Primate model to study drusen formation and development of therapeutics
Project/Area Number |
26293377
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Ophthalmology
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Research Institution | 独立行政法人国立病院機構(東京医療センター臨床研究センター) |
Principal Investigator |
IWATA Takeshi 独立行政法人国立病院機構(東京医療センター臨床研究センター), 分子細胞生物学研究部, 部長 (90374157)
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Co-Investigator(Kenkyū-buntansha) |
溝田 淳 帝京大学, 医学部, 教授 (10239262)
下澤 律浩 国立研究開発法人医薬基盤・健康・栄養研究所, 霊長類医科学研究センター, 研究員 (50300786)
|
Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2014: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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Keywords | 医歯薬学 / 外科系臨床医学 / 眼科学 / 眼性化学・分子生物学 / ドルーゼン / 眼生化学・分子生物学 |
Outline of Final Research Achievements |
Early onset cynomolgus macaque monkey with macular drusen was characterized to identify disease-causing mutation and pathological change at tissue and cellular level. The affected monkeys with dominant inheritance develop drusen at two years after birth. Whole genome and whole exome analysis were preformed to narrow the disease locus to a small region on chromosome 1. Three candidate genes were identified to cosegregate with macular drusen. The retinal pigment epithelial (RPE) cells in the fovea of affected monkeys were identified to lose the characteristic of the epithelial cells, Epithelial-Mesenchymal Transition-like phenomenon, leading to change of cell morphology, decreased of autophagy and phagocytosis activities. Complement inhibitors were administered to affected monkey to suppress formation of drusen. Potential inhibitors are being developed.
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Report
(4 results)
Research Products
(32 results)
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[Journal Article] CCT2 https://www-kofu.jsps.go.jp/kofu1/images/bt_add_small.gifMutations Evoke Leber Congenital Amaurosis due to Chaperone Complex Instability.2016
Author(s)
Minegishi Y, Sheng X, Yoshitake K, Sergeev Y, Iejima D, Shibagaki Y, Monma N, Ikeo K, Furuno M, Zhuang W, Liu Y, Rong W, Hattori A, Iwata T.
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Journal Title
Sci Rep
Volume: 6
Issue: 1
Pages: 33742-33742
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Novel RP1L1 variants and genotype-photoreceptor microstructural phenotype associations in cohort of Japanese patients with occult macular dystrophy.2016
Author(s)
Fujinami K, Kameya S, Kikuchi S, Ueno S, Kondo M, Hayashi T, Shinoda K, Machida S, Kuniyoshi K, Kawamura Y, Akahori M, Yoshitake K, Katagiri S, Nakanishi A, Sakuramoto H, Ozawa Y, Tsubota K, Yamaki K, Mizota A, Terasaki H, Miyake Y, Iwata T, Tsunoda K.
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Journal Title
Invest Ophthalmol Vis Sci.
Volume: 57
Issue: 11
Pages: 4837-4846
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Identification of novel mutations in the LRR-cap domain of C21orf2 in Japanese patients with retinitis pigmentosa and cone-rod dystrophy.2016
Author(s)
Suga A, Mizota A, Kato M, Kuniyoshi K, Yoshitake K, Sultan W, Yamazaki M, Shimomura Y, Ikeo K, Tsunoda K, Iwata T.
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Journal Title
Invest Ophthalmol Vis Sci
Volume: 57
Issue: 10
Pages: 4255-4263
DOI
Related Report
Peer Reviewed
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[Journal Article] Electroretinographic evaluations of retinal function before, just after, and after intravitreal injections.2016
Author(s)
Yagura K, Shinoda K, Matsumoto S, Terauchi G, Kawashima M, Watanabe E, Matsumoto H, Iwata T, Mizota A, Miyake Y.
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Journal Title
Sci Rep
Volume: 6
Issue: 1
Pages: 31104-31104
DOI
Related Report
Peer Reviewed
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[Journal Article] Clinical and genetic findings of autosomal recessive bestrophinopathy in Japanese cohort.2016
Author(s)
Nakanishi A, Ueno S, Hayashi T, Katagiri S, Kominami T, Ito Y, Gekka T, Masuda Y, Tsuneoka H, Shinoda K, Hirakata A, Inoue M, Fujinami K, Tsunoda K, Iwata T, Terasaki H.
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Journal Title
Am J Ophthalmol.
Volume: 168
Pages: 86-94
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Novel mutations in the gene for α-subunit of retinal cone cyclic nucleotide-gated channels in a Japanese patient with congenital achromatopsia.2016
Author(s)
Kuniyoshi K, Muraki-Oda S, Ueyama H, Toyoda F, Sakuramoto H, Ogita H, Irifune M, Yamamoto S, Nakao A, Tsunoda K, Iwata T, Ohji M, Shimomura Y.
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Journal Title
Jpn J Ophthalmol
Volume: 60
Issue: 3
Pages: 187-197
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Congenital Achromatopsia and Macular Atrophy Caused by a Novel Recessive PDE6C Mutation (p.E591K).2015
Author(s)
Katagiri S, Hayashi T, Yoshitake K, Sergeev Y, Akahori M, Furuno M, Nishino J, Ikeo K, Tsunoda K, Tsuneoka H, Iwata T.
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Journal Title
Ophthalmic Genet.
Volume: Jun;36(2)
Issue: 2
Pages: 137-44
DOI
Related Report
Peer Reviewed
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[Journal Article] RHO mutations (p.W126L and p.A346P) in two Japanese families with autosomal dominant retinitis pigmentosa2014
Author(s)
Katagiri S, Hayashi T, Akahori M, Itabashi T, Nishio J, Yoshitake K, Furuno M, Ikeo K, Okada T, Tsuneoka H, Iwata T
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Journal Title
J Ophthalmol
Volume: 2014
Pages: 210947-210947
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Whole exome analysis identifies frequent CNGA1 mutations in Japanese population with autosomal recessive retinitis pigmentosa2014
Author(s)
Katagiri S, Akahori M, Sergeev Y, Yoshitake K, Ikeo K, Furuno M, Hayashi T, Kondo M, Ueno S, Tsunoda K, Shinoda K, Kuniyoshi K, Tsurusaki Y, Matsumoto N, Tsuneoka H, Iwata T.
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Journal Title
Plos One
Volume: 9(9)
Issue: 9
Pages: e108721-e108721
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Novel C8orf37 mutations in patients with early-onset retinal dystrophy, macular atrophy, cataracts, and high myopia.2014
Author(s)
Katagiri S, Hayashi T, Yoshitake K, Akahori M, Ikeo K, Gekka T, Tsuneoka H, Iwata T.
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Journal Title
Ophthalmic Genetics
Volume: 12
Pages: 1-8
Related Report
Peer Reviewed
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