| Project/Area Number |
12307037
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | Osaka University |
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Principal Investigator |
TANO Yasuo Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (80093433)
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| Co-Investigator(Kenkyū-buntansha) |
KAMEI Motohiro Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40281125)
YAMAMOTO Shuji Osaka University Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (80294065)
FUJIKADO Takashi Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (50243233)
MORIMURA Hiroyuki Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (70314325)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥42,170,000 (Direct Cost: ¥38,600,000、Indirect Cost: ¥3,570,000)
Fiscal Year 2002: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2001: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2000: ¥26,700,000 (Direct Cost: ¥26,700,000)
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| Keywords | Age-related macular degeneration / Degenerative myopia / Starsrardt Disease / Retinitis Pigmentosa / ABCA4 gene / Tissue Inhibitor of Metalloproteinase-3 (TIMP-3) / Macular translocation / NO / 難治性黄斑疾患 / SAGE法 / RGR遺伝子 / 黄斑部ライブラリー / 遺伝子発現解析 / 高度視力障害 / 原因遺伝子検索 / 脈絡膜新生血管 / 遺伝子治療 / HVJ(仙台ウイルス)-liposome / Tissue inhibitor of metalloproteinase-3(TIMP-3) |
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| Research Abstract |
The final goal of this project is revealing the pathogenesis and developing the treatment to the complicated macular diseases that are the leading cause of severe visual impairment and have no established treatment. During this study period, we attempted to identify the causal gene mutations in hereditary retinal diseases, analyze those genes functions and relations between mutations and phenotypes, investigate the pathogenesis of age-related macular degeneration and degenerative myopia, and develop treatments for neovascular maculopathy associated with those diseases.
We obtained the following rcsults:
1) gene mutations in hereditary retinal diseases and relations between mutations and phenotypes : We identified point mutations in the XLRSI Gene in retinitis pigmentosa and mutations in the 11-cis Retinol Dehydrogenase Gene in patients with Fundus Albipunctatus. We also found ABCA4 gene mutations in Japanese patients with Stargardt Disease and Retinitis Pigmentosa. Furthermore, we discov
… More
ered by tracking the history of the patients that all Retinitis Pigmentosa with ABCA4 gene mutations showed Stargardt Disease like fundus changes in the early stage of the disease and atypical cases that were difficult to be distinguished from Corn-rod dystrophy. We suspect that Retinitis Pigmentosa and Corn-rod dystrophy with ABCA4 gene mutations may be the advanced stage of Stargardt Disease.
2) Age-related macular degeneration : To suppress choroidal neovaseularization associated with age-related macular degeneration, we demonstrated that experimental choroidal neovaseularization is inhibited by overexpression of tissue inhibitor of metalloproteinases-3 (TIMP-3) in retinal pigment epithelium cells. As the treatment for age-related macular degeneration, we clinically performed macular translocation surgery. We histologicaly evaluated the retinal changes after retinal translocation surgery with scleral imbrication in dog eyes and found the retinal damages in the part of retinal foldings. To avoid those complications, we modified the surgery and developed macular translocation with chorioscleral outfolding. We also evaluated the surgical outcomes and found that reading ability improved after macular translocation surgery with 360-degree retinotomy.
3) Pathogenesis of degenerative myopia: We searched factors contributing the pathogenesis of myopia in an animal model of myopia, and demonstrated that inhibition of nitric oxide synthase can suppress lens-induced myopia. Less
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