2002 Fiscal Year Final Research Report Summary
Development of bioactive substance delivery system to the vitreous and retina with biodegradable hydrogels
| Project/Area Number |
12557148
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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 | Nagoya City University |
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Principal Investigator |
OGURA Yuichiro Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院・医学研究科, 教授 (70191963)
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| Co-Investigator(Kenkyū-buntansha) |
KUWANO Mitsuaki Santen Pharmaceutical. Co., Ophthalmic Research Division, General Manager, 眼科動態研究グループ, グループ長
TABATA Yasuhiko Kyoto University, Institute for Frontier Medical Sciences, Professor, 再生医科学研究所, 教授 (50211371)
KIMURA Hideya Nagoya City University, Graduate School of Medecal Sciences, Assosiate Professor, 大学院・医学研究科, 助教授 (50252440)
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| Project Period (FY) |
2000 – 2002
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| Keywords | biodegradable polymes / hydrogels / bioactive proteins / interferon / choroidal neovascularization |
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| Research Abstract |
Targeting and inhibitory effects of IFN combined with dextran on experimental choroidal neovascularization (CNM) were studied. Interferon (IFN) β was conjugated to dextran, which has metal-chelating, diethylenetriaminepentaacetic acid (DTPA) residues. Based on metal coordination, conjugation of IFNβ with DTPA-dextran resulted from simply mixing both substances in an aqueous solution containing Zn^<2+>. The effects of IFNβ on the proliferation human umbilical vein endothelial cells (HUVECs) and bovine retinal pigment epithelial cells (BRPECs) were evaleated. To evaluate the activity loss of IFNβ by conjugation, the effect of the conjugate on HUVECs was compared with that of IFNβ. Experimental CNV was induced by subretinal injection of gelatin microspheres containing basic fibroblast growth factor in rabbits. The rabbits with CNV were intravenously treated twice weekly with 7.5 million international units (MIU)/kg per day free IFNβ (for 4 weeks), with IFNβ-DTPA-dextran conjugate containing 7.5 (for 2 weeks) or 0.75 (for 4 weeks) MIU/kg per day IFNβ, or with saline. The effects of these substances were evaluated by fluorescein angiography and histology. To observe the accumulation of conjugate, the doses of IFNβ in CNV tissues were measured by enzyme-linked immunosorbent assay. IFNβ inhibited the growth of HUVECs and enhanced the proliferation of BRPECs. The conjugate seemed to preserve approximately 44% of IFNβ activity. Although both doses of IFNβ-DTPA-dextran inhibited progression of CNV in rabbits, longer term administration of a lower dose of IFNβ-DTPA-dextran had a sustained inhibitory effect on progression of CNV (P<0.05). Histologic studies revealed the inhibitory effect of IFNβ-DTPA-dextran on progression of CNV. This conjugate prolonged the plasma half-life of IFNβ and enabled IFNβ to accumulate the CNV in rabbits.
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