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Sari Miyachi Honda, Kazuhiko Namekata, Atsuko Kimura, Xiaoli Guo, Akira Matsuda, Akira Murakami, Takayuki Harada; Survival of αRGC and ipRGC in a mouse model of glaucoma. Invest. Ophthalmol. Vis. Sci. 2019;60(9):647.
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© ARVO (1962-2015); The Authors (2016-present)
Glaucoma is a progressive optic neuropathy due to retinal ganglion cell (RGC) degeneration .Reports indicate that resistance of RGC to neurodegeneration depends on its subgroup. According to recent studies, osteopontin positive αRGC and melanopsin positive intrinsically photosensitive RGC (ipRGC) are highly tolerant to damage in optic nerve injury model in mice. However it is unknown that these RGC subtypes also survive in glaucomatous degeneration.To clarify this question, we examined the survival rates of αRGC and ipRGC in glutamate / aspartate transporter (GLAST) knockout (KO) mice, which show spontaneous RGC death and typical glaucomatous damage of the optic nerve without elevated IOP, as seen in normal tension glaucoma.
The GLAST KO mouse line was generated by the CRISPR/Cas9 system. We used wild type mice (6.5 ± 0.2 months old, 6 eyes) and GLAST KO mice (7.1 ± 0.5 months old, 6 eyes ). Mice were perfused with 4% paraformaldehyde solution, and then RGCs were detected by immunostaining in the flatmounts of retina. αRGC, ipRGC and total RGC were stained with anti-osteopontin, anti-melanopsin, and anti-RNA-binding protein with multiple splicing (RBPMS) antibodies, respectively.To determine the distribution of these cells and if there is a regional specificity of cell death by the glaucomatous damage, we counted the number of each RGC in the total of twelve regions in the retina. Three standard areas (0.04mm2) were selected based on the distance from the optic disc: the central, middle, and peripheral area (0.1 mm, 0.8 mm, and 1.5 mm from the optic disc), and those from each area: nasal, temporal, upper, and lower part of the retina. The mean number of RGCs per square millimeter was calculated.
In GLAST KO mice, the number of total RGC (RBPMS-positive cells) was decreased to 48. 4 ± 0.9% compared with wild-type mice, whereas the number of αRGC (OPN-positive cells) was decreased to 3.9 ± 0.4% and the number of ipRGC (melanopsin-positive cells) was decreased to 9.3 ± 0.5%. In addition, the distribution of survived total RGC, αRGC and ipRGC in GLAST KO mouse was similar between each area, such as nasal, temporal, upper, and lower part of the retina.
Our findings suggested that both αRGC and ipRGC are highly tolerant to glaucomatous retinal degeneration. By further elucidating the reason for this high tolerance, there is a possibility of devising a new therapeutic approach for glaucoma.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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