Methylene Blue Reduces Electroretinogram Distortion and Ganglion Cell Death in a Rat Model of Glaucoma

Autores
Nakamura, Ronan; Ciranna, Nicolás S.; Fernández, Juan C.; Peláez, Rafael; Pérez Sala, Álvaro; Bobadilla, Miriam; López, Juan José; Loidl, Cesar Fabian; Martínez, Alfredo; Rey Funes, Manuel
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Glaucoma is the second leading cause of blindness worldwide and is, in most cases, a consequence of elevated intraocular pressure (IOP), ultimately resulting in the death of retinal ganglion cells (RGCs). Current treatments are mostly focused on normalizing IOP, but we propose the additional use of neuroprotective agents, including methylene blue (MB), to block the loss of RGCs. Wistar rats were subjected to episcleral vein cauterization (EVC) in the left eye while the right eye was sham-operated. One week later, they were divided into two groups, which were injected with either 2.0 mg/kg MB or phosphate-buffered saline (PBS), twice a day, for 7 days. Fifteen days after surgery, rats were tested with scotopic electroretinography (ERG) or pattern electroretinography (PERG). After sacrifice, the number of RGCs and the thickness of the inner retina (IR) were evaluated both in the peripheral and central areas of the retina. Scotopic ERG showed a marked reduction (p < 0.0001) on the a- and b-wave amplitude and oscillatory potential (OP) complexity of the eyes subjected to EVC. These parameters were significantly (p < 0.01) restored by the application of MB. PERG indicated that EVC was responsible for a very significant decrease in N2 amplitude (p < 0.0001) and prolongation of N2 implicit time (p < 0.0001). Treatment with MB significantly restored N2 amplitude (p < 0.0001). In parallel with the ERG results, morphological analysis showed a significant loss of RGCs (p < 0.0001) and IR thickness (p < 0.0001) in both the peripheral and central retinas subjected to EVC, which was significantly prevented (p < 0.0001) by MB treatment. We have shown that MB treatment can be effective in preventing physiological and morphological hallmarks of optic neuropathy in a model of ocular hypertension, which faithfully recapitulates human open-angle glaucoma. Due to its high safety profile, this drug could therefore represent a new pharmacologic strategy to prevent vision loss in glaucoma patients.
Fil: Nakamura, Ronan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Ciranna, Nicolás S.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Fernández, Juan C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Peláez, Rafael. No especifíca;
Fil: Pérez Sala, Álvaro. No especifíca;
Fil: Bobadilla, Miriam. No especifíca;
Fil: López, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Loidl, Cesar Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Martínez, Alfredo. No especifíca;
Fil: Rey Funes, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Materia
DEGENERATION
GANGLION CELL
GLAUCOMA
METHYLENE BLUE
RETINA
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:11336/267438
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/267438
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Methylene Blue Reduces Electroretinogram Distortion and Ganglion Cell Death in a Rat Model of GlaucomaNakamura, RonanCiranna, Nicolás S.Fernández, Juan C.Peláez, RafaelPérez Sala, ÁlvaroBobadilla, MiriamLópez, Juan JoséLoidl, Cesar FabianMartínez, AlfredoRey Funes, ManuelDEGENERATIONGANGLION CELLGLAUCOMAMETHYLENE BLUERETINAhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Glaucoma is the second leading cause of blindness worldwide and is, in most cases, a consequence of elevated intraocular pressure (IOP), ultimately resulting in the death of retinal ganglion cells (RGCs). Current treatments are mostly focused on normalizing IOP, but we propose the additional use of neuroprotective agents, including methylene blue (MB), to block the loss of RGCs. Wistar rats were subjected to episcleral vein cauterization (EVC) in the left eye while the right eye was sham-operated. One week later, they were divided into two groups, which were injected with either 2.0 mg/kg MB or phosphate-buffered saline (PBS), twice a day, for 7 days. Fifteen days after surgery, rats were tested with scotopic electroretinography (ERG) or pattern electroretinography (PERG). After sacrifice, the number of RGCs and the thickness of the inner retina (IR) were evaluated both in the peripheral and central areas of the retina. Scotopic ERG showed a marked reduction (p < 0.0001) on the a- and b-wave amplitude and oscillatory potential (OP) complexity of the eyes subjected to EVC. These parameters were significantly (p < 0.01) restored by the application of MB. PERG indicated that EVC was responsible for a very significant decrease in N2 amplitude (p < 0.0001) and prolongation of N2 implicit time (p < 0.0001). Treatment with MB significantly restored N2 amplitude (p < 0.0001). In parallel with the ERG results, morphological analysis showed a significant loss of RGCs (p < 0.0001) and IR thickness (p < 0.0001) in both the peripheral and central retinas subjected to EVC, which was significantly prevented (p < 0.0001) by MB treatment. We have shown that MB treatment can be effective in preventing physiological and morphological hallmarks of optic neuropathy in a model of ocular hypertension, which faithfully recapitulates human open-angle glaucoma. Due to its high safety profile, this drug could therefore represent a new pharmacologic strategy to prevent vision loss in glaucoma patients.Fil: Nakamura, Ronan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Ciranna, Nicolás S.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Fernández, Juan C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Peláez, Rafael. No especifíca;Fil: Pérez Sala, Álvaro. No especifíca;Fil: Bobadilla, Miriam. No especifíca;Fil: López, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Loidl, Cesar Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Martínez, Alfredo. No especifíca;Fil: Rey Funes, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaMDPI2024-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/267438Nakamura, Ronan; Ciranna, Nicolás S.; Fernández, Juan C.; Peláez, Rafael; Pérez Sala, Álvaro; et al.; Methylene Blue Reduces Electroretinogram Distortion and Ganglion Cell Death in a Rat Model of Glaucoma; MDPI; Biomedicines; 12; 9; 9-2024; 1-152227-9059CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2227-9059/12/9/1983info:eu-repo/semantics/altIdentifier/doi/10.3390/biomedicines12091983info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-29T12:14:33Zoai:ri.conicet.gov.ar:11336/267438instacron: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:34982025-10-29 12:14:33.77CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Methylene Blue Reduces Electroretinogram Distortion and Ganglion Cell Death in a Rat Model of Glaucoma
title Methylene Blue Reduces Electroretinogram Distortion and Ganglion Cell Death in a Rat Model of Glaucoma
spellingShingle Methylene Blue Reduces Electroretinogram Distortion and Ganglion Cell Death in a Rat Model of Glaucoma
Nakamura, Ronan
DEGENERATION
GANGLION CELL
GLAUCOMA
METHYLENE BLUE
RETINA
title_short Methylene Blue Reduces Electroretinogram Distortion and Ganglion Cell Death in a Rat Model of Glaucoma
title_full Methylene Blue Reduces Electroretinogram Distortion and Ganglion Cell Death in a Rat Model of Glaucoma
title_fullStr Methylene Blue Reduces Electroretinogram Distortion and Ganglion Cell Death in a Rat Model of Glaucoma
title_full_unstemmed Methylene Blue Reduces Electroretinogram Distortion and Ganglion Cell Death in a Rat Model of Glaucoma
title_sort Methylene Blue Reduces Electroretinogram Distortion and Ganglion Cell Death in a Rat Model of Glaucoma
dc.creator.none.fl_str_mv Nakamura, Ronan
Ciranna, Nicolás S.
Fernández, Juan C.
Peláez, Rafael
Pérez Sala, Álvaro
Bobadilla, Miriam
López, Juan José
Loidl, Cesar Fabian
Martínez, Alfredo
Rey Funes, Manuel
author Nakamura, Ronan
author_facet Nakamura, Ronan
Ciranna, Nicolás S.
Fernández, Juan C.
Peláez, Rafael
Pérez Sala, Álvaro
Bobadilla, Miriam
López, Juan José
Loidl, Cesar Fabian
Martínez, Alfredo
Rey Funes, Manuel
author_role author
author2 Ciranna, Nicolás S.
Fernández, Juan C.
Peláez, Rafael
Pérez Sala, Álvaro
Bobadilla, Miriam
López, Juan José
Loidl, Cesar Fabian
Martínez, Alfredo
Rey Funes, Manuel
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DEGENERATION
GANGLION CELL
GLAUCOMA
METHYLENE BLUE
RETINA
topic DEGENERATION
GANGLION CELL
GLAUCOMA
METHYLENE BLUE
RETINA
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Glaucoma is the second leading cause of blindness worldwide and is, in most cases, a consequence of elevated intraocular pressure (IOP), ultimately resulting in the death of retinal ganglion cells (RGCs). Current treatments are mostly focused on normalizing IOP, but we propose the additional use of neuroprotective agents, including methylene blue (MB), to block the loss of RGCs. Wistar rats were subjected to episcleral vein cauterization (EVC) in the left eye while the right eye was sham-operated. One week later, they were divided into two groups, which were injected with either 2.0 mg/kg MB or phosphate-buffered saline (PBS), twice a day, for 7 days. Fifteen days after surgery, rats were tested with scotopic electroretinography (ERG) or pattern electroretinography (PERG). After sacrifice, the number of RGCs and the thickness of the inner retina (IR) were evaluated both in the peripheral and central areas of the retina. Scotopic ERG showed a marked reduction (p < 0.0001) on the a- and b-wave amplitude and oscillatory potential (OP) complexity of the eyes subjected to EVC. These parameters were significantly (p < 0.01) restored by the application of MB. PERG indicated that EVC was responsible for a very significant decrease in N2 amplitude (p < 0.0001) and prolongation of N2 implicit time (p < 0.0001). Treatment with MB significantly restored N2 amplitude (p < 0.0001). In parallel with the ERG results, morphological analysis showed a significant loss of RGCs (p < 0.0001) and IR thickness (p < 0.0001) in both the peripheral and central retinas subjected to EVC, which was significantly prevented (p < 0.0001) by MB treatment. We have shown that MB treatment can be effective in preventing physiological and morphological hallmarks of optic neuropathy in a model of ocular hypertension, which faithfully recapitulates human open-angle glaucoma. Due to its high safety profile, this drug could therefore represent a new pharmacologic strategy to prevent vision loss in glaucoma patients.
Fil: Nakamura, Ronan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Ciranna, Nicolás S.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Fernández, Juan C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Peláez, Rafael. No especifíca;
Fil: Pérez Sala, Álvaro. No especifíca;
Fil: Bobadilla, Miriam. No especifíca;
Fil: López, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Loidl, Cesar Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Martínez, Alfredo. No especifíca;
Fil: Rey Funes, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
description Glaucoma is the second leading cause of blindness worldwide and is, in most cases, a consequence of elevated intraocular pressure (IOP), ultimately resulting in the death of retinal ganglion cells (RGCs). Current treatments are mostly focused on normalizing IOP, but we propose the additional use of neuroprotective agents, including methylene blue (MB), to block the loss of RGCs. Wistar rats were subjected to episcleral vein cauterization (EVC) in the left eye while the right eye was sham-operated. One week later, they were divided into two groups, which were injected with either 2.0 mg/kg MB or phosphate-buffered saline (PBS), twice a day, for 7 days. Fifteen days after surgery, rats were tested with scotopic electroretinography (ERG) or pattern electroretinography (PERG). After sacrifice, the number of RGCs and the thickness of the inner retina (IR) were evaluated both in the peripheral and central areas of the retina. Scotopic ERG showed a marked reduction (p < 0.0001) on the a- and b-wave amplitude and oscillatory potential (OP) complexity of the eyes subjected to EVC. These parameters were significantly (p < 0.01) restored by the application of MB. PERG indicated that EVC was responsible for a very significant decrease in N2 amplitude (p < 0.0001) and prolongation of N2 implicit time (p < 0.0001). Treatment with MB significantly restored N2 amplitude (p < 0.0001). In parallel with the ERG results, morphological analysis showed a significant loss of RGCs (p < 0.0001) and IR thickness (p < 0.0001) in both the peripheral and central retinas subjected to EVC, which was significantly prevented (p < 0.0001) by MB treatment. We have shown that MB treatment can be effective in preventing physiological and morphological hallmarks of optic neuropathy in a model of ocular hypertension, which faithfully recapitulates human open-angle glaucoma. Due to its high safety profile, this drug could therefore represent a new pharmacologic strategy to prevent vision loss in glaucoma patients.
publishDate 2024
dc.date.none.fl_str_mv 2024-09
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/11336/267438
Nakamura, Ronan; Ciranna, Nicolás S.; Fernández, Juan C.; Peláez, Rafael; Pérez Sala, Álvaro; et al.; Methylene Blue Reduces Electroretinogram Distortion and Ganglion Cell Death in a Rat Model of Glaucoma; MDPI; Biomedicines; 12; 9; 9-2024; 1-15
2227-9059
CONICET Digital
CONICET
url http://hdl.handle.net/11336/267438
identifier_str_mv Nakamura, Ronan; Ciranna, Nicolás S.; Fernández, Juan C.; Peláez, Rafael; Pérez Sala, Álvaro; et al.; Methylene Blue Reduces Electroretinogram Distortion and Ganglion Cell Death in a Rat Model of Glaucoma; MDPI; Biomedicines; 12; 9; 9-2024; 1-15
2227-9059
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.3390/biomedicines12091983
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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
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dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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reponame_str CONICET Digital (CONICET)
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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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