@article{10.1167/iovs.06-1148,
    author = {Koto, Takashi and Nagai, Norihiro and Mochimaru, Hiroshi and Kurihara, Toshihide and Izumi-Nagai, Kanako and Satofuka, Shingo and Shinoda, Hajime and Noda, Kousuke and Ozawa, Yoko and Inoue, Makoto and Tsubota, Kazuo and Oike, Yuichi and Ishida, Susumu},
    title = "{Eicosapentaenoic Acid Is Anti-Inflammatory in Preventing Choroidal Neovascularization in Mice}",
    journal = {Investigative Ophthalmology & Visual Science},
    volume = {48},
    number = {9},
    pages = {4328-4334},
    year = {2007},
    month = {09},
    abstract = "{  purpose. To investigate the role of eicosapentaenoic acid (EPA), the major ω-3 polyunsaturated fatty acid (PUFA), in the development of choroidal neovascularization (CNV), together with underlying molecular mechanisms.  methods. Six-week-old C57BL/6 mice were fed with laboratory chow with 5\\% EPA or the ω-6 PUFA linoleic acid (LA) for 4 weeks. Laser photocoagulation was performed to induce CNV, and the volume of CNV tissue was evaluated by volumetric measurements. The expression and production of intercellular adhesion molecule (ICAM)-1, monocyte chemotactic protein (MCP)-1, vascular endothelial growth factor (VEGF) and interleukin (IL)-6 in the retinal pigment epithelium (RPE)-choroid in vivo, and stimulated b-End3 endothelial cells and RAW264.7 macrophages in vitro were evaluated by RT-PCR and ELISA. Fatty acid composition in the serum and the RPE-choroid was analyzed by gas chromatography and high-performance liquid chromatography, respectively. Serum levels of C-reactive protein (CRP), IL-6, VEGF, MCP-1, and soluble ICAM-1 were examined by ELISA.  results. The CNV volume in EPA-fed animals was significantly suppressed compared with that in control mice, whereas the LA-rich diet did not affect CNV. The mRNA expression and protein levels of ICAM-1, MCP-1, VEGF, and IL-6 after CNV induction were significantly reduced in EPA-supplemented mice. In vitro, EPA application led to significant inhibition of mRNA and protein levels of ICAM-1 and MCP-1 in endothelial cells and VEGF and IL-6 in macrophages. EPA-fed mice exhibited significantly higher levels of EPA and lower levels of the ω-6 PUFA arachidonic acid in the serum and the RPE-choroid than control animals. EPA supplementation also led to significant reduction of serum levels of IL-6 and CRP after CNV induction.  conclusions. The present study demonstrates for the first time that an EPA-rich diet results in significant suppression of CNV and CNV-related inflammatory molecules in vivo and in vitro. These results suggest that frequent consumption of ω-3 PUFAs may prevent CNV and lower the risk of blindness due to age-related macular degeneration. }",
    issn = {1552-5783},
    doi = {10.1167/iovs.06-1148},
    url = {https://doi.org/10.1167/iovs.06-1148},
    eprint = {https://arvojournals.org/arvo/content\_public/journal/iovs/932943/z7g00907004328.pdf},
}