Publication: Evaluation of the neuroprotective efficacy of the gramine derivative ITH12657 against NMDA-induced excitotoxicity in the rat retina
Authors
Di Pierdomenico Spitilli, J. ; Gallego Ortega, A. ; Norte Muñoz, M. ; Vidal Villegas, B. ; Bravo, I. ; Boluda-ruiz, M. ; Bernal Garro, J. M. ; Fernandez-Bueno, I. ; Pastor Jimeno, J. C. ; Villegas Perez, M. P. ; Aviles Trigueros, M. ; De Los Ríos, C. ; Vidal Sanz, M. A.
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Publisher
Frontiers Media
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DOI
https://doi.org/10.3389/fnana.2024.1335176
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info:eu-repo/semantics/article
Description
© 2024. The authors. This document is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by /4.0/
This document is the published version of a published work that appeared in final form in Frontiers in Neuroanatomy
Abstract
Purpose: 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.
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Citation
Frontiers in Neuroanatomy 18:1335176
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