| Project/Area Number |
09470382
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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 | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
ISHIBASHI Tatsuro Kyushu university, Ophthalmology, Associate Professor, 大学院・医学研究院, 助教授 (30150428)
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| Project Period (FY) |
1997 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1997: ¥3,900,000 (Direct Cost: ¥3,900,000)
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| Keywords | diabetic retinopathy / VEGF / VPF / AGEs / hypoxia / glia / Bucillamine / 糖尿病 / 網膜症 / 網膜 / 網膜血管 / 組織因子 / in vitro / AGE / グリア細胞 / in vivo |
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| Research Abstract |
Diabetic retinopathy (DR), which is characterized by gradually progressive alterations in che retinal microvasculature, still remains the leading cause of blindness in the working population. Consequently, further investigation of the pathogenesis of DR is necessary to develop the better therapeutical strategy to prohibit the initiation and progression of DR.Recent studies revealed that vascular endothelial growth factor (VEGF) also known as vascular permeability factor (VPF) is involved in the pathogenesis of DR.Thus, VEGF is considered to be a possible molecular target for the treatment of DR.
We identified the significant correlation between the accumulation of advanced glycation endproducts (AGEs) and VEGF expression in diabetic retinal tissue. In vitro. AGEs stimulated not only VEGF gene expression by cutured retinal glial cells but also the expression of KDR gene, which is a major VEGF receptor, by cultured retinal capillary endothelial cells. Thus, AGEs appeared to be one of the major stimuli activating VEGF and its receptor system in diabetic retinal tissue.
Intravitreal injection of AGEs caused retinal vascular hyperpermeability in rat eyes possibly through the activation of VEGF and its receptor system. Intraperitoneal injection of Bucillamine, which is one of the anti-rheumatic drugs, inhibited AGEs-dependent retinal vascular hyperpermeability. Furtheremore, Bucillamine prohibited hypoxia-induced VEGF gene expression by cultured retinal glial cells. These results indicated that Bucillamine might be therapeutically useful for DR through the downregulation of VEGF and its receptor system.
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