| Project/Area Number |
17591842
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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 | Kumamoto University |
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Principal Investigator |
TSUTSUI Junichiro Kumamoto University, University Hospital, staff surgeon, 医学部附属病院, 医員 (60264404)
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| Co-Investigator(Kenkyū-buntansha) |
TANIHARA Hidenobu Kumamoto University, Faculty of Medical and Pharmaceutical Sciences, Professor, 大学院医学薬学研究部, 教授 (60217148)
KOGA Takahisa Kumamoto University, University Hospital, Lecturer, 医学部附属病院, 講師 (70372787)
ITO Yasuhiro Kumamoto University, University Hospital, Research Associate, 医学部附属病院, 助手 (70380996)
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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 |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | scavenger receptor / LOX-1 / choroidal neovascularization / Age-related macular degeneration / statin / 脈絡膜新生血管 |
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| Research Abstract |
1. Macrophage cells accumulated in choroidal neovascular membranes excised surgically during submacular operation. A portion of them was positively immunostained with antibodies against Class-A scavenger receptors (SR-A) that were important for aterosclerosis. Neovascular membranes other than Age-related macular degeneration also contained SR-A positive macrophage cells. It is possibile that scavenger receptors have an important role for the choroidal neovascularization.
2. The experimental models of laser-induced choroidal neovascularization (CNV) were prepared in wild type and LOX-1 gene knockout (LOX-1 KO) mice. The expression of LOX-1 mRNA was induced after exposure. The protein level of precursor matrix metalloproteinases (MMPs) was increased and MMPs were activated in wild mice, but in LOX-1 KO mice, the expression of precursor MMPs and activation of MMPs were suppressed. In wild type mice neovascularity within the laser-exposed area was detected with 93 %, but in LOX-1 KO mice it
… More
was reduced with 43 %. These data suggest that LOX-1 may promote the choroidal neovascularization.
3. To evaluate the effect of the administration of the 3-hydroxy-3-methylglutaryl co-enzyme A(HMG-CoA) reductase inhibitors (pitavastatin) on CNV, that was known to suppress hyperlipidemia and plaque formation in atherosclerosis, the experimental models of laser-induced CNV was created in rats. Pitavastatin-treated rats had significantly less fluorescence leakage in laser-exposed area. Both the area and the thickness of CNV in pitavastatin-treated rais were significantly reduced compared with control. These indicate that the therapeutic dose of pitavastatin effectively suppressed experimental CNV in rats.
4. In order to screen the protein cotained in the human intraocular fluid, the proteomics analysis was applied to get the two-dimensional electrophoresis profile; from the aqueous humors excised surgically during cataract operations. The silver-staining protein spots were picked up and identified by matrix-a: sisted laser desorption/ionization time-of-flight mass spectrometry and data base searching. Alubmin, alloalubmin, transferrin, apolipoprotein, vitamin D binding protein, transthretin, and antitrypsin were major proteins in the human aqueous humors Less
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