RT Journal Article
A1 Koto, Takashi
A1 Nagai, Norihiro
A1 Mochimaru, Hiroshi
A1 Kurihara, Toshihide
A1 Izumi-Nagai, Kanako
A1 Satofuka, Shingo
A1 Shinoda, Hajime
A1 Noda, Kousuke
A1 Ozawa, Yoko
A1 Inoue, Makoto
A1 Tsubota, Kazuo
A1 Oike, Yuichi
A1 Ishida, Susumu
T1 Eicosapentaenoic Acid Is Anti-Inflammatory in Preventing Choroidal Neovascularization in Mice
JF Investigative Ophthalmology & Visual Science
JO Invest. Ophthalmol. Vis. Sci.
YR 2007
DO 10.1167/iovs.06-1148
VO 48
IS 9
SP 4328
OP 4334
SN 1552-5783
AB   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. 
RD 4/22/2021
UL https://doi.org/10.1167/iovs.06-1148