Publication:
Evaluation of the neuroprotective efficacy of the gramine derivative ITH12657 against NMDA-induced excitotoxicity in the rat retina

Simple item page
dc.contributor.authorDi Pierdomenico, Johnny
dc.contributor.authorGallego Ortega, Alejandro
dc.contributor.authorNorte Muñoz, María
dc.contributor.authorVidal-Villegas, Beatriz
dc.contributor.authorBravo, Isaac
dc.contributor.authorBoluda-Ruiz, María
dc.contributor.authorBernal-Garro, José Manuel
dc.contributor.authorFernández-Bueno, Iván
dc.contributor.authorPastor-Jimeno, Jose Carlos
dc.contributor.authorVillegas Pérez, Maria Paz
dc.contributor.authorAvilés Trigueros, Marcelino
dc.contributor.authorRíos, Cristobal de los
dc.contributor.authorVidal Sanz, Manuel
dc.contributor.departmentOftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
dc.contributor.otherFacultad de Óptica y Optometría
dc.date.accessioned2026-01-29T09:47:06Z
dc.date.available2026-01-29T09:47:06Z
dc.date.copyright© 2024, Di Pierdomenico, Gallego-Ortega, Norte-Muñoz, Vidal-Villegas, Bravo, Boluda Ruiz, Bernal-Garro, Fernandez-Bueno, Pastor-Jimeno, Villegas-Pérez, Avilés Trigueros
dc.date.issued2024-02-13
dc.description.abstractPurpose: The aim of this study was to investigate, the neuroprotective effects of a new Gramine derivative named: ITH12657, in a model of retinal excitotoxicity induced by intravitreal injection of NMDA. Methods: Adult Sprague Dawley rats received an intravitreal injection of 100 mM NMDA in their left eye and were treated daily with subcutaneous injections of ITH12657 or vehicle. The best dose–response, therapeutic window study, and optimal treatment duration of ITH12657 were studied. Based on the best survival of Brn3a + RGCs obtained from the above-mentioned studies, the protective effects of ITH12657 were studied in vivo (retinal thickness and full-field Electroretinography), and ex vivo by quantifying the surviving population of Brn3a + RGCs, αRGCs and their subtypes α-ONsRGCs, α-ONtRGCs, and α-OFFRGCs. Results: Administration of 10 mg/kg ITH12657, starting 12 h before NMDA injection and dispensed for 3 days, resulted in the best significant protection of Brn3a + RGCs against NMDA-induced excitotoxicity. In vivo, ITH12657-treated rats showed significant preservation of retinal thickness and functional protection against NMDA-induced retinal excitotoxicity. Ex vivo results showed that ITH12657 afforded a significant protection against NMDA-induced excitotoxicity for the populations of Brn3a + RGC, αRGC, and αONs-RGC, but not for the population of αOFF-RGC, while the population of α-ONtRGC was fully resistant to NMDA-induced excitotoxicity. Conclusion: Subcutaneous administration of ITH12657 at 10 mg/kg, initiated 12 h before NMDA-induced retinal injury and continued for 3 days, resulted in the best protection of Brn3a + RGCs, αRGC, and αONs-RGC against excitotoxicity-induced RGC death. The population of αOFF-RGCs was extremely sensitive while α-ONtRGCs were fully resistant to NMDA-induced excitotoxicity.
dc.formatapplication/pdf
dc.format.extent21
dc.identifier.citationFront. Neuroanat. 18:1335176
dc.identifier.doihttps://doi.org/10.3389/fnana.2024.1335176
dc.identifier.eissn1662-5129
dc.identifier.urihttp://hdl.handle.net/10201/196609
dc.languageeng
dc.publisherFrontiers Media
dc.relationThis research was funded by PID2019-106498GB-I00 funded by Ministerio de Ciencia, Innovación y Universidades (MCIN)/AEI/ 10.13039/501100 011033 to MV-S and MA-T; (RetiBrain) ED2018-102499-T to MV-S; and by the Instituto de Salud Carlos III (PI19/01724 to CdlR) and co-funded with the European Regional Development Fund (ERDF) within the “Plan Estatal de Investigación Científica y Técnica y de Innovación 2017–2020” (FIS/PI 18–00754) to MV-P.
dc.relation.publisherversionhttps://www.frontiersin.org/journals/neuroanatomy/articles/10.3389/fnana.2024.1335176/full
dc.rightsAttribution 4.0 International*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectGlaucoma
dc.subjectRetina ganglion cell
dc.subjectNeuroprotection
dc.subjectBrn3a + RGCs
dc.subjectSD-OCT
dc.subjectαRGCs
dc.subjectRetina calcium blocker
dc.subjectNMDA excitotoxicity
dc.subject.odsNo relacionado con ningún objetivo de desarrollo sostenible
dc.titleEvaluation of the neuroprotective efficacy of the gramine derivative ITH12657 against NMDA-induced excitotoxicity in the rat retina
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublicationes
relation.isAuthorOfPublicationc94f7903-489d-4197-9272-986dca3b98a2
relation.isAuthorOfPublication929921eb-07cb-479d-8c7a-7db2d04f31c0
relation.isAuthorOfPublication73be0474-d9b3-4fd0-a880-a1be5fe75142
relation.isAuthorOfPublication67ee4a40-a760-4932-9422-ddefd0368452
relation.isAuthorOfPublication03e0f62a-075d-49de-ac29-6b4c980af0b1
relation.isAuthorOfPublication8cc42adf-31e9-49c4-a5e2-476346abe217
relation.isAuthorOfPublication.latestForDiscoveryc94f7903-489d-4197-9272-986dca3b98a2
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
fnana-18-1335176.pdf
Size:
5.81 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.37 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Artículos