2020 Fiscal Year Annual Research Report
Development of retinal disease regulation from prevention to therapeutic technology targeting hypoxia responses
| Project/Area Number |
18K09424
|
|---|
| Research Institution | Keio University |
|---|
Principal Investigator |
栗原 俊英 慶應義塾大学, 医学部(信濃町), 講師 (50365342)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Keywords | 網膜 / 低酸素 / 血管新生 / 神経変性 |
|---|
| Outline of Annual Research Achievements |
申請者はこれまで、網膜局所における低酸素誘導因子（hypoxia-inducible factor; HIF）を中心とする異常な低酸素応答が、複雑で他因子疾患である加齢黄斑変性の病態形成に重要な役割を果たしていることを見出した。そこで、本研究課題では、個体の低酸素応答変化の解析、加齢関連疾患の低酸素応答制御による抑制効果の検討、HIF阻害剤投与による加齢関連疾患制御技術の創出を試みる。これまでにin vitroハイスループット・スクリーニング系を構築し、天然物から合成化合物、ドラッグリポジショニングのライブラリに至るまで、いくつかのHIF阻害効果を有する化合物を得ることができている。また本研究課題実施にあたり、様々な動物モデルに対する既知・新規のHIF阻害剤による表現型への介入を行ってきた。
当初の計画通り低酸素応答を標的とした網膜疾患制御技術開発がさらに確立された。研究期間内に、既知のHIF阻害剤トポテカンを用いて、網膜血管新生の評価系であるマウス酸素誘導網膜症（OIR）モデル(Miwa Y, Kurihara T, et al. Neurochem Int. 2019)、および網膜神経節細胞死の評価系である網膜虚血再灌流(I/R)モデル(Kunimi H, Kurihara T, et al. PeerJ. 2019)で得られた治療効果を報告した。さらに新規HIF阻害剤スクリーニングで得られたハロフジノン(Kunimi H, Miwa Y, Kurihara T, et al. Int J Mol Sci. 2019)、ヒドロキシクエン酸(Ibuki M, Kurihara T, et al. Int J Mol Sci. 2019)、ラクトフェリン(Ibuki M, Kurihara T, et al. Front Pharmacol. 2020)および魚類抽出物(Shoda C, Kurihara T, et al. Nutrients. 2020)、ビタミンB6 (Ibuki M, Kurihara T, et al. Int J Mol Sci. 2020)、フェノフィブラート(Lee D, Kurihara T, et al. Pharmaceuticals. 2021)の様々な動物モデルにおける治療効果を報告した。
|
-
-
[Journal Article] Efficacy and safety of 0.01% atropine for prevention of childhood myopia in a 2-year randomized placebo-controlled study2021
Author(s)
Hieda O, Hiraoka T, Fujikado T, Ishiko S, Hasebe S, Torii H, Takahashi H, Nakamura Y, Sotozono C, Oshika T, Morimoto T, Nishida K, Nishikawa N, Song YS, okutake T, Nishi Y, Shigeno Y, Kurihara T, Negishi K, Tsubota K, Ono M, Nakai T, Tan D, Tanaka S, Kinoshita S
-
Journal Title
Jpn J Ophthalmol
Volume: -
Pages: -
DOI
Peer Reviewed / Open Access
-
[Journal Article] Axial Length and Prevalence of Myopia among Schoolchildren in the Equatorial Region of Brazi2020
Author(s)
Yotsukura E, Torii H, Ozawa H, Hida RY, Shiraishi T, Corso Teixeira I, Rautha YVBL, Moraes do Nascimento CF, Mori K, Uchino M, Kurihara T, Negishi K, Tsubota K
-
Journal Title
J Clin Med
Volume: 10
Pages: 115-115
DOI
Peer Reviewed / Open Access
-
[Journal Article] Long-term follow-up of a Chinese patient with <i>KCNV2</i>-retinopathy2020
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
-
Journal Title
Ophthalmic Genet
Volume: 42
Pages: 144-149
DOI
Peer Reviewed / Open Access
-
-
-
-
-
-
-
[Journal Article] Association between axial length and choroidal thickness in early age-related macular degeneration2020
Author(s)
Sato M, Minami S, Nagai N, Suzuki M, Kurihara T, Shinojima A, Sonobe H, Akino K, Ban N, Watanabe K, Uchida A, Shinoda H, Tsubota K, Ozawa Y
-
Journal Title
PLoS One
Volume: 15
Pages: -
DOI
Peer Reviewed / Open Access
-
-
-
[Journal Article] RP2-associated retinal disorder in a Japanese cohort: Report of novel variants and a literature review, identifying a genotype-phenotype association2020
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
-
Journal Title
Am J Med Genet C Semin Med Genet
Volume: 184
Pages: 675-693
DOI
Peer Reviewed / Open Access
-
-
[Journal Article] Clinical and genetic characteristics of Stargardt disease in a large Western China cohort2020
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
-
Journal Title
Am J Med Genet C Semin Med Genet
Volume: 184
Pages: 694-707
DOI
Peer Reviewed / Open Access
-
-
[Journal Article] Clinical and Genetic Characteristics of 15 Affected Patients From 12 apanese Families with <i>GUCY2D</i>-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
-
Journal Title
Transl Vis Sci Technol
Volume: 9
Pages: 2-2
DOI
Peer Reviewed / Open Access
-
[Journal Article] Japan Eye Genetics Consortium study group. 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 population2020
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
-
Journal Title
Am J Med Genet C Semin Med Genet
Volume: 184
Pages: 656-674
DOI
Peer Reviewed / Open Access
-
[Journal Article] Hyperreflective Material in Optical Coherence Tomography Images of Eyes with Myopic Choroidal Neovascularization May Affect the Visual Outcome2020
Author(s)
Mushiga Y, Minami S, Uchida A, Nagai N, Suzuki M, Kurihara T, Sonobe H, Ban N, Watanabe K, Shinoda H, Tsubota K, Ozawa Y
-
Journal Title
J Clin Med
Volume: 9
Pages: 2394-2394
DOI
Peer Reviewed / Open Access
-
[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
-
Journal Title
Am J Ophthalmol
Volume: 221
Pages: 169-180
DOI
Peer Reviewed / Open Access
-
[Journal Article] Clinical and Genetic Characteristics of 18 Patients from 13 Japanese Families with CRX-associated retinal disorder2020
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
-
Journal Title
Sci Rep
Volume: 12
Pages: 9531-9531
DOI
Peer Reviewed / Open Access
-
-
[Journal Article] Macular Pigment Optical Density and Photoreceptor Outer Segment Length as Predisease Biomarkers for Age-Related Macular Degeneration2020
Author(s)
Nagai N, Minami S, Suzuki M, Shinoda H, Kurihara T, Sonobe H, Watanabe K, Uchida A, Ban N, Tsubota K, Ozawa Y
-
Journal Title
J Clin Med
Volume: 9
Pages: 1347-1347
DOI
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
[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
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
