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

Autor:	Di Pierdomenico J; Departamento de Oftalmología, Universidad de Murcia e IMIB-Arrixaca, Murcia, Spain., Gallego-Ortega A; Departamento de Oftalmología, Universidad de Murcia e IMIB-Arrixaca, Murcia, Spain., Norte-Muñoz M; Departamento de Oftalmología, Universidad de Murcia e IMIB-Arrixaca, Murcia, Spain., Vidal-Villegas B; Departamento de Oftalmología, Universidad de Murcia e IMIB-Arrixaca, Murcia, Spain., Bravo I; Instituto de Investigación Sanitaria, Hospital Universitario de la Princesa, Madrid, Spain.; Departamento de Ciencias Básicas de la Salud, Universidad Rey Juan Carlos, Alcorcón, Spain., Boluda-Ruiz M; Departamento de Oftalmología, Universidad de Murcia e IMIB-Arrixaca, Murcia, Spain., Bernal-Garro JM; Departamento de Oftalmología, Universidad de Murcia e IMIB-Arrixaca, Murcia, Spain., Fernandez-Bueno I; Instituto Universitario de Oftalmobiología Aplicada (IOBA), Retina Group, Universidad de Valladolid, Valladolid, Spain., Pastor-Jimeno JC; Instituto Universitario de Oftalmobiología Aplicada (IOBA), Retina Group, Universidad de Valladolid, Valladolid, Spain., Villegas-Pérez MP; Departamento de Oftalmología, Universidad de Murcia e IMIB-Arrixaca, Murcia, Spain., Avilés-Trigueros M; Departamento de Oftalmología, Universidad de Murcia e IMIB-Arrixaca, Murcia, Spain., de Los Ríos C; Instituto de Investigación Sanitaria, Hospital Universitario de la Princesa, Madrid, Spain.; Departamento de Ciencias Básicas de la Salud, Universidad Rey Juan Carlos, Alcorcón, Spain., Vidal-Sanz M; Departamento de Oftalmología, Universidad de Murcia e IMIB-Arrixaca, Murcia, Spain.
Jazyk:	angličtina
Zdroj:	Frontiers in neuroanatomy [Front Neuroanat] 2024 Feb 13; Vol. 18, pp. 1335176. Date of Electronic Publication: 2024 Feb 13 (Print Publication: 2024).
DOI:	10.3389/fnana.2024.1335176
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Di Pierdomenico, Gallego-Ortega, Norte-Muñoz, Vidal-Villegas, Bravo, Boluda-Ruiz, Bernal-Garro, Fernandez-Bueno, Pastor-Jimeno, Villegas-Pérez, Avilés-Trigueros, de los Ríos and Vidal-Sanz.)
Databáze:	MEDLINE
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