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 (aRGCs) 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% 6 0.4% compared to PBS-treated controls, whereas the loss of osteopontin-positive aRGCs 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% compared to wild-type mice, whereas the loss of aRGCs and ipRGCs was 3.9% 6 0.4% and 9.3% 6 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 aRGC and ipRGC are highly tolerant to NMDA-induced neurotoxicity and NTG-like neurodegeneration in GLAST KO mice.

Topical ripasudil stimulates neuroprotection and axon regeneration in adult mice following optic nerve injury

“…In our study, the neuroprotective effect of ripasudil was modest considering the suppression rate of p-p38 in the retina. We previously reported that some RGC subtypes are highly tolerant to neurotoxicity and glaucoma-like www.nature.com/scientificreports/ degeneration in glaucoma model mice 22 . Subtype-specific susceptibility to RGC death is also observed after ONC 23,24 .…”

“…Mice were perfused with Zamboni's fixative and eyes were enucleated, postfixed in Zamboni's fixative for 2 h at 4℃. Retinas were then isolated from the eyecup, incised radially into four radial pieces 22 . For immunolabeling with an RBPMS antibody, the retinas were first incubated for 2 h in a blocking solution containing 5% horse serum and 1% Triton X-100 in PBS (pH 7.4).…”

“…The retinal wholemounts were examined with a fluorescence microscope (BZ-X800; Keyence, Osaka, Japan). The density of immunopositive RGCs were obtained from four central (0.1 mm from the optic disc), four middle (0.8 mm from the optic disc), and four peripheral (1.5 mm from the optic disc) areas (0.04 mm 2 ) of each retina 22 . RGCs were counted manually by three people, blind to the treatments.…”

MicroRNA‐145‐5p targeting of TRIM2 mediates the apoptosis of retinal ganglion cells via the PI3K/AKT signaling pathway in glaucoma

“…The pathogenesis of NMDA to induce the apoptosis of RGCs is excitotoxicity 29 . Before the animal procedures, the rats were anaesthetized with ketamine (80 mg/kg) and xylazine (12 mg/kg) (Ilium, Troy Laboratories Pty.…”

Suppression of Oxidative Stress as Potential Therapeutic Approach for Normal Tension Glaucoma

“…The cell body of RGCs is located in the retina and they project their axons to the brain nuclei through the optic nerve. To date, more than 40 subtypes of RGCs have been identified and how they respond to injury has been studied in various models [1][2][3][4]. Glaucoma therapy mainly focuses on reducing IOP and this approach prevents or slows down disease progression.…”