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M. Suzuki, M. Tsujikawa, H. Itabe, K.-H. Sonoda, K. Egashira, M. Kamei; The Involvement of Oxidized Phospholipids in Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2780.
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We previously reported that subretinal injection of oxidized phospholipids induce choroidal neovasuclarization (CNV) with positive staining for macrophages. This study is to investigate whether subretinally-injected oxidized phospholipids induce expression of monocyte chemoattractant protein-1 (MCP-1), a chemotactic factor of macrophages and whether MCP-1 plays a key role in this experimental CNV formation.
C57BL/6 mice (n=8) were subjected to subretinal injection with oxidized phospholipids and untreated phospholipids as control. One month after the injection we performed immunohistochemistry to estimate MCP-1 expression and the distribution of macrophages. To investigate whether MCP-1 plays a key role in this experimental CNV formation, we injected oxidized phospholipids into the subretinal space of two knock-out mouse lines, MCP-1-/- (n=8) and Ccr2-/-(MCP-1 receptor) (n=8) mice and histological examination was performed. We also evaluated the volume of the induced CNV.
Immunohistochemistry revealed that more MCP-1 was present in the retinal pigment epithelium (RPE) and choroid and more macrophages were also observed with subretinal injections of oxidized phospholipids than in the controls. In both MCP-1-/- mice and Ccr2-/- mice no CNV developed due to subretinal injections of oxidized phospholipids, whereas CNV developed in all of the eyes of wild type siblings. The mean volume of CNV in the eyes of wild type mice with subretinally-injected oxidized phospholipids was 2.96±0.79 x 104 µm3 (p<0.001). MCP-1 was induced in the RPE and choroid of Ccr2-/- mice as well as in those of the wild type siblings and as might be expected, MCP-1-/- mice showed no immunoreactivity with MCP-1. No macrophage accumulation was detected in either Ccr2-/- mice or MCP-1-/- mice.
These results indicate that subretinal injection of oxidized phospholipids induce CNV via the MCP-1 pathway. This study is the first to link oxidized phospholipids and CNV formation via an inflammatory reaction.
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