| ○種別 (必須): | □ | 学術論文 (審査論文)
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| ○言語 (必須): | □ | 英語
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| ○カテゴリ (推奨): |
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| ○著者 (必須): | 1. | (英) Semba K (日) (読)
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| 2. | (英) Namekata K (日) (読)
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| 3. | (英) Guo X (日) (読)
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| 4. | (英) Harada C (日) (読)
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| 5. | (英) Harada T (日) (読)
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| 6. | 三田村 佳典 ([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.外科系.眼科学])
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| ○題名 (必須): | □ | (英) Renin-angiotensin system regulates neurodegeneration in a mouse model of normal tension glaucoma. (日)
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| ○要約 (任意): | □ | (英) Glaucoma, one of the leading causes of irreversible blindness, is characterized by progressive degeneration of optic nerves and retinal ganglion cells (RGCs). In the mammalian retina, excitatory amino acid carrier 1 (EAAC1) is expressed in neural cells, including RGCs, and the loss of EAAC1 leads to RGC degeneration without elevated intraocular pressure (IOP). In the present study, we found that expressions of angiotensin II type 1 receptor (AT1-R) and Toll-like receptor 4 (TLR4) are increased in RGCs and retinal Müller glia in EAAC1-deficient (KO) mice. The orally active AT1-R antagonist candesartan suppressed TLR4 and lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) expressions in the EAAC1 KO mouse retina. Sequential in vivo retinal imaging and electrophysiological analysis revealed that treatment with candesartan was effective for RGC protection in EAAC1 KO mice without affecting IOP. In cultured Müller glia, candesartan suppressed LPS-induced iNOS production by inhibiting the TLR4-apoptosis signal-regulating kinase 1 pathway. These results suggest that the renin-angiotensin system is involved in the innate immune responses in both neural and glial cells, which accelerate neural cell death. Our findings raise intriguing possibilities for the management of glaucoma by utilizing widely prescribed drugs for the treatment of high blood pressure, in combination with conventional treatments to lower IOP. (日)
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| ○キーワード (推奨): |
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| ○誌名 (必須): | □ | Cell Death & Disease ([Nature Publishing Group])
(eISSN: 2041-4889)
| ○ISSN (任意): | □ | 2041-4889
ISSN: 2041-4889
(eISSN: 2041-4889) Title: Cell death & diseaseTitle(ISO): Cell Death DisPublisher: Springer Nature (NLM Catalog)
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(CrossRef)
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| ○巻 (必須): | □ | 5
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| ○号 (必須): |
| ○頁 (必須): | □ | e1333 e1333
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| ○都市 (任意): |
| ○年月日 (必須): | □ | 西暦 2014年 7月 17日 (平成 26年 7月 17日)
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| ○URL (任意): |
| ○DOI (任意): | □ | 10.1038/cddis.2014.296 (→Scopusで検索)
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| ○PMID (任意): | □ | 25032856 (→Scopusで検索)
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| ○備考 (任意): | 1. | (英) Article.ELocationID: 10.1038/cddis.2014.296 (日)
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| 2. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
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