Transient Receptor Potential Vanilloid-1 Channels Facilitate Axonal Degeneration of Corneal Sensory Nerves in Dry Eye

Autores
Pizzano, Manuela; Vereertbrugghen, Alexia; Cernutto, Agostina; Sabbione, Florencia; Keitelman, Irene Angélica; Shiromizu, Carolina Maiumi; Vera Aguilar, Douglas; Fuentes, Federico; Giordano, Mirta Nilda; Trevani, Analía Silvina; Galletti, Jeremías Gastón
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Corneal nerve impairment contributes significantly to dry eye disease (DED) symptoms and is thought to be secondary to corneal epithelial damage. Transient receptor potential vanilloid-1 (TRPV1) channels abound in corneal nerve fibers and respond to inflammation-derived ligands, which increase in DED. TRPV1 overactivation promotes axonal degeneration in vitro, but whether it participates in DED-associated corneal nerve dysfunction is unknown. To explore this, DED was surgically induced in wild-type and TRPV1-knockout mice, which developed comparable corneal epithelial damage and reduced tear secretion. However, corneal mechanosensitivity decreased progressively only in wild-type DED mice. Sensitivity to capsaicin (TRPV1 agonist) increased in wild-type DED mice, and consistently, only this strain displayed DED-induced pain signs. Wild-type DED mice exhibited nerve degeneration throughout the corneal epithelium, whereas TRPV1-knockout DED mice only developed a reduction in the most superficial nerve endings that failed to propagate to the deeper subbasal corneal nerves. Pharmacologic TRPV1 blockade reproduced these findings in wild-type DED mice, whereas CD4+ T cells from both strains were equally pathogenic when transferred, ruling out a T-cell-mediated effect of TRPV1 deficiency. The data show that ocular desiccation triggers superficial corneal nerve damage in DED, but proximal propagation of axonal degeneration requires TRPV1 expression. Local inflammation sensitizes TRPV1 channels, which increases ocular pain. Thus, ocular TRPV1 overactivation drives DED-associated corneal nerve impairment.
Fil: Pizzano, Manuela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Vereertbrugghen, Alexia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Cernutto, Agostina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Sabbione, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Keitelman, Irene Angélica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Shiromizu, Carolina Maiumi. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Vera Aguilar, Douglas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Fuentes, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Giordano, Mirta Nilda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Trevani, Analía Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Galletti, Jeremías Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Materia
DRY EYE
TRPV1
CORNEAL NERVES
NEURODEGENERATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/267315
Acceder
id CONICETDig_559381c23ee0c1c4a19f4589312b94d5
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Transient Receptor Potential Vanilloid-1 Channels Facilitate Axonal Degeneration of Corneal Sensory Nerves in Dry EyePizzano, ManuelaVereertbrugghen, AlexiaCernutto, AgostinaSabbione, FlorenciaKeitelman, Irene AngélicaShiromizu, Carolina MaiumiVera Aguilar, DouglasFuentes, FedericoGiordano, Mirta NildaTrevani, Analía SilvinaGalletti, Jeremías GastónDRY EYETRPV1CORNEAL NERVESNEURODEGENERATIONhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Corneal nerve impairment contributes significantly to dry eye disease (DED) symptoms and is thought to be secondary to corneal epithelial damage. Transient receptor potential vanilloid-1 (TRPV1) channels abound in corneal nerve fibers and respond to inflammation-derived ligands, which increase in DED. TRPV1 overactivation promotes axonal degeneration in vitro, but whether it participates in DED-associated corneal nerve dysfunction is unknown. To explore this, DED was surgically induced in wild-type and TRPV1-knockout mice, which developed comparable corneal epithelial damage and reduced tear secretion. However, corneal mechanosensitivity decreased progressively only in wild-type DED mice. Sensitivity to capsaicin (TRPV1 agonist) increased in wild-type DED mice, and consistently, only this strain displayed DED-induced pain signs. Wild-type DED mice exhibited nerve degeneration throughout the corneal epithelium, whereas TRPV1-knockout DED mice only developed a reduction in the most superficial nerve endings that failed to propagate to the deeper subbasal corneal nerves. Pharmacologic TRPV1 blockade reproduced these findings in wild-type DED mice, whereas CD4+ T cells from both strains were equally pathogenic when transferred, ruling out a T-cell-mediated effect of TRPV1 deficiency. The data show that ocular desiccation triggers superficial corneal nerve damage in DED, but proximal propagation of axonal degeneration requires TRPV1 expression. Local inflammation sensitizes TRPV1 channels, which increases ocular pain. Thus, ocular TRPV1 overactivation drives DED-associated corneal nerve impairment.Fil: Pizzano, Manuela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Vereertbrugghen, Alexia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Cernutto, Agostina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Sabbione, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Keitelman, Irene Angélica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Shiromizu, Carolina Maiumi. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Vera Aguilar, Douglas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Fuentes, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Giordano, Mirta Nilda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Trevani, Analía Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Galletti, Jeremías Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaAmerican Society of Investigative Pathology2024-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/267315Pizzano, Manuela; Vereertbrugghen, Alexia; Cernutto, Agostina; Sabbione, Florencia; Keitelman, Irene Angélica; et al.; Transient Receptor Potential Vanilloid-1 Channels Facilitate Axonal Degeneration of Corneal Sensory Nerves in Dry Eye; American Society of Investigative Pathology; American Journal Of Pathology; 194; 5; 2-2024; 810-8270002-9440CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0002944024000476info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ajpath.2024.01.015info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:10:02Zoai:ri.conicet.gov.ar:11336/267315instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:10:03.077CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Transient Receptor Potential Vanilloid-1 Channels Facilitate Axonal Degeneration of Corneal Sensory Nerves in Dry Eye
title Transient Receptor Potential Vanilloid-1 Channels Facilitate Axonal Degeneration of Corneal Sensory Nerves in Dry Eye
spellingShingle Transient Receptor Potential Vanilloid-1 Channels Facilitate Axonal Degeneration of Corneal Sensory Nerves in Dry Eye
Pizzano, Manuela
DRY EYE
TRPV1
CORNEAL NERVES
NEURODEGENERATION
title_short Transient Receptor Potential Vanilloid-1 Channels Facilitate Axonal Degeneration of Corneal Sensory Nerves in Dry Eye
title_full Transient Receptor Potential Vanilloid-1 Channels Facilitate Axonal Degeneration of Corneal Sensory Nerves in Dry Eye
title_fullStr Transient Receptor Potential Vanilloid-1 Channels Facilitate Axonal Degeneration of Corneal Sensory Nerves in Dry Eye
title_full_unstemmed Transient Receptor Potential Vanilloid-1 Channels Facilitate Axonal Degeneration of Corneal Sensory Nerves in Dry Eye
title_sort Transient Receptor Potential Vanilloid-1 Channels Facilitate Axonal Degeneration of Corneal Sensory Nerves in Dry Eye
dc.creator.none.fl_str_mv Pizzano, Manuela
Vereertbrugghen, Alexia
Cernutto, Agostina
Sabbione, Florencia
Keitelman, Irene Angélica
Shiromizu, Carolina Maiumi
Vera Aguilar, Douglas
Fuentes, Federico
Giordano, Mirta Nilda
Trevani, Analía Silvina
Galletti, Jeremías Gastón
author Pizzano, Manuela
author_facet Pizzano, Manuela
Vereertbrugghen, Alexia
Cernutto, Agostina
Sabbione, Florencia
Keitelman, Irene Angélica
Shiromizu, Carolina Maiumi
Vera Aguilar, Douglas
Fuentes, Federico
Giordano, Mirta Nilda
Trevani, Analía Silvina
Galletti, Jeremías Gastón
author_role author
author2 Vereertbrugghen, Alexia
Cernutto, Agostina
Sabbione, Florencia
Keitelman, Irene Angélica
Shiromizu, Carolina Maiumi
Vera Aguilar, Douglas
Fuentes, Federico
Giordano, Mirta Nilda
Trevani, Analía Silvina
Galletti, Jeremías Gastón
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DRY EYE
TRPV1
CORNEAL NERVES
NEURODEGENERATION
topic DRY EYE
TRPV1
CORNEAL NERVES
NEURODEGENERATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Corneal nerve impairment contributes significantly to dry eye disease (DED) symptoms and is thought to be secondary to corneal epithelial damage. Transient receptor potential vanilloid-1 (TRPV1) channels abound in corneal nerve fibers and respond to inflammation-derived ligands, which increase in DED. TRPV1 overactivation promotes axonal degeneration in vitro, but whether it participates in DED-associated corneal nerve dysfunction is unknown. To explore this, DED was surgically induced in wild-type and TRPV1-knockout mice, which developed comparable corneal epithelial damage and reduced tear secretion. However, corneal mechanosensitivity decreased progressively only in wild-type DED mice. Sensitivity to capsaicin (TRPV1 agonist) increased in wild-type DED mice, and consistently, only this strain displayed DED-induced pain signs. Wild-type DED mice exhibited nerve degeneration throughout the corneal epithelium, whereas TRPV1-knockout DED mice only developed a reduction in the most superficial nerve endings that failed to propagate to the deeper subbasal corneal nerves. Pharmacologic TRPV1 blockade reproduced these findings in wild-type DED mice, whereas CD4+ T cells from both strains were equally pathogenic when transferred, ruling out a T-cell-mediated effect of TRPV1 deficiency. The data show that ocular desiccation triggers superficial corneal nerve damage in DED, but proximal propagation of axonal degeneration requires TRPV1 expression. Local inflammation sensitizes TRPV1 channels, which increases ocular pain. Thus, ocular TRPV1 overactivation drives DED-associated corneal nerve impairment.
Fil: Pizzano, Manuela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Vereertbrugghen, Alexia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Cernutto, Agostina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Sabbione, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Keitelman, Irene Angélica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Shiromizu, Carolina Maiumi. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Vera Aguilar, Douglas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Fuentes, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Giordano, Mirta Nilda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Trevani, Analía Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Galletti, Jeremías Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
description Corneal nerve impairment contributes significantly to dry eye disease (DED) symptoms and is thought to be secondary to corneal epithelial damage. Transient receptor potential vanilloid-1 (TRPV1) channels abound in corneal nerve fibers and respond to inflammation-derived ligands, which increase in DED. TRPV1 overactivation promotes axonal degeneration in vitro, but whether it participates in DED-associated corneal nerve dysfunction is unknown. To explore this, DED was surgically induced in wild-type and TRPV1-knockout mice, which developed comparable corneal epithelial damage and reduced tear secretion. However, corneal mechanosensitivity decreased progressively only in wild-type DED mice. Sensitivity to capsaicin (TRPV1 agonist) increased in wild-type DED mice, and consistently, only this strain displayed DED-induced pain signs. Wild-type DED mice exhibited nerve degeneration throughout the corneal epithelium, whereas TRPV1-knockout DED mice only developed a reduction in the most superficial nerve endings that failed to propagate to the deeper subbasal corneal nerves. Pharmacologic TRPV1 blockade reproduced these findings in wild-type DED mice, whereas CD4+ T cells from both strains were equally pathogenic when transferred, ruling out a T-cell-mediated effect of TRPV1 deficiency. The data show that ocular desiccation triggers superficial corneal nerve damage in DED, but proximal propagation of axonal degeneration requires TRPV1 expression. Local inflammation sensitizes TRPV1 channels, which increases ocular pain. Thus, ocular TRPV1 overactivation drives DED-associated corneal nerve impairment.
publishDate 2024
dc.date.none.fl_str_mv 2024-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
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info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/267315
Pizzano, Manuela; Vereertbrugghen, Alexia; Cernutto, Agostina; Sabbione, Florencia; Keitelman, Irene Angélica; et al.; Transient Receptor Potential Vanilloid-1 Channels Facilitate Axonal Degeneration of Corneal Sensory Nerves in Dry Eye; American Society of Investigative Pathology; American Journal Of Pathology; 194; 5; 2-2024; 810-827
0002-9440
CONICET Digital
CONICET
url http://hdl.handle.net/11336/267315
identifier_str_mv Pizzano, Manuela; Vereertbrugghen, Alexia; Cernutto, Agostina; Sabbione, Florencia; Keitelman, Irene Angélica; et al.; Transient Receptor Potential Vanilloid-1 Channels Facilitate Axonal Degeneration of Corneal Sensory Nerves in Dry Eye; American Society of Investigative Pathology; American Journal Of Pathology; 194; 5; 2-2024; 810-827
0002-9440
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ajpath.2024.01.015
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https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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dc.publisher.none.fl_str_mv American Society of Investigative Pathology
publisher.none.fl_str_mv American Society of Investigative Pathology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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reponame_str CONICET Digital (CONICET)
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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