Journal Article
Eicosapentaenoic acid is anti-inflammatory in preventing choroidal neovascularization in mice
Koto, T; Nagai, N; Mochimaru, H; Kurihara, T; Izumi-Nagai, K; Satofuka, S; Shinoda, H; Noda, K; Ozawa, Y; Inoue, M; Tsubota, K; Oike, Y; Ishida, S
Investigative Ophthalmology and Visual Science
ISSN: 0146-0404
EISSN: 1552-5783
PURPOSE: To investigate the role of eicosapentaenoic acid (EPA), the major omega-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 omega-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 omega-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 omega-3 PUFAs may prevent CNV and lower the risk of blindness due to age-related macular degeneration.
5,8,11,14,17 icosapentaenoic acid; antiinflammatory agent; C reactive protein; intercellular adhesion molecule 1; interleukin 6; linoleic acid; messenger RNA; monocyte chemotactic protein 1; vasculotropin; antiinflammatory agent; Ccl2 protein, mouse; fatty acid; Icam1 protein, mouse; icosapentaenoic acid; intercellular adhesion molecule 1; interleukin 6; linoleic acid; messenger RNA; monocyte chemotactic protein 1; unclassified drug; vascular endothelial growth factor A, mouse; vasculotropin A; animal cell; animal experiment; animal model; article; cell stimulation; choroid; controlled study; enzyme linked immunosorbent assay; gas chromatography; high performance liquid chromatography; in vitro study; laser coagulation; lipid composition; macrophage; mouse; nonhuman; pigment epithelium; priority journal; protein expression; reverse transcription polymerase chain reaction; subretinal neovascularization; supplementation; animal; blood; C57BL mouse; choroid; diet; disease model; drug effect; genetics; metabolism; subretinal neovascularization; vascular endothelium; Animals; Anti-Inflammatory Agents; Chemokine CCL2; Choroid; Choroidal Neovascularization; Chromatography, Gas; Chromatography, High Pressure Liquid; Diet; Disease Models, Animal; Eicosapentaenoic Acid; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Fatty Acids; Intercellular Adhesion Molecule-1; Interleukin-6; Laser Coagulation; Linoleic Acid; Macrophages; Mice; Mice, Inbred C57BL; Pigment Epithelium of Eye; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Vascular Endothelial Growth Factor A