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Molecular biological investigation of complicated macular diseases

Research Project

Project/Area Number 12307037
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionOsaka University

Principal Investigator

TANO Yasuo  Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (80093433)

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)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
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)
KeywordsAge-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)
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

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Takahashi T, et al.: "Inhibition of experimental choroidal neovascularization by overexpression of tissue inhibitor of metalloproteinases-3 in retinal pigment epithelium cells"American Journal of Ophthalmology. 130. 774-781 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujikado T, et al.: "Effect of a Nitric Oxide Synthase Inhibitor on Lens-Induced Myopia"Ophthalmic Research. 33. 75-79 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kamei M, et al.: "Macular translocation with chorioscleral outfolding : an experimental study"American Journal of Ophthalmology. 132. 149-155 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukui T, et al.: "ABCA4 Gene Mutations in Japanese patients with Stargardt Disease and Retinitis Pigmentosa"Investigative Ophthalmology and Visual Science. 43. 2819-2824 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tano Y.: "LIX Edward Jackson Memorial Lecture-Pathologic Myopia : Where are We Now?"American Journal of Ophthalmology. 134. 645-660 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujikado T, et al.: "Reading Ability after Macular Translocation Surgery with 360-degree Retinotomy"American Journal of Ophthalmology. 134. 849-856 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujikado T, et al.: "Myopia Updates II"Springer, New York.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi, T., Nakamura, T., Hayashi, A., Kamei, M., Nakabayashi, M., Okada, A.A., Tomita, N., Kaneda, Y., Tano, Y: "Inhibition of experimental choroidal neovascularization by overexpression of tissue inhibitor of metalloproteinases-3 in retinal pigment epithelium cells"Am. J. Ophthalmol.. 130(6). 774-781 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujikado, T., Tsujikawa, K., Tamura, M., Hosohata, J., Kawasaki, Y., Tano, Y: "Effect of a Nitric Oxide Synthase Inhibitor on Lens-Induced Myopia"Ophthalmic Res.. 33(2). 75-79 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kamei M, Roth DB, Lewis H: "Macular translocation with chorioscleral outfolding: an experimental study"Am. J. Ophthalmol. 132. 149-155 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukui, T., Yamamoto, S., Nakano, K., Tsujikawa, M., Morimura, H., Nishida, K., Ohguro, N., Fujikado, T., Irifune, M., Kuniyoshi, K., Okada, A.A., Hirakata, A., Miyake, Y., Tano, Y: "ABCA4 Gene Mutations in Japanese patients with Stargardt Disease and Retinitis Pigmentosa"Invest. Ophthalmol. Vis. Sci.. 43(9). 2819-2824 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tano, Y: "LIX Edward Jackson Memorial Lecture-Pathologic Myopia:Where are We Now?"Am. J. Ophthalmol.. 134(5). 645-660 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujikado, T., Asonuma, S. Ohji, M., Kusaka, S., Hayashi, A., Ikuno, Y., Kamei, M., Oda, K., Tano, Y: "Reading Ability after Macular Translocation Surgery with 360-degree Retinotomy"Am. J. Ophthalmol.. 134(6). 849-856 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujikado T, kamei M, Tano Y, et al.: "Reading ability after macular translocation surgery with 36O-degree retinotomv"Am J Ophthalmol. 134(6). 849-856 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Crabb JW, Kamei M, et al.: "Drusen proteome analysis : an approach to the etiology of age-related macular degeneration"Proc Natl Acad Sci USA. 12;99(23). 14682-14687 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ikuno Y, Tano, et al.: "Retinal Glial Cells Stimulate Microvascular Pericyte Proliferation Via Fibroblast Growth Factor and Platelet-derived Growth Factor In Vitro"Jpn.J.Ophthalmol. 46. 413-418 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fukui T, Tano, et al.: "ABC Gene Mutations in Japanese patients with Stargardt Disease and Retinitis Pegmentose"I.O.V.S. 43(9). 2819-2824 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tano Y.: "LIX Edward Jackson Memorial Lecture-Pathologic Myopia : Where are We Now?"Am J Ophthalmol. 134(5). 645-660 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohshita T...Tano Y, et ai.: "Topographic analysis of astigmatism induced by scleral shortening in pig eyes"Grafes Archive Clinical Experimental Ophthalmology. 239(5). 382-386 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fang XY...Tano Y, et al.: "Effect of Ca(2+)-free and Mg(2+)-free BSS Plus solution on the retinal pigment epithelium and retina rabbits"American Journal of Ophthalmology. 131(4). 481-488 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohji M...Tano Y, et al.: "Magnifying prismatic lenses for vitrectomy"Japanese Journal of Ophthalmology. 45(2). 199-201 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sawa M...Tano Y, et al.: "Assessment of nuclear sclerosis after nonvitrectomizing vitreous surgery"American Journal of Ophthalmology. 132(3). 356-362 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kubota A...Tano Y, et al.: "Evaluation of the peripheral field after foveal translocation"American Journal of Ophthalmology. 132(4). 581-584 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohji M...Tano Y, et al.: "Comparison of three techniques of foveal translocation in patients with subfoveal choroidal neovascularization resulting from age-related macular degeneration"American Journal of Ophthalmology. 132(6). 888-896 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohji M...Tano Y, et al.: "New soft-tipped instruments for foveal translocation surgery with degrees retinotomy"Arch Ophthalmol. 118. 1422-1424 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Cekic O...Tano Y, et al.: "Importance of assessing functional fixation point in the treatment of recurrent subfoveal choroidal neovascularization secondary to age-related machular degeneration"American Journal of Ophthalmology. 132. 802-803 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Saishin Y...Tano Y, et al.: "Retinal fascin : functional nature, subcellular distribution, and chromosomal localization"Investigative Ophthalmology and Visual Science. 41(8). 2087-2095 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujikado T...Tano Y, et al.: "Comparison of visual function after foveal translocation with 360 degrees retinotomy and with scleral shortening in a patient with bilateral myopic neovascular maculopathy"American Journal of Ophthalmology. 130(4). 525-527 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hayashi A...Tano Y, et al.: "Retinal changes after retinal translocation surgery with scleral imbrication in dog eyes"Investigative Ophthalmology and Visual Science. 41(13). 4288-4292 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Cekic O...Tano Y, et al.: "Foveal translocation surgery and myopic subfoveal CNV membrane"Ophthalmology. 107(12). 2117-2117 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takahashi T...Tano Y, et al.: "Inhibition of experimental choroidal neovascularization by overexpression of tissue inhibitor of metalloproteinases-3 in retinal pigment epithelium cells"American Journal of Ophthalmology. 130(6). 774-781 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujikado T...Tano Y, et al.: "Visual function after foveal translocation with 360-degree retinotomy and simultaneous torsional muscle surgery in patients with myopic neovascular maculopathy."American Journal of Ophthalmology. 131(1). 101-110 (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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