Development of novel comprehensive molecular therapies for intraocular proliferative diseases targeting periretinal fibrovascular membranes
| Project/Area Number |
26293374
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | Kyushu University |
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Principal Investigator |
Yoshida Shigeo 九州大学, 医学(系)研究科(研究院), 准教授 (50363370)
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| Co-Investigator(Kenkyū-buntansha) |
石橋 達朗 九州大学, 大学病院, その他 (30150428)
中尾 新太郎 九州大学, 大学病院, 助教 (50583027)
佐々 由季生 福岡大学, 医学部, 講師 (80580315)
池田 康博 九州大学, 医学(系)研究科(研究院), 准教授 (20380389)
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| 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: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2015: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
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| Keywords | 糖尿病網膜症 / 加齢黄斑変性 / ペリオスチン / テネイシンC / 眼内増殖 / 分子標的薬 / 核酸医薬 / 薬物送達 / 網脈絡膜増殖 / 脈絡膜増殖組織 |
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| Outline of Final Research Achievements |
In intraocular proliferative diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD), fibro (vascular) membrane (FVM) formation above and beneath the retina plays a pivotal role in the primary pathology. We have succeeded in extracting approximately 100 highly expressed genes in FVMs associated with PDR, which included periostin and tenascin-C, a matricellular protein.
We showed that the expression of periostin and tenascin-C was increased in the retinas of a mouse model of oxygen-induced retinal neovascularization (NV) and in choroidal NV. A new class of RNA interference (RNAi) agent that targets periostin and tenascin-C had a significant inhibitory effect on the retinal NV, CNV and choroidal fibrosis than control RNAi with no apparent adverse effects. These findings suggest a causal relationship between these matricellular proteins and intraocular FVM formation, and a potential therapeutic role of the new intravitreal RNAi agents for DR and AMD.
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] M2 Macrophages Enhance Pathological Neovascularization in the Mouse Model of Oxygen-Induced Retinopathy2015
Author(s)
1Zhou Y, Yoshida S, Nakao S, Yoshimura T, Kobayashi Y, Nakama T, Kubo Y, Miyawaki K, Yamaguchi M, Ishikawa K, Oshima Y, Akashi K,Ishibashi T
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Journal Title
Invest Ophthalmol Vis Sci.
Volume: 56
Issue: 8
Pages: 4767-77
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Inhibition of choroidal fibrovascular membrane formation by new class of RNA interference therapeutic agent targeting periostin.2015
Author(s)
Nakama T, Yoshida S, Ishikawa K, Kobayashi Y, Zhou Y, Nakao S, Sassa Y, Oshima Y, Takao K, Shimahara A, Yoshikawa K, Hamasaki T, Ohgi T, Hayashi H, Matsuda A, Kudo A, Nozaki M, Ogura Y, Kuroda M, Ishibashi T.
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Journal Title
Gene Therapy.
Volume: 22
Issue: 2
Pages: 127-137
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Microarray analysis of gene expression in fibrovascular membranes excised from patients with proliferative diabetic retinopathy.2015
Author(s)
Ishikawa K, Yoshida S, Kobayashi Y, Zhou Y, Nakama T, Nakao S, Sassa Y, Oshima Y, Niiro H, Akashi K, Kono T, Ishibashi T.
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Journal Title
Investigative Ophthalmology and Visual Science.
Volume: 56
Issue: 2
Pages: 932-946
DOI
Related Report
Peer Reviewed
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