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

doi:10.1167/iovs.06-1148

Cited by 67 publications

(47 citation statements)

References 54 publications

(45 reference statements)

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“…29 Moreover, a PPAR␥ antagonist GW9662 has reversed EPA-induced inhibition of ICAM-1 mRNA expression in endothelial cells in vitro. 21 However, we found that GW9662 fails to reverse the EPA-induced inhibition of monocyte adhesion in the in vitro adhesion assay system (unpublished data Yamada H, Yoshida M, Ogawa Y, 2008). On the other hand, Arita et al demonstrated that resolvinE1, an endogenous lipid mediator derived from EPA, exerts an antiinflammatory effect through interaction with leukotriene B4 receptor BLT1 and chemerin receptor ChemR23.…”

Section: Discussionmentioning

confidence: 84%

Section: Effect Of Epa On Lps-induced Monocyte Adhesion To Aortic Endmentioning

confidence: 89%

“…In this study, serum EPA concentrations in EPA-treated and control groups were consistent with previous reports (supplemental Figure IIA). 20,21 Serum TG concentrations tended to be decreased by EPA treatment, although not statistically significant (supplemental Figure IIB and IIC).Confocal microscopic analysis of the aortic endothelium revealed that endothelial surface expression of VCAM-1 is significantly increased in LPS-treated mice relative to vehicle-treated mice (PϽ0.01; Figure 2), which is significantly inhibited by EPA treatment (PϽ0.01; Figure 2). …”

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confidence: 93%

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In Vivo and In Vitro Inhibition of Monocyte Adhesion to Endothelial Cells and Endothelial Adhesion Molecules by Eicosapentaenoic Acid

Yamada¹,

Yoshida²,

Nakano³

et al. 2008

ATVB

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Objective-A large-scale, prospective, randomized clinical trial has recently revealed that the addition of highly purified eicosapentaenoic acid (EPA) to low-dose statin therapy significantly reduces the incidence of major coronary events. Here we investigated in vivo and in vitro effect of EPA on monocyte adhesion to endothelial cells and adhesion molecules. Methods and Results-A new en face immunohistochemistry of endothelial surface in combination with confocal microscopy revealed marked reduction of lipopolysaccharide (LPS)-induced monocyte adhesion to the aortic endothelium in parallel with the suppression of vascular cell adhesion molecule 1 (VCAM-1) and nuclear translocation of nuclear factor-B p65 in EPA-treated mice relative to vehicle-treated groups. In an in vitro adhesion assay system under physiological flow conditions, EPA inhibited LPS-induced monocyte adhesion and endothelial adhesion molecules. We found significant decrease in plasma concentrations of soluble intercellular adhesion molecule 1 (sICAM-1) and sVCAM-1 in patients with the metabolic syndrome after a 3-month administration of highly purified EPA (1.8 g daily). Multivariate regression analysis revealed that EPA administration is the only independent determinant of sICAM-1 and sVCAM-1. O besity may be viewed as a state of chronic low-grade inflammation and confers a higher risk of atherosclerotic diseases. 1 There is considerable evidence that obese adipose tissue is markedly infiltrated by macrophages, 2,3 suggesting that they may participate in the inflammatory pathways that are activated in obese adipose tissue. Using an in vitro coculture system composed of adipocytes and macrophages, we have demonstrated that saturated fatty acids released from adipocytes via the macrophage-induced lipolysis serve as a naturally occurring ligand for Toll-like receptor 4 (TLR4) to induce the inflammatory changes in macrophages through nuclear factor-B (NF-B) activation. 4,5 Notably, n-3 polyunsaturated fatty acids (n-3 PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid are unable to activate macrophages and can even antagonize the proinflammatory effect of saturated fatty acids or LPS, 6 a well-defined exogenous ligand for TLR4, 7 thereby highlighting the antiinflammatory effect of n-3 PUFAs. Conclusions-ThisAtherosclerosis is a complex pathological process that is associated with vascular wall dysfunction and inflammation. 8The monocyte-endothelial cell interaction may play a crucial role in atherosclerotic plaque formation. 9 Indeed, the adhesion of circulating monocytes to the intimal endothelial cell monolayer is thought to be one of the earliest events, which is mediated through complex interactions among multiple adhesion molecules and their counterreceptors expressed by both endothelial cells and monocytes, such as selectins, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and ␤1-and ␤2-integrins. 10 Several previous reports indicated that the TLR4/NF-B signaling pathway in both endo...

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Section: Discussionmentioning

confidence: 84%

Section: Effect Of Epa On Lps-induced Monocyte Adhesion To Aortic Endmentioning

confidence: 89%

mentioning

confidence: 93%

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In Vivo and In Vitro Inhibition of Monocyte Adhesion to Endothelial Cells and Endothelial Adhesion Molecules by Eicosapentaenoic Acid

Yamada¹,

Yoshida²,

Nakano³

et al. 2008

ATVB

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“…As the primary FA in the retina, DHA helps regenerate rhodopsin, thereby reducing oxidative stress. Koto et al (136) suggested that an EPA-rich diet resulted in significant suppression of neovascularization, although some studies reported no such relation (127). Studies from our laboratory indicate that serum and retinal EPA:arachidonic acid and n-3:n-6 LC-PUFA ratios were significantly lower in AMD donor eyes than they were in age-matched control subjects (137).…”

Section: Introductionmentioning

confidence: 73%

The Age-Related Eye Disease 2 Study: Micronutrients in the Treatment of Macular Degeneration

Gorusupudi

Nelson

Bernstein

2017

Advances in Nutrition

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Age-related macular degeneration (AMD) is one of the leading causes of vision loss in the elderly. With an increasingly aged population worldwide, the need for the prevention of AMD is rising. Multiple studies investigating AMD with the use of animal models and cell culture have identified oxidative stress-related retinal damage as an important contributing factor. In general, diet is an excellent source of the antioxidants, vitamins, and minerals necessary for healthy living; moreover, the general public is often receptive to recommendations made by physicians and health care workers regarding diet and supplements as a means of empowering themselves to avoid common and worrisome ailments such as AMD, which has made epidemiologists and clinicians enthusiastic about dietary intervention studies. A wide variety of nutrients, such as minerals, vitamins, v-3 (n-3) fatty acids, and various carotenoids, have been associated with reducing the risk of AMD. Initial results from the Age-Related Eye Disease Study (AREDS) indicated that supplementation with antioxidants (b-carotene and vitamins C and E) and zinc was associated with a reduced risk of AMD progression. The AREDS2 follow-up study, designed to improve upon the earlier formulation, tested the addition of lutein, zeaxanthin, and v-3 fatty acids. In this review, we examine the science behind the nutritional factors included in these interventional studies and the reasons for considering their inclusion to lower the rate of AMD progression. Adv Nutr 2017;8:40-53.

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“…DHA is the major polyunsaturated fatty acid found in retinal rod outer segments, and some epidemiologic studies suggest the role of DHA in the prevention of age-related macular degeneration and dry eye syndrome (DES) (3,10). Intake of EPA has been shown to prevent choroidal neovascularization and related inflammation in mice (5). Moreover, anthocyanins, contained in bilberry, and lutein are also known to be effective ingredients for maintaining eye health.…”

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confidence: 99%

Effects of dietary supplementation with a combination of fish oil, bilberry extract, and lutein on subjective symptoms of asthenopia in humans

Kawabata

Tsuji

2011

Biomed. Res.

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The aim of this study was to determine the effects of dietary supplementation with a combination of fish oil, bilberry extract, and lutein on subjective symptoms of asthenopia in humans by a double-blind, randomized, parallel-group, and placebo-controlled trial. In the Active group, eleven subjects ingested a supplement containing omega-3 fatty acid-rich fish oil (docosahexaenoic acid 783 mg/day, eicosapentaenoic acid 162 mg/day), bilberry extract (anthocyanidin 59 mg/day), and lutein (17.5 mg/day) in soft gel capsule form, every day for 4 weeks. In the Placebo group, nine subjects ingested placebo capsules. Before and after supplementation, subjects completed a questionnaire to determine their asthenopia symptoms and were also assessed for mental fatigue symptom by the visual analog scale (VAS) test. Asthenopia symptoms such as "stiff shoulder, low back pain", "frustration", "dry-eye", and "stuffy head" were improved in the Active group. Furthermore, a score of mental fatigue was improved after 4 weeks of supplementation, and no side effects were observed after the 4-week supplementation and a 2-week washout period in the Active group. These results suggest that dietary supplementation with the combination of omega-3 fatty acid-rich fish oil, bilberry extract, and lutein may safely improve subjective symptoms of asthenopia and mental fatigue in humans.

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Eicosapentaenoic Acid Is Anti-Inflammatory in Preventing Choroidal Neovascularization in Mice

Cited by 67 publications

References 54 publications

In Vivo and In Vitro Inhibition of Monocyte Adhesion to Endothelial Cells and Endothelial Adhesion Molecules by Eicosapentaenoic Acid

In Vivo and In Vitro Inhibition of Monocyte Adhesion to Endothelial Cells and Endothelial Adhesion Molecules by Eicosapentaenoic Acid

The Age-Related Eye Disease 2 Study: Micronutrients in the Treatment of Macular Degeneration

Effects of dietary supplementation with a combination of fish oil, bilberry extract, and lutein on subjective symptoms of asthenopia in humans

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