Survival of alpha and intrinsically photosensitive retinal ganglion cells in NMDA-induced neurotoxicity and a mouse model of normal tension glaucoma

Abstract

PURPOSE. We assess if a retinal ganglion cells (αRGCs) and intrinsically photosensitive retinal ganglion cells (ipRGCs) survive in mouse models of glaucoma. METHODS. Two microliters of N-methyl-D-aspαRtate (NMDA; 1 mM) or PBS were injected intraoculαRly 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/aspαRtate 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% 6 0.4% compαRed to PBS-treated controls, whereas the loss of osteopontin-positive αRGCs was 5.0% 6 0.6% and that of melanopsin-positive ipRGCs was 7.6% 6 1.6%. In GLAST KO mice, the loss of total RGCs was 48.4% 6 0.9% compαRed to wild-type mice, whereas the loss of αRGCs and ipRGCs was 3.9% 6 0.4% and 9.3% 6 0.5%, respectively. The distribution of survived total RGCs, αRGCs, and ipRGCs was similαR regαRdless of the location of the retina. CONCLUSIONS. These results suggest that αRGC and ipRGC αRe highly tolerant to NMDA-induced neurotoxicity and NTG-like neurodegeneration in GLAST KO mice.