Melanopsin-expressing retinal ganglion cells are relatively resistant to excitotoxicity induced by N-methyl-d-aspartate

Excitotoxicity plays an important role in neuronal loss in glaucoma. Previous studies indicate melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are more injury-resistant. However, whether melanopsin-expressing ipRGCs are resistant to N-methyl-d-aspartate (NMDA) induced excitotoxicity is not well understood. In the present study, we investigated the effects of NMDA-induced excitotoxicity in conventional retinal ganglion cells (RGCs) and melanopsin-expressing ipRGCs in adult mice. The loss of RGCs and the reduction of the thickness of inner plexiform layer (IPL) were studied by histology, immunofluorescence, TUNEL assay and optical coherence tomography (OCT). The remaining conventional RGCs and ipRGCs were quantified on the 1st, 3rd, 7th, and 21st day after NMDA injection using immunofluorescence. NMDA mediated acute and severe damage of conventional RGCs damage in a time-dependent manner, and approximately 85% of the conventional RGCs were lost on the 21st days. Furthermore, a significant reduction of the IPL thickness was observed. Moreover, compared to the PBS-injected eyes, the density of total melanopsin-positive RGCs decreased by 25% on the 1st day after NMDA injection, and then the density was constant at other time points. Our results suggest that melanopsin-expressing ipRGCs are relatively resistant to excitotoxicity induced by NMDA.