| 研究実績の概要 |
Normal-tension glaucoma (NTG) is a heterogeneous disease characterized by RGC death leading to cupping of the optic nerve head and visual field loss at normal IOP. The pathogenesis of NTG remains unclear. Here, we describe a single nucleotide mutation in exon 2 of the METTL23 gene. This mutation caused mRNA aberrant splicing, which abolished normal protein production and altered subcellular localization. Mettl23-KI mice developed a NTG phenotype. METTL23 is a histone arginine methyltransferase expressed in murine and macaque RGCs. However, the novel mutation reduced METTL23 expression in RGCs of Mettl23-KI mice. Moreover, our findings demonstrated that METTL23 catalyzed the dimethylation of H3R17 in the retina which was required for the NF-κB-mediated TNF-α and IL-1β feedback.
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