Melanopsin(+)RGCs Are fully Resistant to NMDA-Induced Excitotoxicity.
Por:
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 and Vidal-Sanz M
Publicada:
20 jun 2019
Ahead of Print:
20 jun 2019
Resumen:
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.
Filiaciones:
Vidal-Villegas B:
Department of Ophthalmology, University of Murcia and Instituto Murciano de Investigación Biosanitaria (IMIB)-Virgen de la Arrixaca, 30120 Murcia, Spain.
:
Department of Physiology, Genetics and Microbiology and Multidisciplinary Institute for Environmental Studies "Ramón Margalef", University of Alicante, 03690 Alicante, Spain.
Open Access
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