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W.J. Esselman, W. Chen, T.S. Kern, D.B. Jump, J.V. Busik; Pro–inflammatory Changes in Blood Plasma and Retinal Fatty Acid Profiles in Streptozotocin (STZ) Diabetic Rats . Invest. Ophthalmol. Vis. Sci. 2005;46(13):398.
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Purpose: Microvascular damage in early–stage diabetic retinopathy is associated with low–grade chronic inflammatory condition. We have previously demonstrated that n6 fatty acids (linoleic18:2n6 and arachidonic20:4n6 ) have a pro–inflammatory effect, and the major n3 polyunsaturated fatty acid (PUFA) in the retina [docosahexaenoic acid (DHA22:6n3)] has a pronounced anti–inflammatory effect in retinal vascular endothelial cells. The retina has a unique fatty acid profile with one of the highest levels of long chain PUFA (especially arachidonic20:4n6 and DHA22:6n3) in the body. A disturbance of lipid metabolism in diabetes with a decrease in long chain PUFA is of particular importance in the retina, however, the experimental data on the diabetes–induced changes in retinal fatty acid profiles are very sparse. The purpose of this study was to determine retinal fatty acid profiles in diabetes. Methods: Male Sprague–Dawley rats were made diabetic with a single intraperitoneal injection of 65 mg STZ per kg body weight. At 2 weeks after STZ injection samples of blood were taken and at 12–16 weeks the animals were sacrificed and samples of blood and retinas were taken for determination of fatty acid profiles by RP–HPLC followed by UV and evaporative light scatter detection. Results: There was a 1.5 fold increase in total saponified fatty acids in plasma of diabetic vs. control animals. Moreover, the ratio of arachidonic20:4n6 acid relative to it's precursor, linoleic18:2n6 acid, and the ratio of DHA22:6n3 to it's precursor, α–linolenic18:3n3 acid were decreased in the plasma diabetic animals consistent with inhibition of Δ–5 and Δ–6 desaturases in diabetes. As a result of these changes the % of DHA22:6n3 in total plasma fatty acids decreased 1.4 times. In agreement with other studies, retinal profiles were very rich in DHA22:6n3 and arachidonic20:4n6 acid. Compared to controls the retinas of diabetic animals had 29% less DHA22:6n3 that led to 1.5 fold increase in n6–to–n3 ratio. Conclusions: This study demonstrates that retinas of diabetic animals have significant changes in fatty acid profile with an increase in n6–to–n3 ratio that may contribute to a pro–inflammatory state.
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