Abstract
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.
Highlights
Glaucoma, an optic neuropathy and a neurodegenerative disease of the eye, is the second leading cause of world blindness[1]
We found that the ganglion cell complex (GCC) thickness was reduced in control mice, but it was almost unchanged in NAC-treated excitatory amino-acid carrier 1 (EAAC1) KO mice (Fig. 1b)
In order to determine if the neuroprotective effect by NAC treatment in EAAC1 KO mice reflects functional aspects, we investigated retinal function using multifocal electroretinogram
Summary
An optic neuropathy and a neurodegenerative disease of the eye, is the second leading cause of world blindness[1]. Glaucoma is characterized by slow progressive degeneration of retinal ganglion cells (RGCs) and their axons, which are critical elements for loss of visual function. While this is usually associated with elevated intraocular pressure (IOP), there is a subtype of glaucoma termed normal tension glaucoma (NTG) that present with IOP in a statistically normal range. EAAC1 is GLAST is mainly expressed in Müller glial cells. EAAC1 transports extracellular glutamate and cysteine, which are important substrates for glutathione (GSH) synthesis, into neural cells[4,5]. GSH synthesis in Müller glial cells is considered to be important as GSH may be released from
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