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M. Suzuki, M. Kamei, H. Itabe, Z.-J. Du, K.-H. Sonoda, M. Tsujikawa, Y. Tano; The Pathogenic Role of Oxidized Phospholipids in Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5417.
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We previously reported that oxidized phospholipids increase in the human retina with age and in age-related macular degeneration (AMD). The aim of this study was to establish an animal model with increased oxidized phospholipids and to investigate the pathogenic role of oxidized phospholipids in AMD, especially via inflammatory processes.
Freely moving 2- and 12-month-old C57BL/6 mice were subjected to continuous blue light irradiation (2.0 mW/cm2, transmission peak wavelength: 480 nm) for 1 week. Retinas of the mice were then removed, and immunohistochemistry and competitive enzyme-linked immunosorbent assay (competitive ELISA) was performed to evaluate the distribution and quantity of oxidized phospholipids. We also performed immunohistochemistry and ELISA to estimate monocyte chemotactic protein (MCP)-1 expression in these retinas. ARPE-19 cells were cultured with oxidized phospholipids and the supernatants were assessed for MCP-1 by ELISA. To address whether oxidized phospholipids contribute to choroidal neovascularization (CNV) formation, oxidized phospholipids were subretinally injected and histological examination was performed.
A significant (p<0.001) amount of oxidized phospholipids was induced after light irradiation. The relative amount of oxidized phospholipids in the 12-month-old light irradiated mice was greater than in the 2-month-old mice (p<0.001). Positive staining for MCP-1 was observed in the retinal pigment epithelium (RPE) and choroid of the 12-month-old light irradiated mice. A significant (p<0.001) amount of MCP-1 was induced after light irradiation and increased with age (p<0.001). Oxidized phospholipids induced MCP-1 production in the RPE in a dose dependent manner. Subretinal injection of oxidized phospholipids induced CNV with positive staining for macrophages.
These results indicate that light irradiation can induce phospholipid oxidation in the retina, and therefore old individuals may become more susceptible to light irradiation. Furthermore, oxidized phospholipids may stimulate expression of MCP-1 in the RPE. Successful development of CNV strongly suggests that the inflammatory pathway induced by oxidized phospholipids plays an important role in AMD pathogenesis.
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