Comprehensive genetic screening and establishment of novel therapeutic method in retinitis pigmentosa
Project/Area Number |
19K09929
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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 | Nagasaki University (2020-2021) Kyoto University (2019) |
Principal Investigator |
Oishi Akio 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (50572955)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | 網膜色素変性 / 遺伝子検査 / 遺伝型表現型解析 / 環境因子 / 分化誘導 / stop codon readthrough / 次世代シーケンサー / 遺伝子治療 |
Outline of Research at the Start |
網膜色素変性は遺伝性疾患であり、進行性の網膜障害を来す。本研究では研究代表者がこれまで行ってきた網羅的遺伝子診断の成果を軸とし、premature termination codonの変異を持つ患者から樹立した疾患特異iPS細胞を用いてstop codon readthroughによる治療法を開発することを第一の目的とする。さらに既報の遺伝子を網羅的に調べても原因遺伝子が特定できなかった症例から、家系解析および人工知能を用いて原因となる遺伝子の候補を絞り込み、動物実験で表現型を確認することで新規遺伝子の同定を目指す。
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Outline of Final Research Achievements |
We performed comprehensive genetic screening in Japanese patients with retinitis pigmentosa. We established iPS cells from patients harboring specific variants. We identified causative variants in 98 patients and confirmed that EYS is the major cause of retinitis pigmentosa in Japan. We also reported genotype and phenotype of patients with some specific genes including CYP4V2, PROM1, and PRPH2. We found that environmental factors such as tobacco and light exposure may affect retinal degeneration. We established a new method to generate photoreceptor like cells from iPS cells, which consists of induction of CRX and NEUROD1.
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Academic Significance and Societal Importance of the Research Achievements |
網膜色素変性には多くの原因遺伝子があり、その頻度には人種間での差も大きい。日本で特に多い遺伝子、およびバリアントを特定することは、今後治療法を考えるうえでより多くの方を対象と出来るようにするための基礎的な情報となる。また現時点で確立した治療方法のないこの疾患について、喫煙が網膜変性を進行させる可能性を示したことは、禁煙というすぐにでも実行可能な介入を勧める根拠となる。またiPS細胞から効率的に視細胞様の細胞を分化させる方法は今後iPS細胞を使った研究を行う上で広く応用可能な技術となる。
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Report
(4 results)
Research Products
(18 results)
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[Journal Article] Genotype and Long-term Clinical Course of Bietti Crystalline Dystrophy in Korean and Japanese Patients.2021
Author(s)
Murakami Y, Koyanagi Y, Fukushima M, Yoshimura M, Fujiwara K, Akiyama M, Momozawa Y, Ueno S, Terasaki H, Oishi A, Miyata M, Ikeda H, Tsujikawa A, Mizobuchi K, Hayashi T, Fujinami K, Tsunoda K, Park JY, Han J, Kim M, Lee CS, Kim SJ, Park TK, Joo K, Woo SJ, Ikeda Y, Sonoda KH.
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Journal Title
Ophthalmol Retina
Volume: -
Issue: 12
Pages: 1269-1279
DOI
Related Report
Peer Reviewed / 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
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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