Details

Autor(en) / Beteiligte

• Vidal‐Villegas, Beatriz
• Di Pierdomenico, Johnny
• Antonio Miralles de Imperial‐Ollero, Juan
• Manuel Bernal‐Garro, Jose
• Paz Villegas‐Pérez, María
• Vidal‐Sanz, Manuel

Titel

Short and long term effects of NMDA‐induced retinal excitotoxicity on melanopsin and non‐melanopsin containing retinal ganglion cells

Ist Teil von

• Acta ophthalmologica (Oxford, England), 2019-12, Vol.97 (S263), p.n/a

Ort / Verlag

Malden: Wiley Subscription Services, Inc

Erscheinungsjahr

2019

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.