Eicosapentaenoic acid suppresses ocular inflammation in endotoxin-induced uveitis.
OBJECTIVE
To investigate the effect of eicosapentaenoic acid (EPA) on acute ocular inflammation in an animal model of endotoxin-induced uveitis (EIU).


METHODS
C57Bl/6 mice (6-week-old males) were orally treated with EPA at a dose of 50 mg/kg/day for 5 days. EIU was then induced in the animals by intraperitoneal injection of 160 microg lipopolysaccharide (LPS). Twenty-four hours after LPS injection, leukocyte adhesion to the retinal vasculature was evaluated by the concanavalin A lectin perfusion-labeling technique, and leukocyte infiltration into the vitreous cavity was quantified. Furthermore, the protein levels of monocyte chemotactic protein (MCP)-1, interleukin (IL)-6, intercellular adhesion molecule-1 and phospholyrated nuclear factor (NF)-kappaB p65 in the retina and retinal pigment epithelium (RPE)-choroid complex were examined by enzyme-linked immunosorbent assay (ELISA).


RESULTS
At 24 h after LPS injection, the EIU animals treated with oral EPA administration showed a significant decrease in leukocyte adhesion to the retinal vessels by 43.4% (p<0.01) and leukocyte infiltration into the vitreous cavity by 49.2% (p<0.05). In addition, EPA significantly reduced the protein levels of MCP-1 and IL-6 in the retina and the RPE-choroid complex. Furthermore, phosphorylation of NF-kappaB was suppressed by EPA treatment.


CONCLUSIONS
Our data suggest that EPA inhibits multiple inflammatory molecules in vivo. EPA may become a novel strategy in the prevention and/or treatment of ocular inflammatory diseases.
Suzuki
Misa
M
Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Noda
Kousuke
K
Kubota
Shunsuke
S
Hirasawa
Manabu
M
Ozawa
Yoko
Y
Tsubota
Kazuo
K
Mizuki
Nobuhisa
N
Ishida
Susumu
S
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002829:Choroid / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D004731:Endotoxins / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000150:complications* / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014605:Uveitis / Q000139:chemically induced / Q000150:complications* / Q000517:prevention & control*
D015815:Cell Adhesion Molecules; D004731:Endotoxins; D018836:Inflammation Mediators; D016328:NF-kappa B; D015118:Eicosapentaenoic Acid