Neuroprotective Effect of Methylene Blue in a Rat Model of Traumatic Optic Neuropathy

<b>Background</b>: Traumatic optic neuropathy (TON) represents a major cause of vision loss worldwide, and treatment options are limited. Here, we study whether methylene blue (MB), a free radical scavenger, is able to prevent morphological and electrophysiological hallmarks of neuropath...

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Main Authors: Nicolás S. Ciranna, Ronan Nakamura, Rafael Peláez, Álvaro Pérez-Sala, Patricia Sarrión, Juan C. Fernández, Alejandra Paganelli, Agustín P. Aranalde, Ulises P. Ruiz, Juan J. López-Costa, César F. Loidl, Alfredo Martínez, Manuel Rey-Funes
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Language:English
Published: MDPI AG 2025-06-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/6/920
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author Nicolás S. Ciranna
Ronan Nakamura
Rafael Peláez
Álvaro Pérez-Sala
Patricia Sarrión
Juan C. Fernández
Alejandra Paganelli
Agustín P. Aranalde
Ulises P. Ruiz
Juan J. López-Costa
César F. Loidl
Alfredo Martínez
Manuel Rey-Funes
author_facet Nicolás S. Ciranna
Ronan Nakamura
Rafael Peláez
Álvaro Pérez-Sala
Patricia Sarrión
Juan C. Fernández
Alejandra Paganelli
Agustín P. Aranalde
Ulises P. Ruiz
Juan J. López-Costa
César F. Loidl
Alfredo Martínez
Manuel Rey-Funes
author_sort Nicolás S. Ciranna
collection DOAJ
description <b>Background</b>: Traumatic optic neuropathy (TON) represents a major cause of vision loss worldwide, and treatment options are limited. Here, we study whether methylene blue (MB), a free radical scavenger, is able to prevent morphological and electrophysiological hallmarks of neuropathy in an animal model of TON. <b>Methods</b>: The left eyes of Wistar rats were subjected to intraorbital nerve crush (IONC) while the right ones were sham operated. The group of rats treated with MB (n = 16) received five intraperitoneal injections with 2.0 mg/kg MB in the 24 h following IONC while the control group (n = 16) received just vehicle (PBS) as a control. Twenty-one days after surgery, scotopic full field (scERG), scotopic oscillatory potentials (OP), photopic full field (phERG) and pattern (PERG) electroretinography were performed for retinal function assessment. Furthermore, the number of cell nuclei in the ganglion cell layer (GCL) was recorded in post mortem histological sections. <b>Results</b>: IONC induced very significant reductions in electrophysiological parameters including scotopic a- and b-wave, OPs, photopic b-wave, PhNR amplitude and N2 amplitude. In addition, it also generated a significant prolongation of the N2 implicit time, indicating a profound impact on retinal function. This was further corroborated by a very significant reduction in the number of neuronal nuclei in the GCL, suggesting an intense loss and functional impairment of retinal ganglion cells. MB treatment was able to prevent, partially or completely, all those parameters, indicating the efficiency of such approach. <b>Conclusions</b>: Since MB is already approved for clinical use and presents a high safety profile, it could be repurposed as a neuroprotective drug for ophthalmological applications once proper phase 2 clinical trials are accomplished.
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spelling doaj-art-9e5e23df42024a2fa8f72cd601cdd2d42025-08-20T03:16:35ZengMDPI AGPharmaceuticals1424-82472025-06-0118692010.3390/ph18060920Neuroprotective Effect of Methylene Blue in a Rat Model of Traumatic Optic NeuropathyNicolás S. Ciranna0Ronan Nakamura1Rafael Peláez2Álvaro Pérez-Sala3Patricia Sarrión4Juan C. Fernández5Alejandra Paganelli6Agustín P. Aranalde7Ulises P. Ruiz8Juan J. López-Costa9César F. Loidl10Alfredo Martínez11Manuel Rey-Funes12Institute of Cell Biology and Neurosciences “Prof. E. de Robertis”, Faculty of Medicine, University of Buenos Aires, Buenos Aires 1821, ArgentinaInstitute of Cell Biology and Neurosciences “Prof. E. de Robertis”, Faculty of Medicine, University of Buenos Aires, Buenos Aires 1821, ArgentinaBiomarkers and Molecular Signaling Group, Neurodegenerative Diseases Area, Center for Biomedical Research of La Rioja (CIBIR), 26006 Logroño, SpainBiomarkers and Molecular Signaling Group, Neurodegenerative Diseases Area, Center for Biomedical Research of La Rioja (CIBIR), 26006 Logroño, SpainBiomarkers and Molecular Signaling Group, Neurodegenerative Diseases Area, Center for Biomedical Research of La Rioja (CIBIR), 26006 Logroño, SpainInstitute of Cell Biology and Neurosciences “Prof. E. de Robertis”, Faculty of Medicine, University of Buenos Aires, Buenos Aires 1821, ArgentinaInstitute of Cell Biology and Neurosciences “Prof. E. de Robertis”, Faculty of Medicine, University of Buenos Aires, Buenos Aires 1821, ArgentinaInstitute of Cell Biology and Neurosciences “Prof. E. de Robertis”, Faculty of Medicine, University of Buenos Aires, Buenos Aires 1821, ArgentinaInstitute of Cell Biology and Neurosciences “Prof. E. de Robertis”, Faculty of Medicine, University of Buenos Aires, Buenos Aires 1821, ArgentinaInstitute of Cell Biology and Neurosciences “Prof. E. de Robertis”, Faculty of Medicine, University of Buenos Aires, Buenos Aires 1821, ArgentinaInstitute of Cell Biology and Neurosciences “Prof. E. de Robertis”, Faculty of Medicine, University of Buenos Aires, Buenos Aires 1821, ArgentinaAngiogenesis Group, Oncology Area, Center for Biomedical Research of La Rioja (CIBIR), 26006 Logroño, SpainInstitute of Cell Biology and Neurosciences “Prof. E. de Robertis”, Faculty of Medicine, University of Buenos Aires, Buenos Aires 1821, Argentina<b>Background</b>: Traumatic optic neuropathy (TON) represents a major cause of vision loss worldwide, and treatment options are limited. Here, we study whether methylene blue (MB), a free radical scavenger, is able to prevent morphological and electrophysiological hallmarks of neuropathy in an animal model of TON. <b>Methods</b>: The left eyes of Wistar rats were subjected to intraorbital nerve crush (IONC) while the right ones were sham operated. The group of rats treated with MB (n = 16) received five intraperitoneal injections with 2.0 mg/kg MB in the 24 h following IONC while the control group (n = 16) received just vehicle (PBS) as a control. Twenty-one days after surgery, scotopic full field (scERG), scotopic oscillatory potentials (OP), photopic full field (phERG) and pattern (PERG) electroretinography were performed for retinal function assessment. Furthermore, the number of cell nuclei in the ganglion cell layer (GCL) was recorded in post mortem histological sections. <b>Results</b>: IONC induced very significant reductions in electrophysiological parameters including scotopic a- and b-wave, OPs, photopic b-wave, PhNR amplitude and N2 amplitude. In addition, it also generated a significant prolongation of the N2 implicit time, indicating a profound impact on retinal function. This was further corroborated by a very significant reduction in the number of neuronal nuclei in the GCL, suggesting an intense loss and functional impairment of retinal ganglion cells. MB treatment was able to prevent, partially or completely, all those parameters, indicating the efficiency of such approach. <b>Conclusions</b>: Since MB is already approved for clinical use and presents a high safety profile, it could be repurposed as a neuroprotective drug for ophthalmological applications once proper phase 2 clinical trials are accomplished.https://www.mdpi.com/1424-8247/18/6/920optic neuropathytraumaneuroprotectionmethylene blueelectroretinographyretinal ganglion cells
spellingShingle Nicolás S. Ciranna
Ronan Nakamura
Rafael Peláez
Álvaro Pérez-Sala
Patricia Sarrión
Juan C. Fernández
Alejandra Paganelli
Agustín P. Aranalde
Ulises P. Ruiz
Juan J. López-Costa
César F. Loidl
Alfredo Martínez
Manuel Rey-Funes
Neuroprotective Effect of Methylene Blue in a Rat Model of Traumatic Optic Neuropathy
Pharmaceuticals
optic neuropathy
trauma
neuroprotection
methylene blue
electroretinography
retinal ganglion cells
title Neuroprotective Effect of Methylene Blue in a Rat Model of Traumatic Optic Neuropathy
title_full Neuroprotective Effect of Methylene Blue in a Rat Model of Traumatic Optic Neuropathy
title_fullStr Neuroprotective Effect of Methylene Blue in a Rat Model of Traumatic Optic Neuropathy
title_full_unstemmed Neuroprotective Effect of Methylene Blue in a Rat Model of Traumatic Optic Neuropathy
title_short Neuroprotective Effect of Methylene Blue in a Rat Model of Traumatic Optic Neuropathy
title_sort neuroprotective effect of methylene blue in a rat model of traumatic optic neuropathy
topic optic neuropathy
trauma
neuroprotection
methylene blue
electroretinography
retinal ganglion cells
url https://www.mdpi.com/1424-8247/18/6/920
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