Eicosapentaenoic acid is anti-inflammatory in preventing choroidal neovascularization in mice

Takashi Koto, Norihiro Nagai, Hiroshi Mochimaru, Toshihide Kurihara, Kanako Izumi-Nagai, Shingo Satofuka, Hajime Shinoda, Kousuke Noda, Yoko Ozawa, Makoto Inoue, Kazuo Tsubota, Yuichi Oike, Susumu Ishida

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Abstract

PURPOSE. To investigate the role of eicosapentaenoic acid (EPA), the major ω-3 polyunsaturated fatty acid (PUFA), in the development of choroidal neovascularization (CNTV), 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, MCP1, 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.

Original languageEnglish
Pages (from-to)4328-4334
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume48
Issue number9
DOIs
Publication statusPublished - 2007 Sep

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Choroidal Neovascularization
Eicosapentaenoic Acid
Anti-Inflammatory Agents
Intercellular Adhesion Molecule-1
Interleukin-6
Vascular Endothelial Growth Factor A
Choroid
Retinal Pigment Epithelium
Chemokine CCL2
Unsaturated Fatty Acids
Linoleic Acid
Serum
C-Reactive Protein
Endothelial Cells
Enzyme-Linked Immunosorbent Assay
Macrophages
Diet
Messenger RNA
Light Coagulation
Macular Degeneration

ASJC Scopus subject areas

  • Ophthalmology

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Eicosapentaenoic acid is anti-inflammatory in preventing choroidal neovascularization in mice. / Koto, Takashi; Nagai, Norihiro; Mochimaru, Hiroshi; Kurihara, Toshihide; Izumi-Nagai, Kanako; Satofuka, Shingo; Shinoda, Hajime; Noda, Kousuke; Ozawa, Yoko; Inoue, Makoto; Tsubota, Kazuo; Oike, Yuichi; Ishida, Susumu.

In: Investigative Ophthalmology and Visual Science, Vol. 48, No. 9, 09.2007, p. 4328-4334.

Research output: Contribution to journalArticle

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 2007, 'Eicosapentaenoic acid is anti-inflammatory in preventing choroidal neovascularization in mice', Investigative Ophthalmology and Visual Science, vol. 48, no. 9, pp. 4328-4334. https://doi.org/10.1167/iovs.06-1148
Koto, Takashi ; Nagai, Norihiro ; Mochimaru, Hiroshi ; Kurihara, Toshihide ; Izumi-Nagai, Kanako ; Satofuka, Shingo ; Shinoda, Hajime ; Noda, Kousuke ; Ozawa, Yoko ; Inoue, Makoto ; Tsubota, Kazuo ; Oike, Yuichi ; Ishida, Susumu. / Eicosapentaenoic acid is anti-inflammatory in preventing choroidal neovascularization in mice. In: Investigative Ophthalmology and Visual Science. 2007 ; Vol. 48, No. 9. pp. 4328-4334.
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T1 - Eicosapentaenoic acid is anti-inflammatory in preventing choroidal neovascularization in mice

AU - Koto, Takashi

AU - Nagai, Norihiro

AU - Mochimaru, Hiroshi

AU - Kurihara, Toshihide

AU - Izumi-Nagai, Kanako

AU - Satofuka, Shingo

AU - Shinoda, Hajime

AU - Noda, Kousuke

AU - Ozawa, Yoko

AU - Inoue, Makoto

AU - Tsubota, Kazuo

AU - Oike, Yuichi

AU - Ishida, Susumu

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N2 - PURPOSE. To investigate the role of eicosapentaenoic acid (EPA), the major ω-3 polyunsaturated fatty acid (PUFA), in the development of choroidal neovascularization (CNTV), 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, MCP1, 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.

AB - PURPOSE. To investigate the role of eicosapentaenoic acid (EPA), the major ω-3 polyunsaturated fatty acid (PUFA), in the development of choroidal neovascularization (CNTV), 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, MCP1, 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.

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