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著者 |
Matsuo, Toshihiko
Department of Ophthalmology, Okayama University Hospital
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Liu, Shihui
Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems
Uchida, Tetsuya
Polymer Materials Science, Okayama University Graduate School of Natural Science and Technology
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Onoue, Satomi
Laboratory of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka
Nakagawa, Shinsaku
Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University
Ishii, Mayumi
Drug Discovery Initiative, The University of Tokyo
Kanamitsu, Kayoko
Drug Discovery Initiative, The University of Tokyo
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抄録 | NK-5962 is a key component of photoelectric dye-based retinal prosthesis (OUReP). In testing the safety and efficacy, NK-5962 was safe in all tests for the biological evaluation of medical devices (ISO 10993) and effective in preventing retinal cells from death even under dark conditions. The long-term implantation of the photoelectric dye-coupled polyethylene film in the subretinal space of hereditary retinal dystrophic (RCS) rats prevented neurons from apoptosis in the adjacent retinal tissue. The intravitreous injection of NK-5962 in the eyes of RCS rats, indeed, reduced the number of apoptotic cells in the retinal outer nuclear layer irrespective of light or dark conditions. In this study, we reviewed the in vitro and in vivo evidence of neuroprotective effect of NK-5962 and designed pharmacokinetic experiments. The in vitro IC50 of 1.7 μM, based on the protective effect on retinal cells in culture, could explain the in vivo EC50 of 3 μM that is calculated from concentrations of intravitreous injection to prevent retinal neurons from apoptosis. Pharmacokinetics of NK-5962 showed that intravenous administration, but not oral administration, led to the effective concentration in the eye of rats. NK-5962 would be a candidate drug for delaying the deterioration of retinal dystrophy, such as retinitis pigmentosa.
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キーワード | NK-5962
photoelectric dye
apoptosis
retinal neuron
neuroprotection
pharmacokinetics
ADME
phototoxic/photosensitive assay
reactive oxygen species assay
photosafety
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発行日 | 2021-6-21
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出版物タイトル |
Life
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巻 | 11巻
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号 | 6号
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出版者 | MDPI
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開始ページ | 591
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ISSN | 2075-1729
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © 2021 by the authors
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論文のバージョン | publisher
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DOI | |
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関連URL | isVersionOf https://doi.org/10.3390/life11060591
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ライセンス | https://creativecommons.org/licenses/by/4.0/
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