| 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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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | diabetic retinopathy / PEDF / angiogenesis / retinal pigment epithelium / VEGF / Gene therapy / choroidak neovascularization / HVJ-liposome / 網膜剥離 / 光凝固 / 神経保護 / 網膜変性 / HVJ-リポソーム / 神経細胞死 |
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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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