2004 Fiscal Year Final Research Report Summary
Development of new treatment modalities for age-related macular degeneration
| Project/Area Number |
15591845
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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 | The University of Tokyo |
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Principal Investigator |
TAMAKI Yasuhiro The University of Tokyo, Faculty of Medicine, Assistant Professor, 医学部附属病院, 助教授 (20217178)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAI Ryouzo The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (60207975)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Kruppel-like Factor / Neovascularization / Tissue factor pathway inhibitor-2 / animal model of retinal degeneration / laser-induced CNV / COX-2 |
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| Research Abstract |
Firstly, using the mice lacking one allele of the Intestinal Kruppel-like Factor (IKLF) gene (IKLF (+/-) mice). the role of IKLF was investigated in the pathological retinal neovascularization using a model of the retinopathy of prematurity (ROP). First, the retina and its vessels of the IKLF (+/-) mice were normal. Next, in the ROP model, neovascularity was decreased by 74% in the KLF-1 (+/-) mice compared to the controls (p=0.0317). IKLF is dispensable for the normal retinal vascular proliferation and but is involved in pathological retinal neovascularization in vivo
Secondly, we investigated the in vivo effects of tissue factor pathway inhibitor 2 (TFPI-2), which stimulates proliferation of retinal pigment epithelial cells, but not the proliferation of fibroblast and vascular endothelial cells in vitro, on retinal degeneration using sodium-iodate (SI) induced model in rabbits and Royal College of Surgeons (RCS) rats. The recombinant TFPI-2 (rTFPI-2)-treated eyes showed significantly
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less decrease in the relative amplitude of the c-wave than control eyes after 20mg/kg of SI was intravenously administered. Additionally, The thickness of the outer nuclear layer was significantly thicker and the vacuole in the photoreceptor layer was less frequently observed in the rTFPI-2-treated RCS rats than the controls. These findings suggest that TFPI-2 rescues SI-induced retinal degeneration in rabbits and naturally occurring retinal degeneration in RCS rats at least partly.
Lastly, we investigated the anti-angiogenic effect of etodolac, cyclooxygenase (COX)-2 specific inhibitor, which inhibit cell proliferation and tubular morphogenesis of vascular endothelial cells in a murine model of choroidal neovascularization (CNV). Oral administration of etodolac significantly inhibited the induction of CNV by grade of fluorescence leakage compared to the controls. Both CNV membrane cross-sectional area and blood vessel lumen cross-sectional area were significantly decreased. The CNV inhibition by oral administration of etodolac suggests that COX-2 is related in the induction of experimentally induced CNV in the mice. Less
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