Melanopsin(+)RGCs Are fully Resistant to NMDA-Induced Excitotoxicity.

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...

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Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
Repositorio:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
OAI Identifier:oai:isabial.fundanetsuite.com:p6347
Acceso en línea:https://isabial.portalinvestigacion.com/publicaciones6347
Access Level:acceso abierto
Palabra clave:Brn3a+RGCs
NMDA
SD-OCT
adult albino rat
excitotoxicity
glaucoma
intrinsically photosensitive-RGCs
melanopsin-RGCs
retina
Descripción
Sumario: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.