-depth proteomics
title_fullStr Unraveling the nexus of oxidative stress, ocular diseases, and small extracellular vesicles to identify novel glaucoma biomarkers through in-depth proteomics
title_full_unstemmed Unraveling the nexus of oxidative stress, ocular diseases, and small extracellular vesicles to identify novel glaucoma biomarkers through in-depth proteomics
title_sort Unraveling the nexus of oxidative stress, ocular diseases, and small extracellular vesicles to identify novel glaucoma biomarkers through in-depth proteomics
dc.creator.none.fl_str_mv Rejas-González, Raquel
Montero-Calle, Ana
Pastora Salvador, Natalia
Crespo Carballés, María José
Ausín-González, Emma
Sánchez-Naves, Juan
Pardo Calderón, Sara
Barderas Manchado, Rodrigo
Guzmán Aránguez, Ana Isabel
author Rejas-González, Raquel
author_facet Rejas-González, Raquel
Montero-Calle, Ana
Pastora Salvador, Natalia
Crespo Carballés, María José
Ausín-González, Emma
Sánchez-Naves, Juan
Pardo Calderón, Sara
Barderas Manchado, Rodrigo
Guzmán Aránguez, Ana Isabel
author_role author
author2 Montero-Calle, Ana
Pastora Salvador, Natalia
Crespo Carballés, María José
Ausín-González, Emma
Sánchez-Naves, Juan
Pardo Calderón, Sara
Barderas Manchado, Rodrigo
Guzmán Aránguez, Ana Isabel
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 613/614
617.7-007.681-079
Aqueous humor
Cataracts
Glaucoma
Glaucoma diagnosis
Proteomics
Small extracellular vesicles
Bioquímica (Medicina)
Oftalmología
3201.09 Oftalmología
2302 Bioquímica
topic 613/614
617.7-007.681-079
Aqueous humor
Cataracts
Glaucoma
Glaucoma diagnosis
Proteomics
Small extracellular vesicles
Bioquímica (Medicina)
Oftalmología
3201.09 Oftalmología
2302 Bioquímica
description Chronic ocular pathologies such as cataracts and glaucoma are emerging as an important problem for public health due to the changes in lifestyle and longevity. These age-related ocular diseases are largely mediated by oxidative stress. Small extracellular vesicles (sEVs) are involved in cell-to-cell communication and transport. There is an increasing interest about the function of small extracellular vesicles (sEVs) in the eye. However, the proteome content and characterization of sEVs released by ocular cells under pathological conditions are not yet well known. Here, we aimed to analyze the protein profile of sEVs and the intracellular protein content from two ocular cell lines (lens epithelial cells and retinal ganglion cells) exposed to oxidative stress to identify altered proteins that could serve as potential diagnostic biomarkers. The protein content was analyzed by quantitative mass spectrometry-based proteomics. Validation was performed by WB and ELISA using cell extracts and aqueous humor from cataract and glaucoma patients. After data analysis, 176 and 7 dysregulated proteins with an expression ratio≥1.5 were identified in lens epithelial cells' protein extract and sEVs, respectively, upon oxidative stress induction. In retinal ganglion cells, oxidative stress induction resulted in the dysregulation of 1033 proteins in cell extracts and 9 proteins in sEVs. In addition, by WB and ELISA, the dysregulation of proteins was mostly confirmed in aqueous humor samples from cataract or glaucoma patients in comparison to ICL individuals, with RAD23B showing high glaucoma diagnostic ability. Importantly, this work expands the knowledge of the proteome characterization of cataracts and glaucoma and provides new potential diagnostic glaucoma biomarkers.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-01-01
2024
2024-01-01
dc.type.none.fl_str_mv journal 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://hdl.handle.net/20.500.14352/109705
url https://hdl.handle.net/20.500.14352/109705
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
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/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
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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