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RE Martin, I Ranchon, RS Brush, CR Williamson, SA Hopkins, RE Anderson; Extreme Ratios of Dietary n-6/n3 Fatty Acids Do Not Affect Rates of Degeneration in Heterozygous P23H and S334ter Rat Models of Autosomal Dominant Inherited Retinal Degeneration . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1409.
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Purpose: Omega 3 (n-3) fatty acids are important in retinal development and function. ROS from transgenic rats with P23H and S334ter rhodopsin mutation have lower levels of 22:6n-3 than wild type (WT) animals. We tested the hypothesis that the rate of retinal degeneration could be affected by feeding a diet supplemented with n-3 fatty acids. Methods: WT female Harlan SD/CD rats were bred with homozygous P23H or S344ter transgenic SD/CD rats. At embryonic day 15, the dams were started on isocaloric (7% fat) semisynthetic diets made with either safflower or flaxseed oil (SO; FO; n-6/n-3 ratios of 189 and 0.4, respectively). The pups were maintained on these diets in dim (5-10 lux) cyclic light (12h on/off). At P30 and P50, retinal function was evaluated by electroretinography (ERG). Outer nuclear layer (ONL) thickness was determined histologically at P35 and P55, as were the profiles of fatty acids in plasma and photoreceptor outer segments (ROS). Multivariant analysis of variance with post-hoc Scheffé tests determined statistical significance (p≤0.05; n≥5; 1 litter/n). Results: Dietary n-6/n-3 ratios had a profound effect on plasma fatty acid content, and a subtle effect on the retinas. The n-6/n-3 ratios of plasma from WT rats were approximately 1.4 and 61.6 for the FO and SO diets, respectively, and 0.2 and 1.2 for the WT retinas. At P35, neither the S334ter nor the P23h had ERGs amplitudes significantly different from WT, although there was histologic evidence of degeneration in the S334ter rats. At P55, the S334ter rats tended to be most severely affected histologically, and they and P23H rats had diminished ERG responses relative to WT animals. The diets had no significant effect on the rate of degeneration. Conclusion: Although ROS of P32H and S334ter rats have lower 22:6n-3 levels than WT rats, dietary supplementation with n-3 precursors did not affect the rate of retinal degeneration in either group.
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