サエキ タダシロウ
  佐伯 忠賜朗
   所属   医学部 医学科(東京女子医科大学病院)
   職種   講師
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 The potential role of glutamate transporters in the pathogenesis of normal tension glaucoma.
掲載誌名 正式名:The Journal of clinical investigation
略  称:J Clin Invest
ISSNコード:(0021-9738)0021-9738(Linking)
掲載区分国外
巻・号・頁 117(7),1763-70頁
著者・共著者 Harada Takayuki, Harada Chikako, Nakamura Kazuaki, Quah Hun-Meng A, Okumura Akinori, Namekata Kazuhiko, Saeki Tadashiro, Aihara Makoto, Yoshida Hiroshi, Mitani Akira, Tanaka Kohichi
発行年月 2007/07
概要 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.
DOI 10.1172/JCI30178
PMID 17607354