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Citations to this article

The potential role of glutamate transporters in the pathogenesis of normal tension glaucoma
Takayuki Harada, … , Akira Mitani, Kohichi Tanaka
Takayuki Harada, … , Akira Mitani, Kohichi Tanaka
Published July 2, 2007
Citation Information: J Clin Invest. 2007;117(7):1763-1770. https://doi.org/10.1172/JCI30178.
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Research Article Ophthalmology Article has an altmetric score of 3

The potential role of glutamate transporters in the pathogenesis of normal tension glaucoma

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Abstract

Glaucoma, a progressive optic neuropathy due to retinal ganglion cell (RGC) degeneration, is one of the leading causes of irreversible blindness. Although glaucoma is often associated with elevated intraocular pressure (IOP), IOP elevation is not detected in a significant subset of glaucomas, such as normal tension glaucoma (NTG). Moreover, in some glaucoma patients, significant IOP reduction does not prevent progression of the disease. Thus, understanding IOP-independent mechanisms of RGC loss is important. Here, we show that mice deficient in the glutamate transporters GLAST or EAAC1 demonstrate spontaneous RGC and optic nerve degeneration without elevated IOP. In GLAST-deficient mice, the glutathione level in Müller glia was decreased; administration of glutamate receptor blocker prevented RGC loss. In EAAC1-deficient mice, RGCs were more vulnerable to oxidative stress. These findings suggest that glutamate transporters are necessary both to prevent excitotoxic retinal damage and to synthesize glutathione, a major cellular antioxidant and tripeptide of glutamate, cysteine, and glycine. We believe these mice are the first animal models of NTG that offer a powerful system for investigating mechanisms of neurodegeneration in NTG and developing therapies directed at IOP-independent mechanisms of RGC loss.

Authors

Takayuki Harada, Chikako Harada, Kazuaki Nakamura, Hun-Meng A. Quah, Akinori Okumura, Kazuhiko Namekata, Tadashiro Saeki, Makoto Aihara, Hiroshi Yoshida, Akira Mitani, Kohichi Tanaka

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 Total
Citations: 5 9 7 8 9 12 13 9 10 13 9 8 7 6 4 8 5 6 148
Citation information
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Citations to this article in year 2012 (6)

Title and authors Publication Year
Altered Phenotype of the Vestibular Organ in GLAST-1 Null Mice
SP Schraven, C Franz, L Rüttiger, H Löwenheim, A Lysakowski, W Stoffel, M Knipper
Journal of the Association for Research in Otolaryngology 2012
Animal Models of Glaucoma
RA Bouhenni, J Dunmire, A Sewell, DP Edward
Journal of Biomedicine and Biotechnology 2012
Dock3 stimulates axonal outgrowth via GSK-3β-mediated microtubule assembly
K Namekata, C Harada, X Guo, A Kimura, D Kittaka, H Watanabe, T Harada
The Journal of neuroscience : the official journal of the Society for Neuroscience 2012
A potential neuroprotective role of apolipoprotein E-containing lipoproteins through low density lipoprotein receptor-related protein 1 in normal tension glaucoma
H Hayashi, Y Eguchi, Y Fukuchi-Nakaishi, M Takeya, N Nakagata, K Tanaka, JE Vance, H Tanihara
The Journal of biological chemistry 2012
Group I mGluR-Mediated Inhibition of Kir Channels Contributes to Retinal Muller Cell Gliosis in a Rat Chronic Ocular Hypertension Model
M Ji, Y Miao, LD Dong, J Chen, XF Mo, SX Jiang, XH Sun, XL Yang, Z Wang
The Journal of neuroscience : the official journal of the Society for Neuroscience 2012
Therapeutic targets in the ASK1-dependent stress signaling pathways
HAYAKAWA R, HAYAKAWA T, TAKEDA K, ICHIJO H
Proceedings of the Japan Academy. Series B, Physical and biological sciences 2012

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