Genetic inhibition of collapsin response mediator protein-2 phosphorylation ameliorates retinal ganglion cell death in normal-tension glaucoma models

Musukha Mala Brahma, Kazuya Takahashi, Kazuhiko Namekata, Takayuki Harada, Yoshio Goshima, Toshio Ohshima*

*この研究の対応する著者

研究成果: Article査読

1 被引用数 (Scopus)

抄録

Glaucoma is a neurodegenerative disorder caused by the death of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP) is a cause of glaucoma. However, glaucoma often develops with normal IOP and is known as normal-tension glaucoma (NTG). Glutamate neurotoxicity is considered as one of the significant causes of NTG, resulting in excessive stimulation of retinal neurons via the N-methyl-D-aspartate (NMDA) receptors. The present study examined the phosphorylation of collapsin response mediator protein-2 (CRMP2), a protein that is abundantly expressed in neurons and involved in their development. In two mouse models, NMDA-injection and glutamate/aspartate transporter (GLAST) mutant, CRMP2 phosphorylation at the cyclin-dependent kinase-5 (Cdk5) site was elevated in RGCs. We confirmed that the decrease in the number of RGCs and thickness of the inner retinal layer (IRL) could be suppressed after NMDA administration in CRMP2KI/KI mice with genetically inhibited CRMP2 phosphorylation. Next, we investigated GLAST heterozygotes (GLAST+/−) with CRMP2KI/KI (GLAST+/−;CRMP2KI/KI) and GLAST knockout (GLAST−/−) mice with CRMP2KI/KI (GLAST−/−;CRMP2KI/KI) mice and compared them with GLAST+/− and GLAST−/− mice. pCRMP2 (S522) inhibition significantly reduced RGC loss and IRL thinning. These results suggest that the inhibition of CRMP2 phosphorylation could be a novel strategy for treating NTG.

本文言語English
ページ(範囲)526-536
ページ数11
ジャーナルGenes to Cells
27
8
DOI
出版ステータスPublished - 2022 8月

ASJC Scopus subject areas

  • 遺伝学
  • 細胞生物学

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