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

• 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: 101/1; 13/51; 14/34; 631/378/1689/364; 631/378/1934; 64/60; 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
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-019-1365-z

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.