Survival of Alpha and Intrinsically Photosensitive Retinal Ganglion Cells in NMDA-Induced Neurotoxicity and a Mouse Model of Normal Tension Glaucoma

PURPOSE. We assess if alpha retinal ganglion cells (alpha RGCs) and intrinsically photosensitive retinal ganglion cells (ipRGCs) survive in mouse models of glaucoma. METHODS. Two microliters of N-methyl-D-aspartate (NMDA; 1 mM) or PBS were injected intraocularly 7 days before sacrifice. Immunohistochemical analyses of the retina were performed using antibodies against RNA-binding protein with multiple splicing (RBPMS), osteopontin, and melanopsin. Immunohistochemical analyses also were performed in adult mice with glutamate/aspartate transporter (GLAST) deletion (GLAST knockout [KO] mice), a mouse model of normal tension glaucoma. RESULTS. NMDA-induced loss of RBPMS-positive total RGCs was 58.4% +/- 0.4% compared to PBS-treated controls, whereas the loss of osteopontin-positive alpha RGCs was 5.0% +/- 0.6% and that of melanopsin-positive ipRGCs was 7.6% +/- 1.6%. In GLAST KO mice, the loss of total RGCs was 48.4% +/- 0.9% compared to wild-type mice, whereas the loss of aRGCs and ipRGCs was 3.9% +/- 0.4% and 9.3% +/- 0.5%, respectively. The distribution of survived total RGCs, aRGCs, and ipRGCs was similar regardless of the location of the retina. CONCLUSIONS. These results suggest that alpha RGC and ipRGC are highly tolerant to NMDA-induced neurotoxicity and NTG-like neurodegeneration in GLAST KO mice.