Preprint Article Version 1 This version is not peer-reviewed

Melanopsin+RGCs Are Fully Resistant to NMDA-Induced Excitotoxicity

Version 1 : Received: 21 May 2019 / Approved: 23 May 2019 / Online: 23 May 2019 (04:43:45 CEST)

A peer-reviewed article of this Preprint also exists.

Vidal-Villegas, B.; Di Pierdomenico, J.; Miralles de Imperial-Ollero, J.A.; Ortín-Martínez, A.; Nadal-Nicolás, F.M.; Bernal-Garro, J.M.; Cuenca Navarro, N.; Villegas-Pérez, M.P.; Vidal-Sanz, M. Melanopsin+RGCs Are fully Resistant to NMDA-Induced Excitotoxicity. Int. J. Mol. Sci. 2019, 20, 3012. Vidal-Villegas, B.; Di Pierdomenico, J.; Miralles de Imperial-Ollero, J.A.; Ortín-Martínez, A.; Nadal-Nicolás, F.M.; Bernal-Garro, J.M.; Cuenca Navarro, N.; Villegas-Pérez, M.P.; Vidal-Sanz, M. Melanopsin+RGCs Are fully Resistant to NMDA-Induced Excitotoxicity. Int. J. Mol. Sci. 2019, 20, 3012.

Journal reference: Int. J. Mol. Sci. 2019, 20, 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 SD-OCT.  Ex vivo analyses were done at 3, 7, 14 days or 15 months after damage. Whole-mounted retinas were immunolabelled for Brn3a and melanopsin, 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±3,572 and 2,358±144 (mean ± SD; n=10), respectively. In the NMDA injected retinas, Brn3a+RGCs numbers diminished to 50% and 25%, at 3 and 14 days, respectively, but there was no further loss up to 15 months. The number of immunoidentified m+RGCs decreased significantly at 3 days, recovered between 3-7 days and was back to normal thereafter. OCT measurements revealed a significant thinning of the left retinas at 3 and 15 months. Intravitreal injections of NMDA induce a rapid loss of 75% of Brn3a+RGCs, a transient downregulation of melanopsin expression but not m+RGC death, and a thinning of the inner retinal layers.

Subject Areas

NMDA; excitotoxicity; Glaucoma; melanopsin-RGCs; intrinsically photosensitive-RGCs; Brn3a+RGCs; adult albino rat; retina; SD-OCT

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