| Project/Area Number |
17591833
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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 | Osaka University |
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Principal Investigator |
KAMEI Motohiro Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (40281125)
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| Co-Investigator(Kenkyū-buntansha) |
TANO Yasuo Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (80093433)
GOMI Fumi Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (80335364)
IKUNO Yasushi Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (50294096)
OHJI Masahito Shiga Medical College, Professor, 医学部, 教授 (90252650)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Age-related macular degeneration / Choroidal neovascularization / oxidized lipoprotein / scavenger receptor / macrophage / oxidative stress / phototoxicity / atherosclerosis / 酸化リポ蛋白 / スカベンジャーレセプター |
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| Research Abstract |
We performed immunohistochemistry on 10 surgically-excised choroidal neovascular (CNV) membranes from eyes with age-related macular degeneration (AMD). and found oxidized lipoproteins were immunohistochemically detected in the CNV membranes. Cells expressing scavenger receptors were found to be predominantly macrophages with a minority of RPE. Both SR-PSOX and LOX-1 mRNAs were detected in CNV membranes. We, then, investigated whether oxidized phospholipids were present in normal eyes and whether the level changed with increasing age. Immunohistochemistry showed that oxidized phosphatidylcholine was present in the photoreceptors and retinal pigment epithelium of the normal human macular area, and their levels increased with age. Eyes with AMD showed more intense immunoreactivity for oxidized phospholipids than age-matched normal eyes.
We induced oxidized phospholipids in mice retina with blue light irradiation, and compared reactions between 2-and 12-month-old C57/BL6 mice. We found that induced oxidized phospholipids in the retina increase with age and oxidized phospholipids may stimulate expression of monocyte chemotactic protein-1 (MCP-1) in the RPE. We, then, injected oxidized phospholipids into the subretinal space and found increase of MCP-1 and CNV formation at high rate. Mice with MCP-1 knockout or Ccr-2 knockout showed no formation of CNV. Our findings suggest that aging may make the retina subjected to oxidative stress and oxidized phospholipids and MCP-1 may play an important role in AMD pathogenesis.
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