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Short and long term effects of NMDA‐induced retinal excitotoxicity on melanopsin and non‐melanopsin containing retinal ganglion cells
Author(s) -
VidalVillegas Beatriz,
Di Pierdomenico Johnny,
Antonio Miralles de ImperialOllero Juan,
Manuel BernalGarro Jose,
Paz VillegasPérez María,
VidalSanz Manuel
Publication year - 2019
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2019.5408
Subject(s) - melanopsin , retinal , population , excitotoxicity , neuroscience , biology , retina , ophthalmology , intrinsically photosensitive retinal ganglion cells , nmda receptor , retinal ganglion cell , medicine , biochemistry , photopigment , receptor , environmental health
Purpose To study short and long term responses of the population of RGCs expressing Brn3a (Brn3a + RGCs) and the population of intrinsically photosensitive RGCs expressing melanopsin (m + RGCs) to excitotoxicity induced by intravitreal injection of N‐methyl‐D‐Aspartate (NMDA). Methods In adult albino Sprague Dawley rats, the left eye received an intraocular injection of 100nM NMDA and the retinas were analyzed 3 (n=9), 7 (n=6), 14 (n=10) days (d) or 15 (n=23) months (m) later. Spectral Domain Optical Coherence Tomography (SD‐OCT; Spectralis, Heidelberg) was used to image and analyze retinal thickness longitudinally in vivo at short (3 m; n=18) and long (15 m; n=18) survival intervals. Ex vivo, retinal whole mounts were immunodetected with antibodies against Brn3a and melanopsin and the numbers of surviving Brn3a + RGCs and of m + RGCs were automatically counted and represented using isodensity or neighbour maps. Results Intraocular injection of 100nM NMDA causes a massive loss of Brn3a + RGCs; at 3 and 14 days Brn3a + RGCs numbers diminished to 50% and 25%respectively, but there was no further loss up to 15 months. However, m + RGCs showed 3 d after injection a transient downregulation of melanopsin that recovered shortly and by 14 d and at the end of the study (15 m) the numbers of m + RGCs were comparable to their contralateral fellow eyes. SD‐OCT examination showed important reductions of the total and inner retinal thicknesses at 3 m that progressed further up to 15 m. Conclusion The population of Brn3a + RGCs is quite sensitive to NMDA‐induced excitotoxicity that causes rapidly the loss of approximately 75% of these neurons. In contrast, m + RGCs appear fully resistant to NMDA‐induced excitotoxicity and show only a downregulation of melanopsin expression during the first two weeks. SD‐OCT can be used to assess retinal toxicity revealed by important reductions in total and inner retinal thickness at 3 m progressing up to 15 m.