Development of retinal disease regulation from prevention to therapeutic technology targeting hypoxia responses
Project/Area Number |
18K09424
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 56060:Ophthalmology-related
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Research Institution | Keio University |
Principal Investigator |
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
Keywords | 網膜 / 低酸素 / 血管新生 / 神経変性 / 外科 / 発生・分化 / トランスレーショナルリサ ーチ |
Outline of Final Research Achievements |
We aimed to establish anti-HIF therapies in order to prevent various ocular diseases and systemic malfunction. We have reported the therapeutic effect of a known HIF inhibitor topotecan in murine oxygen-induced retinopathy and ischemic reperfusion models. Furthermore, novel HIF inhibitors including halofuginone, hydroxycitric acid, lactoferrin, fish ingredients, vitamin B6, and fenofibrate have been screened. We have reported their therapeutic effects verified with various animal models. In addition, we have reported functions of a non-visual photoreceptor OPN5 in myopia progression inspired by the report of hypoxia response playing a role in myopia by another research group abroad.
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Academic Significance and Societal Importance of the Research Achievements |
研究開始前までに得られた異常な低酸素応答による網膜での病態形成知見を基に、食物由来因子ライブラリを用いた新たなスクリーニングを実施し、新規HIF阻害物質の同定ならびに、その治療効果を様々な動物モデルで検証した。本研究で得られた候補物質はいずれも日常的に摂取可能な機能性食品やサプリメントとして活用できる可能性があり、加齢黄斑変性のみならず糖尿病網膜症などの他の血管新生網膜疾患の治療、個体そのものの機能低下に対して、安全に介入できる可能性を見出した。また近視進行抑制の機序に関しても本研究を基に明らかとし、今後多くの臨床的な応用が期待できる成果を得た。
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Report
(4 results)
Research Products
(201 results)
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[Journal Article] Long-term follow-up of a Chinese patient with KCNV2-retinopathy2021
Author(s)
Lie H, Wang G, Liu X, Meng X, Long Y, Ren J, Yang L, Fujinami-Yokokawa Y, Kurihara T, Tsubota K, Fujinami K, Li S.
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Journal Title
Ophthalmic Genet
Volume: 42(2)
Issue: 2
Pages: 144-149
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] RP2-associated retinal disorder in a Japanese cohort: Report of novel variants and a literature review, identifying a genotype-phenotype association.2020
Author(s)
Fujinami K, Liu X, Ueno S, Mizota A, Shinoda K, Kuniyoshi K, Fujinami-Yokokawa Y, Yang L, Arno G, Pontikos N, Kameya S, Kominami T, Terasaki H, Sakuramoto H, Nakamura N, Kurihara T, Tsubota K, Miyake Y, Yoshiake K, Iwata T, Tsunoda K; Japan Eye Genetics Consortium Study Group.
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Journal Title
Am J Med Genet C Semin Med Genet.
Volume: 184
Issue: 3
Pages: 675-693
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Clinical and genetic characteristics of Stargardt disease in a large Western China cohort: Report 12020
Author(s)
Liu X, Meng X, Yang L, Long Y, Fujinami-Yokokawa Y, Ren J, Kurihara T, Tsubota K, Tsunoda K, Fujinami K, Li S; East Asia Inherited Retinal Disease Society Study Group.
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Journal Title
Am J Med Genet C Semin Med Genet
Volume: 184(3)
Issue: 3
Pages: 694-707
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Clinical and Genetic Characteristics of 15 Affected Patients From 12 Japanese Families with GUCY2D-Associated Retinal Disorder2020
Author(s)
Liu X, Fujinami K, Kuniyoshi K, Kondo M, Ueno S, Hayashi T, Mochizuki K, Kameya S, Yang L, Fujinami-Yokokawa Y, Arno G, Pontikos N, Sakuramoto H, Kominami T, Terasaki H, Katagiri S, Mizobuchi K, Nakamura N, Yoshitake K, Miyake Y, Li S, Kurihara T, Tsubota K, Iwata T, Tsunoda K; Japan Eye Genetics Consortium
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Journal Title
Transl Vis Sci Technol
Volume: 11
Issue: 6
Pages: 2-2
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Clinical and genetic characteristics of 10 Japanese patients with PROM1-associated retinal disorder: A report of the phenotype spectrum and a literature review in the Japanese population.2020
Author(s)
Fujinami K, Oishi A, Yang L, Arno G, Pontikos N, Yoshitake K, Fujinami-Yokokawa Y, Liu X, Hayashi T, Katagiri S, Mizobuchi K, Mizota A, Shinoda K, Nakamura N, Kurihara T, Tsubota K, Miyake Y, Iwata T, Tsujikawa A, Tsunoda K; Japan Eye Genetics Consortium study group.
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Journal Title
Am J Med Genet C Semin Med Genet.
Volume: 184
Issue: 3
Pages: 656-674
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Spatial Functional Characteristics of East Asian Patients With Occult Macular Dystrophy (Miyake disease)2020
Author(s)
Yang L, Joo K, Tsunoda K, Kondo M, Fujinami-Yokokawa Y, Arno G, Pontikos N, Liu X, Nakamura N, Kurihara T, Tsubota K, Iwata T, Li H, Zou X, Wu S, Sun Z, Ahn SJ, Kim MS, Mun YS, Park KH, Robson AG, Miyake Y, Woo SJ, Sui R, Fujinami K
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Journal Title
Am J Ophthalmol
Volume: 221
Pages: 169-180
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinical and Genetic Characteristics of 18 Patients from 13 Japanese Families with CRX-associated retinal disorder: Identification of Genotype-phenotype Association2020
Author(s)
Fujinami-Yokokawa Y, Fujinami K, Kuniyoshi K, Hayashi T, Ueno S, Mizota A, Shinoda K, Arno G, Pontikos N, Yang L, Liu X, Sakuramoto H, Katagiri S, Mizobuchi K, Kominami T, Terasaki H, Nakamura N, Kameya S, Yoshitake K, Miyake Y, Kurihara T, Tsubota K, Miyata H, Iwata T, Tsunoda K; Japan Eye Genetics Consortium.
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Journal Title
Sci Rep
Volume: 12
Issue: 1
Pages: 9531-9531
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Genetic Spectrum of EYS-associated Retinal Disease in a Large Japanese Cohort: Identification of Disease-associated Variants with Relatively High Allele Frequency.2020
Author(s)
Yang L, Fujinami K, Ueno S, Kuniyoshi K, Hayashi T, Kondo M, Mizota A, Naoi N, Shinoda K, Kameya S, Fujinami-Yokokawa Y, Liu X, Arno G, Pontikos N, Kominami T, Terasaki H, Sakuramoto H, Katagiri S, Mizobuchi K, Nakamura N, Mawatari G, Kurihara T, Tsubota K, Miyake Y, Yoshitake K, Iwata T, Tsunoda K; JEGC study group.
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Journal Title
Sci Rep.
Volume: 10
Issue: 1
Pages: 1-10
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Relationship between nerve fiber layer defect and the presence of epiretinal membrane in a Japanese population: The JPHC-NEXT Eye Study.2020
Author(s)
Uchida A, Sasaki M, Motomura K, Yuki K, Kurihara T, Tomita Y, Ozawa Y, Yamagishi K, Kawasaki R, Hanyuda A, Sawada N, Tsubota K, Tsugane S, Iso H.
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Journal Title
Sci Rep
Volume: 10
Issue: 1
Pages: 779-779
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] High Myopia and Its Associated Factors in JPHC-NEXT Eye Study: A Cross-Sectional Observational Study.2019
Author(s)
Mori K, Kurihara T, Uchino M, Torii H, Kawashima M, Sasaki M, Ozawa Y, Yamagishi K, Iso H, Sawada N, Tsugane S, Yuki K, Tsubota K.
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Journal Title
J Cli Med
Volume: 8
Issue: 11
Pages: 1788-1788
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Current Prevalence of Myopia and Association of Myopia With Environmental Factors Among Schoolchildren in Japan.2019
Author(s)
Erisa Yotsukura, Hidemasa Torii, Mikako Inokuchi, Mitsuaki Tokumura, Miki Uchino, Kyosei Nakamura, Mari Hyodo, Kiwako Mori, Xiaoyan Jiang, Shin-ichi Ikeda, Shinichiro Kondo, Kazuno Negishi, Toshihide Kurihara, Kazuo Tsubota
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Journal Title
JAMA Ophthalmology
Volume: 137(11)
Issue: 11
Pages: 1233-1239
DOI
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Peer Reviewed / Open Access
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[Presentation] 黄斑円孔に対する硝子体手術における内境界膜剥離の術後視野障害への影響2020
Author(s)
秋野邦彦, 渡邊一弘, 篠田肇, 永井紀博, 栗原俊英, 内田敦郎, 伴紀充, 堀内直樹, 園部秀樹, 坪田一男, 小沢洋子
Organizer
第59回日本網膜硝子体学会総会
Related Report
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[Presentation] 近視性脈絡膜新生血管に対する抗VEGF療法の視力予後に関する因子の検討2019
Author(s)
虫賀庸朗, 永井紀博, 鈴木美砂, 南早紀子, 栗原俊英, 園部秀樹, 秋野邦彦, 渡邊一弘, 内田敦郎, 篠田肇, 坪田一男, 小沢洋子
Organizer
第58回日本網膜硝子体学会総会
Related Report
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[Presentation] 加齢黄斑変性における眼軸長と脈絡膜厚の関連の解析2019
Author(s)
佐藤真帆, 永井紀博, 鈴木美砂, 南早紀子, 栗原俊英, 園部秀樹, 秋野邦彦, 渡邊一弘, 内田敦郎, 篠田肇, 坪田一男, 小沢洋子
Organizer
第58回日本網膜硝子体学会総会
Related Report
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[Presentation] 黄斑上膜に対する硝子体手術の術後に視野障害が出現した症例の6か月経過2019
Author(s)
渡邊一弘, 栗原智樹, 篠田肇, 結城賢弥, 永井紀博, 栗原俊英, 内田敦郎, 伴紀充, 園部秀樹, 秋野邦彦, 坪田一男, 小沢洋子
Organizer
第58回日本網膜硝子体学会総会
Related Report
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[Presentation] Myopia crisis among school children in Tokyo2019
Author(s)
Erisa Yotsukura, Hidemasa Torii, Mikako Inokuchi, Mitsuaki Tokumura, Miki Uchino, Kiwako Mori, Xiaoyan Jiang, Shin-ichi Ikeda, Shinichiro Kondo, Kazuno Negishi, Toshihide Kurihara, Kazuo Tsubota
Organizer
The 17th International Myopia Conferenc
Related Report
Int'l Joint Research
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[Presentation] 網膜中DHA含有リン脂質の視覚機能に及ぼす影響と生理学的意義の解明2019
Author(s)
黒羽小羊子, 堅田侑作, 宍倉匡介, 三輪幸裕, 坪田一男, 栗原俊英, 有田誠
Organizer
黒羽小羊子, 堅田侑作, 宍倉匡介, 三輪幸裕, 坪田一男, 栗原俊英, 有田誠
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[Presentation] ブラジル赤道部付近における学童の 1 年間の屈折値変化量と眼軸長変化量2019
Author(s)
四倉絵里沙, 鳥居秀成, 内野美樹, 白石哲郎, 岡直幸, 森紀和子, 姜效炎, 池田真一, 栗原俊英, 根岸一乃, 坪田一男
Organizer
第123回日本眼科学会総会
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[Presentation] バイオレットライトを使用した前向き研究における成人強度近視 2 症例の眼軸長伸長量2019
Author(s)
鳥居秀成, 戸田郁子, 大野綾香, 近藤眞一郎, 四倉絵里沙, 森紀和子, 小橋英長, 姜效炎, 池田真一, 栗原俊英, 坪田一男
Organizer
第123回日本眼科学会総会
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[Presentation] 白内障手術患者を対象とした血漿-房水グルコース濃度相関の血糖変動状態による変化2019
Author(s)
栗原俊英, 有田陽子, 日高悠葵, 西恭代, 常吉由佳里, 鳥居秀成, 木下卓, 西崎早織, 白川佳則, 木村 翔, 坪田一男, 根岸一乃
Organizer
第123回日本眼科学会総会
Related Report
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[Presentation] Distribution of generalized functional phenotype of East Asian Patients with Stargardt Disease (STGD1): EAStar studies report 22018
Author(s)
Xiao Liu, Lizhu Yang, Kwangsic Joo, Kazushige Tsunoda, Takaaki Hayashi, Kei Shinoda, Atsushi Mizota, Mineo Kondo, Kazuki Kuniyoshi, Yu (Yokokawa) Fujinami, Gavin Arno, Toshihide Kurihara, Kazuo Tsubota, Yozo Miyake, Ya Li, Kyu Hyung Park, Dae Joong Ma, Hyeong Gon Yu, Bo Lei, Takeshi Iwata, Se Joon Woo
Organizer
56th ISCEV Symposium
Related Report
Int'l Joint Research
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[Presentation] Genotype Phenotype Association in East Asian Patients with Occult Macular Dystrophy (Miyake’s disease); EAOMD Report No.42018
Author(s)
Yu (Yokokawa) Fujinami, Lizhu Yang, Kwangsic Joo, Kazushige Tsunoda, Mineo Kondo, Gavin Arno, Xiao Liu, Toshihide Kurihara, Kazuo Tsubota, Xuan Zou, Hui Li, Kyu Hyung Park, Yozo Miyake, Takeshi Iwata, Se Joon Woo, Ruifang Sui, Kaoru Fujinami
Organizer
56th ISCEV Symposium
Related Report
Int'l Joint Research
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[Presentation] WITHDRAWN - Incidence, Risk Factors, and Treatment of Retinopathy of Prematurity In Low-Birthweight Infants2018
Author(s)
Tomoki Kurihara, Toshihide Kurihara, Norihiro Nagai, Mamoru Kamoshita, Yuki Hidaka, Hideki Sonobe, Hajime Shinoda, Kazuo Tsubota, Yoko Ozawa
Organizer
ARVO 2018 Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] Multimodal imaging of East Asian Patients with Occult Macular Dystrophy (Miyake’s disease): EAOMD Report No. 32018
Author(s)
Kwangsic Joo, Lizhu Yang, Kazushige Tsunoda, Mineo Kondo, Yu Fujinami, Gavin Arno, Toshihide Kurihara, Kazuo Tsubota, Takeshi Iwata, Xuan Zou, Hui Li, Yozo Miyake, Kyu Hyung Park, Kaoru Fujinami, Ruifang Sui, Se Joon Woo
Organizer
ARVO 2018 Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] Clinical and Genetic Characteristics of East Asian Patients with Occult Macular Dystrophy (Miyake’s disease); EAOMD Report No.12018
Author(s)
Kaoru Fujinami, Lizhu Yang, Kwangsic Joo, Kazushige Tsunoda, Yuichi Kawamura, Yu Fujinami, Gavin Arno, Toshihide Kurihara, Kazuo Tsubota, Xuan Zou, Hui Li, Kyu Hyung Park, Takeshi Iwata, Yozo Miyake, Se Joon Woo, Ruifang Sui
Organizer
ARVO 2018 Annual Meeting
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Int'l Joint Research
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[Presentation] Predictive factors for better short-term outcome in idiopathic epiretinal membrane after pars plana vitrectomy2018
Author(s)
Sakiko Minami, Yuta Shigeno, Hajime Shinoda, Norihiro Nagai, Toshihide Kurihara, Mamoru Kamoshita, Kazuhiro Watanabe, Hideki Sonobe, Yuki Hidaka, Kazuo Tsubota, Yoko Ozawa
Organizer
ARVO 2018 Annual Meeting
Related Report
Int'l Joint Research
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[Book] 眼科2021
Author(s)
栗原俊英
Total Pages
100
Publisher
金原出版株式会社
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