Effects of Cathepsin S Inhibition in the Age-Related Dry Eye Phenotype

Autores
Galletti, Jeremías Gastón; Scholand, Kaitlin K.; Trujillo Vargas, Claudia M.; Haap, Wolfgang; Santos Ferreira, Tiago; Ulmer, Christoph; Yu, Zhiyuan; de Paiva, Cintia S.
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
PURPOSE. Aged C57BL/6J (B6) mice have increased levels of cathepsin S, and aged cathepsin S (Ctss−/−) knockout mice are resistant to age-related dry eye. This study investigated the effects of cathepsin S inhibition on age-related dry eye disease. METHODS. Female B6 mice aged 15.5 to 17 months were randomized to receive a medicated diet formulated by mixing the RO5461111 cathepsin S inhibitor or a standard diet for at least 12 weeks. Cornea mechanosensitivity was measured with a Cochet–Bonnet esthesiometer. Ocular draining lymph nodes and lacrimal glands (LGs) were excised and prepared for histology or assayed by flow cytometry to quantify infiltrating immune cells. The inflammatory foci (>50 cells) were counted under a 10× microscope lens and quantified using the focus score. Goblet cell density was investigated in periodic acid–Schiff stained sections. Ctss−/− mice were compared to age-matched wild-type mice. RESULTS. Aged mice subjected to cathepsin S inhibition or Ctss−/− mice showed improved conjunctival goblet cell density and cornea mechanosensitivity. There was no change in total LG focus score in the diet or Ctss−/− mice, but there was a lower frequency of CD4+IFN-γ+ cell infiltration in the LGs. Furthermore, aged Ctss−/− LGs had an increase in T central memory, higher numbers of CD19+B220−, and fewer CD19+B220+ cells than wild-type LGs. CONCLUSIONS. Our results indicate that therapies aimed at decreasing cathepsin S can ameliorate age-related dry eye disease with a highly beneficial impact on the ocular surface. Further studies are needed to investigate the role of cathepsin S during aging.
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
Fil: Scholand, Kaitlin K.. Rice University; Estados Unidos
Fil: Trujillo Vargas, Claudia M.. Universidad de Antioquia; Colombia
Fil: Haap, Wolfgang. No especifíca;
Fil: Santos Ferreira, Tiago. No especifíca;
Fil: Ulmer, Christoph. No especifíca;
Fil: Yu, Zhiyuan. Baylor College of Medicine; Estados Unidos
Fil: de Paiva, Cintia S.. Baylor College of Medicine; Estados Unidos
Materia
AGING
DRY EYE
LACRIMAL GLAND
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/227670
Acceder
id CONICETDig_d58b5b5ef612679a8f395b263b619cf8
oai_identifier_str oai:ri.conicet.gov.ar:11336/227670
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Effects of Cathepsin S Inhibition in the Age-Related Dry Eye PhenotypeGalletti, Jeremías GastónScholand, Kaitlin K.Trujillo Vargas, Claudia M.Haap, WolfgangSantos Ferreira, TiagoUlmer, ChristophYu, Zhiyuande Paiva, Cintia S.AGINGDRY EYELACRIMAL GLANDhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3PURPOSE. Aged C57BL/6J (B6) mice have increased levels of cathepsin S, and aged cathepsin S (Ctss−/−) knockout mice are resistant to age-related dry eye. This study investigated the effects of cathepsin S inhibition on age-related dry eye disease. METHODS. Female B6 mice aged 15.5 to 17 months were randomized to receive a medicated diet formulated by mixing the RO5461111 cathepsin S inhibitor or a standard diet for at least 12 weeks. Cornea mechanosensitivity was measured with a Cochet–Bonnet esthesiometer. Ocular draining lymph nodes and lacrimal glands (LGs) were excised and prepared for histology or assayed by flow cytometry to quantify infiltrating immune cells. The inflammatory foci (>50 cells) were counted under a 10× microscope lens and quantified using the focus score. Goblet cell density was investigated in periodic acid–Schiff stained sections. Ctss−/− mice were compared to age-matched wild-type mice. RESULTS. Aged mice subjected to cathepsin S inhibition or Ctss−/− mice showed improved conjunctival goblet cell density and cornea mechanosensitivity. There was no change in total LG focus score in the diet or Ctss−/− mice, but there was a lower frequency of CD4+IFN-γ+ cell infiltration in the LGs. Furthermore, aged Ctss−/− LGs had an increase in T central memory, higher numbers of CD19+B220−, and fewer CD19+B220+ cells than wild-type LGs. CONCLUSIONS. Our results indicate that therapies aimed at decreasing cathepsin S can ameliorate age-related dry eye disease with a highly beneficial impact on the ocular surface. Further studies are needed to investigate the role of cathepsin S during aging.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; ArgentinaFil: Scholand, Kaitlin K.. Rice University; Estados UnidosFil: Trujillo Vargas, Claudia M.. Universidad de Antioquia; ColombiaFil: Haap, Wolfgang. No especifíca;Fil: Santos Ferreira, Tiago. No especifíca;Fil: Ulmer, Christoph. No especifíca;Fil: Yu, Zhiyuan. Baylor College of Medicine; Estados UnidosFil: de Paiva, Cintia S.. Baylor College of Medicine; Estados UnidosAssociation for Research in Vision and Ophthalmology2023-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/227670Galletti, Jeremías Gastón; Scholand, Kaitlin K.; Trujillo Vargas, Claudia M.; Haap, Wolfgang; Santos Ferreira, Tiago; et al.; Effects of Cathepsin S Inhibition in the Age-Related Dry Eye Phenotype; Association for Research in Vision and Ophthalmology; Investigative Ophthalmology & Visual Science; 64; 11; 8-2023; 1-121552-5783CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://iovs.arvojournals.org/article.aspx?articleid=2791373info:eu-repo/semantics/altIdentifier/doi/10.1167/iovs.64.11.7info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:09:57Zoai:ri.conicet.gov.ar:11336/227670instacron: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:34982025-09-29 10:09:57.291CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Effects of Cathepsin S Inhibition in the Age-Related Dry Eye Phenotype
title Effects of Cathepsin S Inhibition in the Age-Related Dry Eye Phenotype
spellingShingle Effects of Cathepsin S Inhibition in the Age-Related Dry Eye Phenotype
Galletti, Jeremías Gastón
AGING
DRY EYE
LACRIMAL GLAND
title_short Effects of Cathepsin S Inhibition in the Age-Related Dry Eye Phenotype
title_full Effects of Cathepsin S Inhibition in the Age-Related Dry Eye Phenotype
title_fullStr Effects of Cathepsin S Inhibition in the Age-Related Dry Eye Phenotype
title_full_unstemmed Effects of Cathepsin S Inhibition in the Age-Related Dry Eye Phenotype
title_sort Effects of Cathepsin S Inhibition in the Age-Related Dry Eye Phenotype
dc.creator.none.fl_str_mv Galletti, Jeremías Gastón
Scholand, Kaitlin K.
Trujillo Vargas, Claudia M.
Haap, Wolfgang
Santos Ferreira, Tiago
Ulmer, Christoph
Yu, Zhiyuan
de Paiva, Cintia S.
author Galletti, Jeremías Gastón
author_facet Galletti, Jeremías Gastón
Scholand, Kaitlin K.
Trujillo Vargas, Claudia M.
Haap, Wolfgang
Santos Ferreira, Tiago
Ulmer, Christoph
Yu, Zhiyuan
de Paiva, Cintia S.
author_role author
author2 Scholand, Kaitlin K.
Trujillo Vargas, Claudia M.
Haap, Wolfgang
Santos Ferreira, Tiago
Ulmer, Christoph
Yu, Zhiyuan
de Paiva, Cintia S.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AGING
DRY EYE
LACRIMAL GLAND
topic AGING
DRY EYE
LACRIMAL GLAND
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv PURPOSE. Aged C57BL/6J (B6) mice have increased levels of cathepsin S, and aged cathepsin S (Ctss−/−) knockout mice are resistant to age-related dry eye. This study investigated the effects of cathepsin S inhibition on age-related dry eye disease. METHODS. Female B6 mice aged 15.5 to 17 months were randomized to receive a medicated diet formulated by mixing the RO5461111 cathepsin S inhibitor or a standard diet for at least 12 weeks. Cornea mechanosensitivity was measured with a Cochet–Bonnet esthesiometer. Ocular draining lymph nodes and lacrimal glands (LGs) were excised and prepared for histology or assayed by flow cytometry to quantify infiltrating immune cells. The inflammatory foci (>50 cells) were counted under a 10× microscope lens and quantified using the focus score. Goblet cell density was investigated in periodic acid–Schiff stained sections. Ctss−/− mice were compared to age-matched wild-type mice. RESULTS. Aged mice subjected to cathepsin S inhibition or Ctss−/− mice showed improved conjunctival goblet cell density and cornea mechanosensitivity. There was no change in total LG focus score in the diet or Ctss−/− mice, but there was a lower frequency of CD4+IFN-γ+ cell infiltration in the LGs. Furthermore, aged Ctss−/− LGs had an increase in T central memory, higher numbers of CD19+B220−, and fewer CD19+B220+ cells than wild-type LGs. CONCLUSIONS. Our results indicate that therapies aimed at decreasing cathepsin S can ameliorate age-related dry eye disease with a highly beneficial impact on the ocular surface. Further studies are needed to investigate the role of cathepsin S during aging.
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
Fil: Scholand, Kaitlin K.. Rice University; Estados Unidos
Fil: Trujillo Vargas, Claudia M.. Universidad de Antioquia; Colombia
Fil: Haap, Wolfgang. No especifíca;
Fil: Santos Ferreira, Tiago. No especifíca;
Fil: Ulmer, Christoph. No especifíca;
Fil: Yu, Zhiyuan. Baylor College of Medicine; Estados Unidos
Fil: de Paiva, Cintia S.. Baylor College of Medicine; Estados Unidos
description PURPOSE. Aged C57BL/6J (B6) mice have increased levels of cathepsin S, and aged cathepsin S (Ctss−/−) knockout mice are resistant to age-related dry eye. This study investigated the effects of cathepsin S inhibition on age-related dry eye disease. METHODS. Female B6 mice aged 15.5 to 17 months were randomized to receive a medicated diet formulated by mixing the RO5461111 cathepsin S inhibitor or a standard diet for at least 12 weeks. Cornea mechanosensitivity was measured with a Cochet–Bonnet esthesiometer. Ocular draining lymph nodes and lacrimal glands (LGs) were excised and prepared for histology or assayed by flow cytometry to quantify infiltrating immune cells. The inflammatory foci (>50 cells) were counted under a 10× microscope lens and quantified using the focus score. Goblet cell density was investigated in periodic acid–Schiff stained sections. Ctss−/− mice were compared to age-matched wild-type mice. RESULTS. Aged mice subjected to cathepsin S inhibition or Ctss−/− mice showed improved conjunctival goblet cell density and cornea mechanosensitivity. There was no change in total LG focus score in the diet or Ctss−/− mice, but there was a lower frequency of CD4+IFN-γ+ cell infiltration in the LGs. Furthermore, aged Ctss−/− LGs had an increase in T central memory, higher numbers of CD19+B220−, and fewer CD19+B220+ cells than wild-type LGs. CONCLUSIONS. Our results indicate that therapies aimed at decreasing cathepsin S can ameliorate age-related dry eye disease with a highly beneficial impact on the ocular surface. Further studies are needed to investigate the role of cathepsin S during aging.
publishDate 2023
dc.date.none.fl_str_mv 2023-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/227670
Galletti, Jeremías Gastón; Scholand, Kaitlin K.; Trujillo Vargas, Claudia M.; Haap, Wolfgang; Santos Ferreira, Tiago; et al.; Effects of Cathepsin S Inhibition in the Age-Related Dry Eye Phenotype; Association for Research in Vision and Ophthalmology; Investigative Ophthalmology & Visual Science; 64; 11; 8-2023; 1-12
1552-5783
CONICET Digital
CONICET
url http://hdl.handle.net/11336/227670
identifier_str_mv Galletti, Jeremías Gastón; Scholand, Kaitlin K.; Trujillo Vargas, Claudia M.; Haap, Wolfgang; Santos Ferreira, Tiago; et al.; Effects of Cathepsin S Inhibition in the Age-Related Dry Eye Phenotype; Association for Research in Vision and Ophthalmology; Investigative Ophthalmology & Visual Science; 64; 11; 8-2023; 1-12
1552-5783
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://iovs.arvojournals.org/article.aspx?articleid=2791373
info:eu-repo/semantics/altIdentifier/doi/10.1167/iovs.64.11.7
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Association for Research in Vision and Ophthalmology
publisher.none.fl_str_mv Association for Research in Vision and Ophthalmology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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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score 13.070432

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