학술논문
Drug Treatment Attenuates Retinal Ganglion Cell Death by Inhibiting Collapsin Response Mediator Protein 2 Phosphorylation in Mouse Models of Normal Tension Glaucoma.
Document Type
Academic Journal
Author
Wang Y; Department of Life Science and Medical Bioscience, Waseda University, Shinjuku-ku, Tokyo, 162-8480, Japan.; Brahma MM; Department of Life Science and Medical Bioscience, Waseda University, Shinjuku-ku, Tokyo, 162-8480, Japan.; Takahashi K; Department of Life Science and Medical Bioscience, Waseda University, Shinjuku-ku, Tokyo, 162-8480, Japan.; Hernandez ANB; Department of Life Science and Medical Bioscience, Waseda University, Shinjuku-ku, Tokyo, 162-8480, Japan.; Ichikawa K; Department of Life Science and Medical Bioscience, Waseda University, Shinjuku-ku, Tokyo, 162-8480, Japan.; Minami S; Nara Medical University, Kashihara City, Nara, 634-8521, Japan.; Goshima Y; Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan.; Harada T; Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, 156-8506, Japan.; Ohshima T; Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo, 162-8480, Japan. ohshima@waseda.jp.
Source
Publisher: Humana Press Country of Publication: United States NLM ID: 101135365 Publication Model: Electronic Cited Medium: Internet ISSN: 1559-1174 (Electronic) Linking ISSN: 15351084 NLM ISO Abbreviation: Neuromolecular Med Subsets: MEDLINE
Subject
Language
English
Abstract
Normal tension glaucoma (NTG) is a progressive neurodegenerative disease in glaucoma families. Typical glaucoma develops because of increased intraocular pressure (IOP), whereas NTG develops despite normal IOP. As a subtype of open-angle glaucoma, NTG is characterized by retinal ganglion cell (RGC) degeneration, gradual loss of axons, and injury to the optic nerve. The relationship between glutamate excitotoxicity and oxidative stress has elicited great interest in NTG studies. We recently reported that suppressing collapsin response mediator protein 2 (CRMP2) phosphorylation in S522A CRMP2 mutant (CRMP2 KIKI) mice inhibited RGC death in NTG mouse models. This study evaluated the impact of the natural compounds huperzine A (HupA) and naringenin (NAR), which have therapeutic effects against glutamate excitotoxicity and oxidative stress, on inhibiting CMRP2 phosphorylation in mice intravitreally injected with N-methyl-D-aspartate (NMDA) and GLAST mutant mice. Results of the study demonstrated that HupA and NAR significantly reduced RGC degeneration and thinning of the inner retinal layer, and inhibited the elevated CRMP2 phosphorylation. These treatments protected against glutamate excitotoxicity and suppressed oxidative stress, which could provide insight into developing new effective therapeutic strategies for NTG.
(© 2024. The Author(s).)
(© 2024. The Author(s).)