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A. Higuchi, K. M. Connor, C. M. Aderman, J. Chen, J. P. SanGiovanni, N. N. Salem, Jr., E. Y. Chew, S. Majchrzak, L. E. H. Smith; Omega-3 Long-Chain Polyunsaturated Fatty Acids (LCPUFAs) Suppress Retinal COX-2 mRNA and Retinal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3416.
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Lipid based molecules act as effectors of angiogenesis and inflammation; among the most potent are the eicosanoids, derived from the 20 carbon long chain polyunsaturated fatty acids (LCPUFAs), through the cyclooxygenase (COX) and lipoxygenase (LOX) pathways. Retinal expression of COX and LOX is both constitutive and inducible. COX-2 inhibition is protective against retinopathy. Omega-3 LCPUFAs exhibit anti-inflammatory properties. We have found that dietary intake of ω-3 LCPUFAs suppresses proliferative retinopathy in a mouse model of oxygen-induced retinopathy (OIR). Here we demonstrate that ω-3 LCPUFAs may inhibit pathologic neovascularization through suppression of COX-2 mRNA in this same model.
C57Bl/6 mothers were fed (from postnatal day 0 (P0)) a diet enriched with ω-3 LCPUFA or a diet elevated in ω-6 LCPUFA. LCPUFA composition of the mother’s diet was reflected in the milk. The change in ω-6/ω-3 ratio was also reflected in retina of the pups. To induce retinopathy the mothers and pups were placed in 75% oxygen for 5 days from postnatal day 7 (P7) to P12 and then returned to room air. Retinas were isolated at P8 and P14. Retinas were pooled across dietary groups, RNA was isolated, and converted to cDNA. Retinal COX-2 mRNA expression was compared to cyclophilin and quantified using real time-PCR.
An ω-3 LCPUFA diet versus an ω-6 LCPUFA diet was associated with a 40% inhibition of retinal neovascularization in the OIR mouse model at P17. In ω-3 fed versus ω-6 fed mice in the OIR model there was a 10 fold reduction of COX-2 mRNA at P8 and a 5 fold reduction of COX-2 mRNA at P14. Thus retinal COX-2 mRNA expression with ω-3 LCPUFA intake was significantly suppressed at P8 and P14 when compared to ω-6 LCPUFA intake.
This finding suggests that an ω-3 LCPUFA diet may inhibit retinal neovascularization in part through altering COX-2 mRNA levels.
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