RT info:eu-repo/semantics/article
T1 Evaluation of the neuroprotective efficacy of the gramine derivative ITH12657 against NMDA-induced excitotoxicity in the rat retina
A1 Di Pierdomenico, Johnny
A1 Gallego-Ortega, Alejandro
A1 Norte-Muñoz, María
A1 Vidal-Villegas, Beatriz
A1 Bravo, Isaac
A1 Boluda-Ruiz, María
A1 Bernal-Garro, Jose Manuel
A1 Fernández Bueno, Iván
A1 Pastor Jimeno, José Carlos
A1 Villegas-Pérez, María Paz
A1 Avilés-Trigueros, Marcelino
A1 de los Ríos, Cristobal
A1 Vidal Sanz, Manuel Antón
AB Purpose: The aim of this study was to investigate, the neuroprotective effects ofa new Gramine derivative named: ITH12657, in a model of retinal excitotoxicityinduced by intravitreal injection of NMDA.Methods: Adult Sprague Dawley rats received an intravitreal injection of 100 mMNMDA in their left eye and were treated daily with subcutaneous injections ofITH12657 or vehicle. The best dose–response, therapeutic window study, andoptimal treatment duration of ITH12657 were studied. Based on the best survival ofBrn3a + RGCs obtained from the above-mentioned studies, the protective effects ofITH12657 were studied in vivo (retinal thickness and full-field Electroretinography),and ex vivo by quantifying the surviving population of Brn3a + RGCs, αRGCs andtheir subtypes α-ONsRGCs, α-ONtRGCs, and α-OFFRGCs.Results: Administration of 10 mg/kg ITH12657, starting 12 h before NMDAinjection and dispensed for 3 days, resulted in the best significant protectionof Brn3a + RGCs against NMDA-induced excitotoxicity. In vivo, ITH12657-treated rats showed significant preservation of retinal thickness and functionalprotection against NMDA-induced retinal excitotoxicity. Ex vivo results showedthat ITH12657 afforded a significant protection against NMDA-inducedexcitotoxicity for the populations of Brn3a + RGC, αRGC, and αONs-RGC, butnot for the population of αOFF-RGC, while the population of α-ONtRGC wasfully resistant to NMDA-induced excitotoxicity.Conclusion: Subcutaneous administration of ITH12657 at 10 mg/kg, initiated12 h before NMDA-induced retinal injury and continued for 3 days, resulted in thebest protection of Brn3a + RGCs, αRGC, and αONs-RGC against excitotoxicity-induced RGC death. The population of αOFF-RGCs was extremely sensitivewhile α-ONtRGCs were fully resistant to NMDA-induced excitotoxicity.
YR 2024
FD 2024
LK https://uvadoc.uva.es/handle/10324/71464
UL https://uvadoc.uva.es/handle/10324/71464
LA eng
NO Frontiers in Neuroanatomy 2024;18
NO Producción Científica
DS UVaDOC
RD 22-ene-2025