Evaluation of the neuroprotective efficacy of the gramine derivative ITH12657 against NMDA-induced excitotoxicity in the rat retina
PurposeThe 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.MethodsAdult Sprague Dawley rats received an intravitreal injection of 100 mM NMDA in their left ey...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Neuroanatomy |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnana.2024.1335176/full |
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| author | Johnny Di Pierdomenico Alejandro Gallego-Ortega María Norte-Muñoz Beatriz Vidal-Villegas Isaac Bravo Isaac Bravo María Boluda-Ruiz Jose Manuel Bernal-Garro Iván Fernandez-Bueno Jose Carlos Pastor-Jimeno María Paz Villegas-Pérez Marcelino Avilés-Trigueros Cristobal de los Ríos Cristobal de los Ríos Manuel Vidal-Sanz |
| author_facet | Johnny Di Pierdomenico Alejandro Gallego-Ortega María Norte-Muñoz Beatriz Vidal-Villegas Isaac Bravo Isaac Bravo María Boluda-Ruiz Jose Manuel Bernal-Garro Iván Fernandez-Bueno Jose Carlos Pastor-Jimeno María Paz Villegas-Pérez Marcelino Avilés-Trigueros Cristobal de los Ríos Cristobal de los Ríos Manuel Vidal-Sanz |
| author_sort | Johnny Di Pierdomenico |
| collection | DOAJ |
| description | PurposeThe 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.MethodsAdult 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.ResultsAdministration 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.ConclusionSubcutaneous 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. |
| first_indexed | 2024-03-08T02:41:56Z |
| format | Article |
| id | doaj.art-e6efdf246d1f4f608e8f4701b382fe5d |
| institution | Directory Open Access Journal |
| issn | 1662-5129 |
| language | English |
| last_indexed | 2024-03-08T02:41:56Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroanatomy |
| spelling | doaj.art-e6efdf246d1f4f608e8f4701b382fe5d2024-02-13T13:42:08ZengFrontiers Media S.A.Frontiers in Neuroanatomy1662-51292024-02-011810.3389/fnana.2024.13351761335176Evaluation of the neuroprotective efficacy of the gramine derivative ITH12657 against NMDA-induced excitotoxicity in the rat retinaJohnny Di Pierdomenico0Alejandro Gallego-Ortega1María Norte-Muñoz2Beatriz Vidal-Villegas3Isaac Bravo4Isaac Bravo5María Boluda-Ruiz6Jose Manuel Bernal-Garro7Iván Fernandez-Bueno8Jose Carlos Pastor-Jimeno9María Paz Villegas-Pérez10Marcelino Avilés-Trigueros11Cristobal de los Ríos12Cristobal de los Ríos13Manuel Vidal-Sanz14Departamento de Oftalmología, Universidad de Murcia e IMIB-Arrixaca, Murcia, SpainDepartamento de Oftalmología, Universidad de Murcia e IMIB-Arrixaca, Murcia, SpainDepartamento de Oftalmología, Universidad de Murcia e IMIB-Arrixaca, Murcia, SpainDepartamento de Oftalmología, Universidad de Murcia e IMIB-Arrixaca, Murcia, SpainInstituto de Investigación Sanitaria, Hospital Universitario de la Princesa, Madrid, SpainDepartamento de Ciencias Básicas de la Salud, Universidad Rey Juan Carlos, Alcorcón, SpainDepartamento de Oftalmología, Universidad de Murcia e IMIB-Arrixaca, Murcia, SpainDepartamento de Oftalmología, Universidad de Murcia e IMIB-Arrixaca, Murcia, SpainInstituto Universitario de Oftalmobiología Aplicada (IOBA), Retina Group, Universidad de Valladolid, Valladolid, SpainInstituto Universitario de Oftalmobiología Aplicada (IOBA), Retina Group, Universidad de Valladolid, Valladolid, SpainDepartamento de Oftalmología, Universidad de Murcia e IMIB-Arrixaca, Murcia, SpainDepartamento de Oftalmología, Universidad de Murcia e IMIB-Arrixaca, Murcia, SpainInstituto de Investigación Sanitaria, Hospital Universitario de la Princesa, Madrid, SpainDepartamento de Ciencias Básicas de la Salud, Universidad Rey Juan Carlos, Alcorcón, SpainDepartamento de Oftalmología, Universidad de Murcia e IMIB-Arrixaca, Murcia, SpainPurposeThe 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.MethodsAdult 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.ResultsAdministration 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.ConclusionSubcutaneous 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.https://www.frontiersin.org/articles/10.3389/fnana.2024.1335176/fullNMDA excitotoxicityglaucomaretina ganglion cellneuroprotectionBrn3a + RGCsSD-OCT |
| spellingShingle | Johnny Di Pierdomenico Alejandro Gallego-Ortega María Norte-Muñoz Beatriz Vidal-Villegas Isaac Bravo Isaac Bravo María Boluda-Ruiz Jose Manuel Bernal-Garro Iván Fernandez-Bueno Jose Carlos Pastor-Jimeno María Paz Villegas-Pérez Marcelino Avilés-Trigueros Cristobal de los Ríos Cristobal de los Ríos Manuel Vidal-Sanz Evaluation of the neuroprotective efficacy of the gramine derivative ITH12657 against NMDA-induced excitotoxicity in the rat retina Frontiers in Neuroanatomy NMDA excitotoxicity glaucoma retina ganglion cell neuroprotection Brn3a + RGCs SD-OCT |
| title | Evaluation of the neuroprotective efficacy of the gramine derivative ITH12657 against NMDA-induced excitotoxicity in the rat retina |
| title_full | Evaluation of the neuroprotective efficacy of the gramine derivative ITH12657 against NMDA-induced excitotoxicity in the rat retina |
| title_fullStr | Evaluation of the neuroprotective efficacy of the gramine derivative ITH12657 against NMDA-induced excitotoxicity in the rat retina |
| title_full_unstemmed | Evaluation of the neuroprotective efficacy of the gramine derivative ITH12657 against NMDA-induced excitotoxicity in the rat retina |
| title_short | Evaluation of the neuroprotective efficacy of the gramine derivative ITH12657 against NMDA-induced excitotoxicity in the rat retina |
| title_sort | evaluation of the neuroprotective efficacy of the gramine derivative ith12657 against nmda induced excitotoxicity in the rat retina |
| topic | NMDA excitotoxicity glaucoma retina ganglion cell neuroprotection Brn3a + RGCs SD-OCT |
| url | https://www.frontiersin.org/articles/10.3389/fnana.2024.1335176/full |
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