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TREATMENT OF RETINAL DEGENERATIVE DISIESE BY TRANSPLANTATION OF GENE TRANSFERRED CELLS

Research Project

Project/Area Number 12357010
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Ophthalmology
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

TAMAI Makoto  TOHOKU UNIVERSITY, SCHOOL OF MEDICINE OPHTHALMOLOGY, PROFESSOR, 大学院・医学系研究科, 教授 (90004720)

Co-Investigator(Kenkyū-buntansha) SATO Hajime  TOHOKU UNIVERSITY, SCHOOL OF MEDICINE OPHTHALMOLOGY, RESEARCH ASSOCIATE, 医学部附属病院, 助手 (10312571)
YAMAGUCHI Katsuhiro  TOHOKU UNIVERSITY, SCHOOL OF MEDICINE OPHTHALMOLOGY, ASSOCIATE PROFESSOR, 医学部附属病院, 助教授 (20200610)
ABE Toshiaki  TOHOKU UNIVERSITY, SCHOOL OF MEDICINE OPHTHALMOLOGY, PROFESSOR, 大学院・医学系研究科, 教授 (90191858)
TOMITA Hiroshi  TOHOKU UNIVERSITY, SCHOOL OF MEDICINE OPHTHALMOLOGY, RESEARCH ASSOCIATE, 医学部附属病院, 助手 (40302088)
西川 真平  東北大学, 医学部・附属病院, 講師 (90261635)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥43,420,000 (Direct Cost: ¥39,700,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2002: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2001: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2000: ¥27,300,000 (Direct Cost: ¥27,300,000)
Keywordstransplantation / iris pigment epithelial cells / adeno-associate virus vector / Brain derived neurotrophic factor / アデノウイルス / 神経栄養因子
Research Abstract

Our purpose of this research is to treat retinal degenerative diseise by transplanting cells in the sub retinal space which are modified by transferring effective gene for inhibition of photoreceptor degeneration. To achieve this purpose, we were planning to use the iris pigment epithelial (IPE) cells as a candidate for the transplanting cells. The advantage of using IPE cells is to be possible to do the autolougous cell transplantation. IPE cells could be obtained from the eye easily and maintain under the culture. To transfer the gene to IPE cells in vitro which has the protective effect on the photoreceptor degeneration makes possible to transfer the target cells only.
We have clarified below five things for 3 years.
1. IPE cell has similar properties with the retinal pigernent epithelial cells. 2. When IPE cells were transplanted into sub retinal space, IPE cells have been survived in the transplanted area for 6 months. 3. The transplanted IPE cells had the phagocytic activity like RPE cells, which indicated transplanted IPE cells functionally worked in sub-retinal space. 4. We could not any adverse effect caused by the IPE transplantation. 5. It has been reported adenovirus caused systemic infection which induced inflammatory response when adenovirus vector was used for the gene transfer. Our study showed possibilities that in vitro transfer of gene made systemic infection rate decrease even if the adenovirus vector was used for the gene transfection. However we found that adeno-associated virus vector were useful for the gene transfer in view of expression periods and adverse effect. The transplantation of BDNF transferred IPE cells has protective effects on retinal degeneration induced by light or glutamate toxicity.

Report

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

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Ito, A., et al.: "Distribution of organic anion-transporting polypeptide 2 (oatp2) and oatp3 in the rat retina"Invest Ophthalmol Vis Sci. 43(3). 858-863 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kano, T., et al.: "Protective effect against ischemia and light damage of iris pigment epithelial cells transfected with the BDNF gene"Invest Ophthalmol Vis Sci. 43(12). 3744-3753 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sato, H., et al.: "Retinitis pigmentosa associated with ectopia lentis"Arch Ophthalmol. 120(6). 852-854 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomita, H., et al.: "Nipradilol inhibits apoptosis by preventing the activation of caspase-3 via S-nitrosylation and the cGMP-dependent pathway"Eur J Pahrmacol. 452(3). 263-268 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Udono, T., et al.: "Elevated immunoreactive-adrenomedullin levels in the aqueous humor of patients with uveitis and vitreoretinal disorders"Peptides. 23(10). 1865-1868 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida, M., et al.: "Two types of optical coherence tomographic images of retinal pigment epithelial detachments with different prognosis"Br J Ophthalmol. 86(7). 737-739 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 富田, 玉井: "Molecular Medicine 39巻 網膜・視神経の発生と再生"中山書店. 266 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ito, A., et al.: "Distribution of organic anion-transporting polypeptide 2 (oatp2) and oatp3 in the rat retina."Invest Ophthalmol. VisSci43(3). 858-863 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kano, T., et al: "Protective effect against ischemia and light damage of iris pigment epithelial cells transfected with the BDNF gene"Invest Ophthalmol. VisSci43(12). 3744-3753 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sato H., et al.: "Retinitis pigmentosa associated with ectopia lentis."Arch Ophthalmol. 120(6). 852-854 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomita, H., et al.: "Nipradilol inhibits apoptosis by preventing the activation of caspase-3 via S-nitrosylation and the cGMP-dependent pathway."EurJ Pharmacol. 452(3). 263-268 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Udono, T., et al.: "Elevated immunoresctive-adrenomedullin levels in the aqueous humor of patients with uveitis and vitreoretinal disorders."Peptides. 23(10). 1865-1868 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida, M., et al.: "Two types of optical coherence tomographic images of retinal pigment epithelial detachments with different prognosis"Br J Ophthalmol. 86(7). 737-739 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomita, H., Tamai, M, et al: "Molecular Medicine-39"Nakayama syoten. 266 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ito, A., et al.: "Distribution of organic anion-transporting polypeptide 2(oatp2)and oatp3 in the rat retina"Invest Ophthalmol Vis Sci. 43(3). 858-63 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kano, T., et al.: "Protective effect against ischemia and light damage of iris pigment epithelial cells transfected with the BDNF gene"Invest Ophthalmol Vis Sci. 43(12). 3744-53 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sato, H., et al.: "Retinitis pigmentosa associated with ectopia lentis"Arch Ophthalmol. 120(6). 852-4 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tomita, H., et al.: "Nipradilol inhibits apoptosis by preventing the activation of caspase-3 via S-nitrosylation and the cGMP-dependent pathway"Eur J Pharmacol. 452(3). 263-8 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Udono, T., et al.: "Elevated immunoreactive-adrenomedullin levels in the aqueous humor of patients with uveitis and vitreoretinal disorders"Peptides. 23(10). 1865-8 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshida, M., et al.: "Two types of optical coherence tomographic images of retinal pigment epithelial detachments with different prognosis"Br J Ophthalmol. 86(7). 737-9 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 富田, 玉井: "網膜・視神経の発生と再生"Molecular Medicine. 266 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sakuragi M., Tomita H., Abe T., Tamai M.: "Changes of phagocytic capacity in basic fibroblast growth factor-transfected iris pigment epithelial cells in rats"Current Eye Research. 23(3). 185-191 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Abe T., Abe K., Tsuda T., Itoyama Y., Tamai M.: "Ophthalmological findings in patients with spinocerebellar ataxia type 1 are not correlated with neurological anticipation"Graefes Archive for Clinical & Experimental Ophthalmology. 239(10). 722-728 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Suzuki T., Takahashi K., Kuwahara S., Wada Y., Abe T., Tamai M: "A novel (Pro79Thr) mutation in the FKHL7 gene in a Japanese family with Axenfeld-Rieger syndrome"American Journal of Ophthalmology. 132(4). 572-575 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Wada Y., Abe T., Takeshita T., Sato H., Yanashima K., Tamai M.: "Mutation on human retinal fascin gene (FSCN2) causes autosomal dominant retinitis pigmentosa"Investigative Ophthalmology & Visual Science. 42(10). 2395-2400 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Wada Y., Abe T., Sato H., Tamai M.: "A novel Gly35Ser mutation in the RDH5 gene in a Japanese family with fundus albipunctatus associated with cone dystrophy"Archives of Ophthalmology. 119(7). 1059-1063 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Udono T., Takahashi K., Nakayama M., Yoshida A., Totsune K., Murakami O., Durlu YK., Tamai M., Shihahara S.: "Induction of adrenomedullin by hypoxia in cultured retinal pigment epithelial cells"Investigative Ophthalmology & Visual Science. 42(5). 1080-1086 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Abe T et al.: "Auto iris pigment epithelial cell transplantation in patients with age-related macular degeneration : Short-term results."Tohoku Journal of Experimental Medicine. 191. 7-20 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Udono T et al.: "Increased expression of adrenomedullin mRNA in the tissues of intraocular and orbital tumors."American Journal of Ophthalmology. 129. 555-556. (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sato M et al.: "Analysis of the metallothionein gene in age-related macular degeneration."Japanese Journal of Ophthalmology. 44. 115-121 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Abe T et al.: "Variable R1 region in varicella tester virus in fulminant type of acute retinal necrosis syndrome."British Journal of Ophthalmology.. 84. 193-198 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wade Y et al.: "A new Leu253Arg mutation in the RP2 gene in a Japanese family with X-linked retinitis pigmentosa."Investigative Ophthalmology & Visual Science . 41. 290-293 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Abe T et al: "Autologous iris pigment epithelial cell transplantation in monkey subretinal region."Current Eye Research. 20. 268-275. (2000)

    • Related Report
      2000 Annual Research Report

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

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