Differential effects of N-acetylcysteine on retinal degeneration in two mouse models of normal tension glaucoma

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,...

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Bibliographic Details
Published in:Cell death & disease 2019-01, Vol.10 (2), p.75-75, Article 75
Main Authors: Sano, Hiroki, Namekata, Kazuhiko, Kimura, Atsuko, Shitara, Hiroshi, Guo, Xiaoli, Harada, Chikako, Mitamura, Yoshinori, Harada, Takayuki
Format: Article
Language:English
Subjects:
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Acetylcysteine
Acetylcysteine - pharmacology
Acetylcysteine - therapeutic use
Animal models
Animals
Antibodies
Autophagy
Biochemistry
Biomedical and Life Sciences
Cell Biology
Cell Culture
Disease Models, Animal
Free Radical Scavengers - pharmacology
Free Radical Scavengers - therapeutic use
Glaucoma
Glaucoma - complications
Glaucoma - drug therapy
Glial cells
Glutathione
Humans
Immunology
Life Sciences
Mice
Nerves
Neurodegeneration
Neurodegenerative diseases
Neuronal-glial interactions
Overdose
Oxidative stress
Paracetamol
Phagocytosis
Retina
Retinal degeneration
Retinal Degeneration - drug therapy
Retinal ganglion cells
Rodents
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Summary: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.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-019-1365-z