Melanopsin+RGCs Are fully Resistant to NMDA-Induced Excitotoxicity

Please use this identifier to cite or link to this item:
Información del item - Informació de l'item - Item information
Title: Melanopsin+RGCs Are fully Resistant to NMDA-Induced Excitotoxicity
Authors: Vidal-Villegas, Beatriz | Di Pierdomenico, Johnny | Miralles de Imperial-Ollero, Juan A. | Ortín Martínez, Arturo | Nadal-Nicolás, Francisco Manuel | Bernal-Garro, Jose M. | Cuenca, Nicolás | Villegas Pérez, María Paz | Vidal Sanz, Manuel
Research Group/s: Neurobiología del Sistema Visual y Terapia de Enfermedades Neurodegenerativas (NEUROVIS)
Center, Department or Service: Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología | Universidad de Alicante. Instituto Multidisciplinar para el Estudio del Medio "Ramón Margalef"
Keywords: NMDA | Excitotoxicity | Glaucoma | Melanopsin-RGCs | Intrinsically photosensitive-RGCs | Brn3a+RGCs | Adult albino rat | Retina | SD-OCT
Knowledge Area: Biología Celular
Issue Date: 20-Jun-2019
Publisher: MDPI
Citation: Vidal-Villegas B, Di Pierdomenico J, Miralles de Imperial-Ollero JA, Ortín-Martínez A, Nadal-Nicolás FM, Bernal-Garro JM, Cuenca Navarro N, Villegas-Pérez MP, Vidal-Sanz M. Melanopsin+RGCs Are fully Resistant to NMDA-Induced Excitotoxicity. International Journal of Molecular Sciences. 2019; 20(12):3012. doi:10.3390/ijms20123012
Abstract: We studied short- and long-term effects of intravitreal injection of N-methyl-d-aspartate (NMDA) on melanopsin-containing (m+) and non-melanopsin-containing (Brn3a+) retinal ganglion cells (RGCs). In adult SD-rats, the left eye received a single intravitreal injection of 5µL of 100nM NMDA. At 3 and 15 months, retinal thickness was measured in vivo using Spectral Domain-Optical Coherence Tomography (SD-OCT). Ex vivo analyses were done at 3, 7, or 14 days or 15 months after damage. Whole-mounted retinas were immunolabelled for brain-specific homeobox/POU domain protein 3A (Brn3a) and melanopsin (m), the total number of Brn3a+RGCs and m+RGCs were quantified, and their topography represented. In control retinas, the mean total numbers of Brn3a+RGCs and m+RGCs were 78,903 ± 3572 and 2358 ± 144 (mean ± SD; n = 10), respectively. In the NMDA injected retinas, Brn3a+RGCs numbers diminished to 49%, 28%, 24%, and 19%, at 3, 7, 14 days, and 15 months, respectively. There was no further loss between 7 days and 15 months. The number of immunoidentified m+RGCs decreased significantly at 3 days, recovered between 3 and 7 days, and were back to normal thereafter. OCT measurements revealed a significant thinning of the left retinas at 3 and 15 months. Intravitreal injections of NMDA induced within a week a rapid loss of 72% of Brn3a+RGCs, a transient downregulation of melanopsin expression (but not m+RGC death), and a thinning of the inner retinal layers.
Sponsor: This study was supported by the Fundación Séneca, Agencia de Ciencia y Tecnología Región de Murcia (19881/GERM/15), and the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional “una manera de hacer Europa” (SAF2015-67643-P, PI16/00380, RD16/0008/0026 and RD16/0008/0016).
ISSN: 1661-6596 (Print) | 1422-0067 (Online)
DOI: 10.3390/ijms20123012
Language: eng
Type: info:eu-repo/semantics/article
Rights: © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (
Peer Review: si
Publisher version:
Appears in Collections:INV - NEUROVIS - Artículos de Revistas

Files in This Item:
Files in This Item:
File Description SizeFormat 
Thumbnail2019_Vidal-Villegas_etal_IntJMolSci.pdf2,31 MBAdobe PDFOpen Preview

This item is licensed under a Creative Commons License Creative Commons