Anti-Inflammatory Effect of Eicosapentaenoic Acid on Diabetic Retina in vivo and Cytokine Expression in vitro

Abstract

Purpose:: Recently, leukocyte-mediated inflammation has been thought to develop the pathogenesis of diabetic retinopathy. The purpose of this study is to investigate the anti-inflammatory effect of eicosapentaenoic acid (EPA), one of ω-3 polyunsaturated fatty acids (PUFAs), on the retina of diabetic mice.

Methods:: Six-week-old C57BL/6 mice were fed with laboratory chow with or without 5% EPA for 2 weeks and experimental diabetes was induced by intraperitoneal injections of streptozotocin. Four weeks after induction of diabetes, leukocyte adhesion to the retinal vasculature was evaluated with a concanavalin A lectin perfusion-labeling technique. The expression and production of intercellular adhesion molecule (ICAM)-1 and monocyte chemotactic protein (MCP)-1 in TNF-α-stimulated b-End3 endothelial cells, and vascular endothelial growth factor (VEGF) and interleukin (IL)-6 in LPS-stimulated RAW264.7 macrophages were evaluated by RT-PCR and ELISA.

Results:: The number of adherent leukocytes to the retinal vasculature in EPA-fed diabetic mice (18.6 ± 5.1 cells per retina) was significantly fewer than control diabetic mice (11.9 ± 5.0). 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.

Conclusions:: EPA-rich diet resulted in significant suppression of diabetes-induced retinal inflammation in mice, possibly through downregulation of inflammatory molecules. These results suggest that frequent consumption of ω-3 PUFAs may prevent the development of diabetic retinopathy.

Keywords: diabetic retinopathy • inflammation • retina