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ID 114666
Title Alternative
2種類の正常眼圧緑内障モデルマウスに対するN-アセチルシステインの網膜変性抑制効果の違い
Author
Sano, Hiroki Tokyo Metropolitan Institute of Medical Science|Tokushima University
Namekata, Kazuhiko Tokyo Metropolitan Institute of Medical Science
Kimura, Atsuko Tokyo Metropolitan Institute of Medical Science
Shitara, Hiroshi Tokyo Metropolitan Institute of Medical Science
Guo, Xiaoli Tokyo Metropolitan Institute of Medical Science
Harada, Chikako Tokyo Metropolitan Institute of Medical Science
Harada, Takayuki Tokyo Metropolitan Institute of Medical Science|Tokushima University
Keywords
N-acetylcysteine
NTG
oxidative stress
EAAC1
GLAST
Content Type
Thesis or Dissertation
Description
N-acetylcysteine (NAC) is widely used as a mucolytic agent and as an antidote to paracetamol overdose. NAC serves as a precursor of cysteine and stimulates the synthesis of glutathione in neural cells. Suppressing oxidative stress in the retina may be an effective therapeutic strategy for glaucoma, a chronic neurodegenerative disease of the retinal ganglion cells (RGCs) and optic nerves. Here we examined the therapeutic potential of NAC in two mouse models of normal tension glaucoma, in which excitatory amino-acid carrier 1 (EAAC1) or glutamate/aspartate transporter (GLAST) gene was deleted. EAAC1 is expressed in retinal neurons including RGCs, whereas GLAST is mainly expressed in Müller glial cells. Intraperitoneal administration of NAC prevented RGC degeneration and visual impairment in EAAC1-deficient (knockout; KO) mice, but not in GLAST KO mice. In EAAC1 KO mice, oxidative stress and autophagy were suppressed with increased glutathione levels by NAC treatment. Our findings suggest a possibility that systemic administration of NAC may be available for some types of glaucoma patients.
Journal Title
Cell Death & Disease
ISSN
20414889
Publisher
Springer Nature
Volume
10
Start Page
75
Published Date
2019-01-28
Remark
内容要旨・審査要旨・論文本文の公開
本論文は, 著者Hiroki Sanoの学位論文として提出され, 学位審査・授与の対象となっている。
Rights
© The Author(s) 2019
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3371号
Diploma Number
甲医第1454号
Granted Date
2020-03-23
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Medical Sciences