VEGF in Tears as a Biomarker for Exudative Age-Related Macular Degeneration: Molecular Dynamics in a Mouse Model and Human Samples

Moshtaghion, Seyed Mohamadmehdi; Locri, Filippo; Plaza Reyes, Álvaro; Plastino, Flavia; Kvanta, Anders; Morillo-Sánchez, María José; Rodríguez de la Rúa Franch, Enrique; Gutiérrez-Sánchez, Estanislao; Montero-Sánchez, Adoración; Lucena-Padros, Helena; André, Helder; Díaz Corrales, Francisco J.

VEGF in Tears as a Biomarker for Exudative Age-Related Macular Degeneration: Molecular Dynamics in a Mouse Model and Human Samples

Vascular endothelial growth factor (VEGF) is a key mediator of exudative age-related macular degeneration (eAMD), yet non-invasive biomarkers for disease monitoring remain limited. This study evaluates VEGF levels in human tear fluid as a potential biomarker for eAMD and investigates the molecular d...

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Autores:	Moshtaghion, Seyed Mohamadmehdi, Locri, Filippo, Plaza Reyes, Álvaro, Plastino, Flavia, Kvanta, Anders, Morillo-Sánchez, María José, Rodríguez de la Rúa Franch, Enrique, Gutiérrez-Sánchez, Estanislao, Montero-Sánchez, Adoración, Lucena-Padros, Helena, André, Helder, Díaz Corrales, Francisco J.
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2025
País:	España
Institución:	Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:	DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:	oai:digital.csic.es:10261/391056
Acceso en línea:	http://hdl.handle.net/10261/391056 https://api.elsevier.com/content/abstract/scopus_id/105003769217
Access Level:	acceso abierto
Palabra clave:	Age-related macular degeneration Biomarker Choroidal neovascularization Tear fluid Vascular endothelial growth factor

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spelling	VEGF in Tears as a Biomarker for Exudative Age-Related Macular Degeneration: Molecular Dynamics in a Mouse Model and Human SamplesMoshtaghion, Seyed MohamadmehdiLocri, FilippoPlaza Reyes, ÁlvaroPlastino, FlaviaKvanta, AndersMorillo-Sánchez, María JoséRodríguez de la Rúa Franch, EnriqueGutiérrez-Sánchez, EstanislaoMontero-Sánchez, AdoraciónLucena-Padros, HelenaAndré, HelderDíaz Corrales, Francisco J.Age-related macular degenerationBiomarkerChoroidal neovascularizationTear fluidVascular endothelial growth factorVascular endothelial growth factor (VEGF) is a key mediator of exudative age-related macular degeneration (eAMD), yet non-invasive biomarkers for disease monitoring remain limited. This study evaluates VEGF levels in human tear fluid as a potential biomarker for eAMD and investigates the molecular dynamics of VEGF in a laser-induced choroidal neovascularization (lCNV) mouse model. Tear VEGF levels were quantified using proximity qPCR immunoassays in eAMD patients (n = 29) and healthy controls (n = 21) and correlated with optical coherence tomography (OCT) findings. Molecular analyses, including immunohistochemistry, gene expression profiling, and phosphorylation assays, were conducted on choroid-retinal pigment epithelium (RPE) and lacrimal gland (LG) tissues from lCNV mice (n = 25). Tear VEGF levels were significantly elevated in eAMD patients, correlating with disease severity. Females exhibited higher VEGF levels, a pattern not replicated in the mouse model. In lCNV mice, VEGF overexpression originated from the choroid-RPE, driven by hypoxic and inflammatory signaling, with no significant LG contribution. Increased VEGF, IL-6, and vimentin expression, along with NF-κB and STAT3 activation, were observed. These findings suggest that tear VEGF is a promising non-invasive biomarker for eAMD, warranting further validation for clinical application in disease monitoring and treatment optimization.This study was funded by Instituto de Salud Carlos III (ISCIII) through the project “RED 2024/0007/0035” and co-funded by the European Union, ISCIII, and Instituto de Salud Carlos III and the Fondo Europeo de Desarrollo Regional (Grant Numbers: PI17/01026, P-FIS: 21/00087), as well as the Junta de Andalucía, Programa Nicolás Monardes (Grant Number: C2-0009-2020). The preclinical and ex vivo models were supported by grants from the Karolinska Institutet Foundations and Funds, The Swedish Eye Foundation, and the ARMEC Lindeberg Foundation.Peer reviewedMultidisciplinary Digital Publishing InstituteInstituto de Salud Carlos IIIEuropean CommissionJunta de AndalucíaKarolinska Institutet FoundationSwedish Eye FoundationLindeberg FoundationMoshtaghion, Seyed Mohamadmehdi [0000-0002-6039-4246]Locri, Filippo [0009-0000-3772-8730]Plaza Reyes, Álvaro [0000-0003-1167-6316]Kvanta, Anders [0000-0003-2194-7490]Gutiérrez-Sánchez, Estanislao [0000-0003-4851-680X]Lucena-Padros, Helena [0000-0001-7569-3663]André, Helder [0000-0002-2926-2376]Díaz Corrales, Francisco J. [0000-0002-5752-0205]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/391056https://api.elsevier.com/content/abstract/scopus_id/105003769217reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésThe underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/ijms26083855https://doi.org/10.3390/ijms26083855Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3910562026-05-22T06:33:51Z
dc.title.none.fl_str_mv	VEGF in Tears as a Biomarker for Exudative Age-Related Macular Degeneration: Molecular Dynamics in a Mouse Model and Human Samples
title	VEGF in Tears as a Biomarker for Exudative Age-Related Macular Degeneration: Molecular Dynamics in a Mouse Model and Human Samples
spellingShingle	VEGF in Tears as a Biomarker for Exudative Age-Related Macular Degeneration: Molecular Dynamics in a Mouse Model and Human Samples Moshtaghion, Seyed Mohamadmehdi Age-related macular degeneration Biomarker Choroidal neovascularization Tear fluid Vascular endothelial growth factor
title_short	VEGF in Tears as a Biomarker for Exudative Age-Related Macular Degeneration: Molecular Dynamics in a Mouse Model and Human Samples
title_full	VEGF in Tears as a Biomarker for Exudative Age-Related Macular Degeneration: Molecular Dynamics in a Mouse Model and Human Samples
title_fullStr	VEGF in Tears as a Biomarker for Exudative Age-Related Macular Degeneration: Molecular Dynamics in a Mouse Model and Human Samples
title_full_unstemmed	VEGF in Tears as a Biomarker for Exudative Age-Related Macular Degeneration: Molecular Dynamics in a Mouse Model and Human Samples
title_sort	VEGF in Tears as a Biomarker for Exudative Age-Related Macular Degeneration: Molecular Dynamics in a Mouse Model and Human Samples
dc.creator.none.fl_str_mv	Moshtaghion, Seyed Mohamadmehdi Locri, Filippo Plaza Reyes, Álvaro Plastino, Flavia Kvanta, Anders Morillo-Sánchez, María José Rodríguez de la Rúa Franch, Enrique Gutiérrez-Sánchez, Estanislao Montero-Sánchez, Adoración Lucena-Padros, Helena André, Helder Díaz Corrales, Francisco J.
author	Moshtaghion, Seyed Mohamadmehdi
author_facet	Moshtaghion, Seyed Mohamadmehdi Locri, Filippo Plaza Reyes, Álvaro Plastino, Flavia Kvanta, Anders Morillo-Sánchez, María José Rodríguez de la Rúa Franch, Enrique Gutiérrez-Sánchez, Estanislao Montero-Sánchez, Adoración Lucena-Padros, Helena André, Helder Díaz Corrales, Francisco J.
author_role	author
author2	Locri, Filippo Plaza Reyes, Álvaro Plastino, Flavia Kvanta, Anders Morillo-Sánchez, María José Rodríguez de la Rúa Franch, Enrique Gutiérrez-Sánchez, Estanislao Montero-Sánchez, Adoración Lucena-Padros, Helena André, Helder Díaz Corrales, Francisco J.
author2_role	author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Instituto de Salud Carlos III European Commission Junta de Andalucía Karolinska Institutet Foundation Swedish Eye Foundation Lindeberg Foundation Moshtaghion, Seyed Mohamadmehdi [0000-0002-6039-4246] Locri, Filippo [0009-0000-3772-8730] Plaza Reyes, Álvaro [0000-0003-1167-6316] Kvanta, Anders [0000-0003-2194-7490] Gutiérrez-Sánchez, Estanislao [0000-0003-4851-680X] Lucena-Padros, Helena [0000-0001-7569-3663] André, Helder [0000-0002-2926-2376] Díaz Corrales, Francisco J. [0000-0002-5752-0205] Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv	Age-related macular degeneration Biomarker Choroidal neovascularization Tear fluid Vascular endothelial growth factor
topic	Age-related macular degeneration Biomarker Choroidal neovascularization Tear fluid Vascular endothelial growth factor
description	Vascular endothelial growth factor (VEGF) is a key mediator of exudative age-related macular degeneration (eAMD), yet non-invasive biomarkers for disease monitoring remain limited. This study evaluates VEGF levels in human tear fluid as a potential biomarker for eAMD and investigates the molecular dynamics of VEGF in a laser-induced choroidal neovascularization (lCNV) mouse model. Tear VEGF levels were quantified using proximity qPCR immunoassays in eAMD patients (n = 29) and healthy controls (n = 21) and correlated with optical coherence tomography (OCT) findings. Molecular analyses, including immunohistochemistry, gene expression profiling, and phosphorylation assays, were conducted on choroid-retinal pigment epithelium (RPE) and lacrimal gland (LG) tissues from lCNV mice (n = 25). Tear VEGF levels were significantly elevated in eAMD patients, correlating with disease severity. Females exhibited higher VEGF levels, a pattern not replicated in the mouse model. In lCNV mice, VEGF overexpression originated from the choroid-RPE, driven by hypoxic and inflammatory signaling, with no significant LG contribution. Increased VEGF, IL-6, and vimentin expression, along with NF-κB and STAT3 activation, were observed. These findings suggest that tear VEGF is a promising non-invasive biomarker for eAMD, warranting further validation for clinical application in disease monitoring and treatment optimization.
publishDate	2025
dc.date.none.fl_str_mv	2025 2025 2025
dc.type.none.fl_str_mv	info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	http://hdl.handle.net/10261/391056 https://api.elsevier.com/content/abstract/scopus_id/105003769217
url	http://hdl.handle.net/10261/391056 https://api.elsevier.com/content/abstract/scopus_id/105003769217
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/ijms26083855 https://doi.org/10.3390/ijms26083855 Sí
dc.rights.none.fl_str_mv	info:eu-repo/semantics/openAccess
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv	Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv	reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str	Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str	DIGITAL.CSIC. Repositorio Institucional del CSIC
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VEGF in Tears as a Biomarker for Exudative Age-Related Macular Degeneration: Molecular Dynamics in a Mouse Model and Human Samples

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