May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
The Pathogenic Role of Oxidized Phospholipids in Age-Related Macular Degeneration
Author Affiliations & Notes
  • M. Suzuki
    Ophthalmology, Osaka Univ Medical School, Suita, Japan
  • M. Kamei
    Ophthalmology, Osaka Univ Medical School, Suita, Japan
  • H. Itabe
    Biological Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan
  • Z.-J. Du
    Ophthalmology, Osaka Univ Medical School, Suita, Japan
  • K.-H. Sonoda
    Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  • M. Tsujikawa
    Ophthalmology, Osaka Univ Medical School, Suita, Japan
  • Y. Tano
    Ophthalmology, Osaka Univ Medical School, Suita, Japan
  • Footnotes
    Commercial Relationships  M. Suzuki, None; M. Kamei, None; H. Itabe, None; Z. Du, None; K. Sonoda, None; M. Tsujikawa, None; Y. Tano, None.
  • Footnotes
    Support  Grant-in-Aid for Scientific Research (#15591853) from the Ministry of Education, Science and Culture of Japan
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5417. doi:https://doi.org/
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    • Get Citation

      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. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: age-related macular degeneration • oxidation/oxidative or free radical damage • inflammation 
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