| Project/Area Number |
16390495
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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 | Tokyo Medical and Dental University |
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Principal Investigator |
OHNO Kyoko Tokyo Medical and Dental University Graduate School, Ophthalmology and Visual Science, Assistant Professor, 大学院医歯学総合研究科, 准教授 (30262174)
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| Co-Investigator(Kenkyū-buntansha) |
MORITA Ikuo Tokyo Medical and Dental University Graduate School, Cellular Physiological Chemistry, Professor & Chairman, 大学院医歯学総合研究科, 教授 (60100129)
MOCHIZUKI Manabu Tokyo Medical and Dental University Graduate School, Ophthalmology and Visual Science, Professor & Chairman, 大学院医歯学総合研究科, 教授 (10010464)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥11,600,000 (Direct Cost: ¥11,600,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2004: ¥6,900,000 (Direct Cost: ¥6,900,000)
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| Keywords | amyloid β / age-related macular degeneration / choroidal neovascularization / retinal pigmented epithelium / basal deposits / neprilysin / VEGF / PEDF / 網膜色素上皮細胞 / 脈絡膜血管新生 / 血管内皮増殖因子 / 色素上皮由来因子 / ネプリライシン |
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| Research Abstract |
Drusen are extracellular deposits that lie beneath the retinal pigment epithelium (RPE) and are the earliest signs of age-related macular degeneration (AMD). Recent proteome analysis demonstrated that amyloid β(Aβ) deposition was specific to drusen from eyes with AMD. To work toward a molecular understanding of the development of AMD from drusen, we investigated the effect of Aβ on cultured human RPE cells as well as ocular findings in neprilysin gene-disrupted mice, which leads to an increased deposition of Aβ. The results showed that Aβ treatment induced a marked increase in VEGF as well as a marked decrease in pigment epithelium-derived factor (PEDF). Conditioned media from AR-exposed RPE cells caused a dramatic increase in tubular formation by human umbilical vein endothelial cells. Light microscopy of senescent neprilysin gene-disrupted mice showed an increased number of degenerated RPE cells with vacuoles. Electron microscopy revealed basal laminar and linear deposits beneath the RPE layer, but we did not observe choroidal neovascularization (CNV). The present study demonstrates that Aβ accumulation affects the balance between VEGF and PEDF in the RPE, and an accumulation of Aβ reproduces features characteristics of human AMD, such as RPE atrophy and basal deposits formation. Some other factors, such as breakdown of integrity of Bruch's membrane, might be necessary to induce CNV of AMD.
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