| Project/Area Number |
12557145
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Ophthalmology
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| Research Institution | Hirosaki University |
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Principal Investigator |
NAKAZAWA Mitsuru Hirosaki University, School of Medicine, Ophthalmology, Professor, 医学部, 教授 (80180272)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Yukihiko Hirosaki University, University Hospital, Ophthalmology, Assistant Professor, 医学部附属病院, 講師 (40292148)
OHGURO Hiroshi Hirosaki University, School of Medicine, Ophthalmology, Associate Professor, 医学部, 助教授 (30203748)
ISHIGURO Seiichi Hirosaki University, School of Agriculture and Bioscience, Cell Technology, Professor, 農学生命科学部, 教授 (20111271)
久保 勝文 弘前大学, 医学部・附属病院, 助手 (00292160)
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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 |
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 2002: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2001: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2000: ¥5,500,000 (Direct Cost: ¥5,500,000)
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| Keywords | retinitis pigmentosa / gene transfer / gene therapy / electroporation / conjunctiva / glaucoma / retina |
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| Research Abstract |
Retinitis pigmentosa is a complex of hereditary progressive retinal degenerations that is nominated as the third commonest cause of legal blindness in adult population in Japan with an incidence of 1 out of 3,500 people, and therefore is an important disease in terms of the policy against blindness. Gene therapy, retinal transplantation and visual prosthesis have been currently studied by many researchers in the world, and expected to be developed as effective treatment. In this study, we investigated the technical possibility and effect of in vivo gene transfer to the retina by electroporation as a method of gene therapy for retinal degeneration. To test the technical possibility, we employed pars plana vitrectomy on the rabbit eyes to approach the retina, injected DNA solution in the subretinal space, and applied electroporation with a needle electrodes. The result indicated that this method could transfer DNA only in a small area of the retina, which might be insufficient to cause t
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herapeutic effects. It also indicated that we needed to develop another type of electrodes such as cup-shaped one. As the second part of the study, we studied the expression and effect of electroporatic gene transfer to the ocular tissue. First of all, we employed conjunctival tissue as a target of gene transfer prier to the retina, because it seemed easier to transfer DNA to the conjunctiva than to the retina. The result showed that the green fluorescent protein transferred to the conjunctiva by electroporation had been apparently expressed in the target tissue 30 days after transfer. Then we tried to transfer metalloproteinase 3 cDNA to the conjunctival flap during trabeculectomy on the rabbit eyes to examine the effect of the gene on intraocular pressure in the postoperative period. The result indicated that postoperative intraocular pressure of the eye treated with gene transfer showed as low as the eye treated by trabeculectomy with MMC, and that there was no pathological reaction in the area where DNA had been injected. All these results have suggested that we successfully transferred DNA fragments to the conjunctiva prier to the retinal, that it is possible for us to perform gene transfer to the retina using electroporation with some modification, and that gene therapy can be applied to glaucoma filtration surgery. Less
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