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R.E. Martin, R.S. Brush, S.J. Fliesler, S.A. Hopkins, I. Ranchon, R.E. Anderson; Characterization of Lipid Abnormalities in Photoreceptor Outer Segments of P23H and S334ter Transgenic Rats . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3547.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The rate of retinal degeneration in transgenic rats with P23H and S334ter rhodopsin mutations is not affected when photoreceptor rod outer segment (ROS) levels of docosahexaenoic acid (DHA) are manipulated by dietary supplementation, even though the transgenic animals maintain lower ROS DHA levels than the wild-type (WT) rats. We sought to determine: 1) Could these transgenes also change ROS cholesterol content, and 2) Can the DHA lost from ROS be attributed to a specific glycerolipid class? Methods: WT female Harlan SD/CD rats were bred with homozygous P23H or S344ter transgenic SD/CD rats. From embryonic day 15, dams were fed isocaloric (7% fat) semisynthetic diets made with safflower oil (SO) or flaxseed oil (FO), n-6/n-3 ratios of 189 and 0.4, respectively. Pups were maintained on these diets in dim (5-10 lux) cyclic light (12L:12D). Fatty acid (FA) profiles were determined by gas chromatography after lipid separation by thin-layer chromatography. Cholesterol (Chol) content and synthesis after intraocular [3H]acetate injection were determined by reverse-phase, radio-HPLC. Multivariant ANOVA with post-hoc Neuman-Keuls tests determined statistical significance (p<0.05; n∃5; 1 litter/n). Results: The relative masses of phosphatidylserine (PS), phosphatidylcholine (PC), and phosphatidylethanolamine (PE) were not changed by diet or mutation. There was enrichment of arachidonic acid in PE and of oleic acid in PS and PC in the transgenic rats. DHA enrichment in transgenic rats fed FO, but not SO, was reduced in PS, PC, and PE. Chol/FA ratios were elevated in the ROS of transgenic rats, although cholesterol synthesis was not sensitive to the transgenes. Conclusions: Decreased DHA in ROS of FO-fed rats with P32H and S334ter rhodopsin mutations is due to reduced DHA levels in PS, PC, and PE, rather than to changes in the relative abundance of these phospholipids. Increased Chol/FA ratios in the transgenic rats, relative to WT rats, are not related to retinal Chol synthesis.
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