Prospects: Dietary ω-3 polyunsaturated fatty acids, CCR2+ monocyte recruitment, and AMD?

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Abstract

Oxidative stress is thought to be an important player in the development of atrophic AMD. Chronic photo-oxidative stress induced phospholipid oxidation increases the expression of C-C motif chemokine 2 (CCL2), which is known to recruit CCR2+ monocyte in inflammatory process. Their possible role in promoting or inhibiting retinal degeneration is unknown. We show that atrophic AMD is associated with increased intraocular CCL2 levels and subretinal CCR2+ inflammatory monocyte infiltration in patients. Using age- and light-induced subretinal inflammation and photoreceptor degeneration in Cx3cr1 deficient mice, we show that genetic deletion of CCL2 or CCR2 and pharmacological inhibition of CCR2 prevents inflammatory monocyte recruitment, mononuclear phagocyte accumulation, and photoreceptor degeneration in vivo. Dietary ω-3 polyunsaturated fatty acids (PUFA) have been shown to inhibit CCL2 induction and inflammation in endotoxin-induced uveitis. They might represent a powerful tool for controlling inflammation and neurodegeneration in AMD.

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