2001 Fiscal Year Final Research Report Summary
Control of Ocular Proliferation and Neuroprotection by Gene Therapy and Analysis of These Molecular Mechanisms.
| Project/Area Number |
12671730
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Kansai Medical University |
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Principal Investigator |
OGATA Nahoko Kansai Med Univ. Ophthalmology Assistant Professor, 医学部, 講師 (60204062)
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| Co-Investigator(Kenkyū-buntansha) |
KANEDA Yasufumi Osaka Univ. Division of Gene Therapy, Professor, 大学院・医学研究科・遺伝子治療学講座, 教授 (10177537)
MATSUMURA Miyo Kansai Medical University Department of Ophtahlmology, Professor, 医学部, 教授 (30144380)
YAMAMOTO Chikako Kansai Medical University Department of Ophtahlmology, Instructor, 医学部, 助手 (80288844)
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| Project Period (FY) |
2000 – 2001
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| Keywords | diabetic retinopathy / PEDF / angiogenesis / retinal pigment epithelium / VEGF / Gene therapy / choroidak neovascularization / HVJ-liposome |
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| Research Abstract |
We determine the changes in the expression of cytokines in cultured human retinal pigment epithelial (RPE) cells and rat retinas after laser photocoagulation. We found an up-regulation of pigment epithelium-derived factor (PEDF) and a down-regulation of angiogenic factors, i.e., vascular endothelial growth factor (VEGF) and suggested that PEDF play a role in inhibiting neovascularization by its anti-angiogenic activity.
We also investigated the expression of PEDF and VEGF in a rat model of experimental choroidal neovascularization (CNV) and demonstrated that PEDF attributes the regression of CNV. We evaluated the transfection of LacZ gene and double stranded oligodeoxynucleotides(=decoy) by means of the hemagglutinating virus of Japan (HVJ) liposome method with intravitreal injection in a same model. The transfected decoy against NFk-B had effectively inhibited the development of CNV. Thus, our results suggest that the HVJ liposome method can be used as a gene therapy system for regulat
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ion of angionenic factors to treat the CNV in vivo.
Ischemia-reperfusion injury model is a kind of retinal degeneration model which shows apoptosis in retina neuronal cells. Administration of PEDF had showed neuroprotective effects on retinal cells. Therefore, PEDF would be useful inpreventing neuronal degeneration in the inner retina resulting from ischemia.
We reported the levels of PEDF and VEGF in the vitreous of patients with diabetic retinopathy, rhegmatogenous retinal detachment and priliferative vitreoretinopathy. PEDF in the vitreous was low in diabetic retinopathy and proliferative vitreoretinopathy, but high in rthgmatogenous retinal detachment. These results suggest that PEDF inhibits angiogenesis and cell proliferation, and that lower leverls of PEDF may result in active proliferative diabetic retinopathy and proliferative vitreoretinopathy. The results also suggest that higher levels of PEDF in the eyes with rhegmatogenous retinal detachment may act as a neuroprotective agent for the detached retina. Less
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[Publications] Soichiro Fujiyama, Hiroaki Matsubara, Yoshihisa Nozawa, Katsuya Maruyama, Yasuhiro Mori, Yoshiaki Tsutsumi, Hiroya Masaki, Yoko Uchiyama, Yoko Koyama, Atsuko Nose, Osamu Iba, Eriko Tateishi, Nahoko Ogata, et.al.: "Angiotensin AT1 and AT2 receptors differentially regulate Angiotensin-2 and vascular endothelial growth factor expression and angiogenesis by modulating heparin binding-epidermal growth factor (EGF) -mediated EGF receptor transactivation."Circulation Research.. Vol. 88. 22-29 (2001)
Description
「研究成果報告書概要(欧文)」より
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