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Melanopsin+RGCs Are fully Resistant to NMDA-Induced Excitotoxicity.
Int J Mol Sci. 2019 Jun 20; 20(12)IJ

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.

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Authors+Show Affiliations

Vidal-Villegas B
Department of Ophthalmology, University of Murcia and Instituto Murciano de Investigación Biosanitaria (IMIB)-Virgen de la Arrixaca, 30120 Murcia, Spain. beatrizvidalvillegas@gmail.com.
Di Pierdomenico J
Department of Ophthalmology, University of Murcia and Instituto Murciano de Investigación Biosanitaria (IMIB)-Virgen de la Arrixaca, 30120 Murcia, Spain. johnnydp@um.es.
Miralles de Imperial-Ollero JA
Department of Ophthalmology, University of Murcia and Instituto Murciano de Investigación Biosanitaria (IMIB)-Virgen de la Arrixaca, 30120 Murcia, Spain. juanantonio.miralles@um.es.
Ortín-Martínez A
Department of Ophthalmology, University of Murcia and Instituto Murciano de Investigación Biosanitaria (IMIB)-Virgen de la Arrixaca, 30120 Murcia, Spain. Arturo.OrtinMartinez@uhnresearch.ca.
Nadal-Nicolás FM
Department of Ophthalmology, University of Murcia and Instituto Murciano de Investigación Biosanitaria (IMIB)-Virgen de la Arrixaca, 30120 Murcia, Spain. fm.nadalnicolas@um.es.
Bernal-Garro JM
Department of Ophthalmology, University of Murcia and Instituto Murciano de Investigación Biosanitaria (IMIB)-Virgen de la Arrixaca, 30120 Murcia, Spain. jmbg@um.es.
Cuenca Navarro N
Department of Physiology, Genetics and Microbiology and Multidisciplinary Institute for Environmental Studies "Ramón Margalef", University of Alicante, 03690 Alicante, Spain. cuenca@ua.es.
Villegas-Pérez MP
Department of Ophthalmology, University of Murcia and Instituto Murciano de Investigación Biosanitaria (IMIB)-Virgen de la Arrixaca, 30120 Murcia, Spain. mpville@um.es.
Vidal-Sanz M
Department of Ophthalmology, University of Murcia and Instituto Murciano de Investigación Biosanitaria (IMIB)-Virgen de la Arrixaca, 30120 Murcia, Spain. manuel.vidal@um.es.

MeSH

AnimalsCell CountFemaleIntravitreal InjectionsN-MethylaspartateRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateRetinal Ganglion CellsRod OpsinsTranscription Factor Brn-3A

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31226772

Citation

Vidal-Villegas, Beatriz, et al. "Melanopsin+RGCs Are Fully Resistant to NMDA-Induced Excitotoxicity." International Journal of Molecular Sciences, vol. 20, no. 12, 2019.
Vidal-Villegas B, Di Pierdomenico J, Miralles de Imperial-Ollero JA, et al. Melanopsin+RGCs Are fully Resistant to NMDA-Induced Excitotoxicity. Int J Mol Sci. 2019;20(12).
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. (2019). Melanopsin+RGCs Are fully Resistant to NMDA-Induced Excitotoxicity. International Journal of Molecular Sciences, 20(12). https://doi.org/10.3390/ijms20123012
Vidal-Villegas B, et al. Melanopsin+RGCs Are Fully Resistant to NMDA-Induced Excitotoxicity. Int J Mol Sci. 2019 Jun 20;20(12) PubMed PMID: 31226772.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Melanopsin+RGCs Are fully Resistant to NMDA-Induced Excitotoxicity. AU - Vidal-Villegas,Beatriz, AU - Di Pierdomenico,Johnny, AU - Miralles de Imperial-Ollero,Juan A, AU - Ortín-Martínez,Arturo, AU - Nadal-Nicolás,Francisco M, AU - Bernal-Garro,Jose M, AU - Cuenca Navarro,Nicolás, AU - Villegas-Pérez,María P, AU - Vidal-Sanz,Manuel, Y1 - 2019/06/20/ PY - 2019/05/19/received PY - 2019/06/11/revised PY - 2019/06/18/accepted PY - 2019/6/23/entrez PY - 2019/6/23/pubmed PY - 2019/12/18/medline KW - Brn3a+RGCs KW - NMDA KW - SD-OCT KW - adult albino rat KW - excitotoxicity KW - glaucoma KW - intrinsically photosensitive-RGCs KW - melanopsin-RGCs KW - retina JF - International journal of molecular sciences JO - Int J Mol Sci VL - 20 IS - 12 N2 - 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. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/31226772/Melanopsin+RGCs_Are_fully_Resistant_to_NMDA_Induced_Excitotoxicity_ DB - PRIME DP - Unbound Medicine ER -