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Aruna Gorusupudi, Fu-Yen Chang, Paul S Bernstein; Supplementation with EPA and DHA to Improve VLC-PUFA Levels in Diabetic Mice. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5363.
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The main causative factors for diabetic retinopathy are hyperglycemia and dyslipidemia. Decreased serum n3/n6 ratios (omega-3 index) observed in diabetic patients are indicative of chronic inflammation and could be a contributing factor for diabetic retinopathy. EPA and DHA are not only biologically active molecules, but they also give rise to other biologically active molecules such as VLC-PUFAs (very long chain-polyunsaturated fatty acids) and neuroprotectins which can play a major role in pathological processes. VLC-PUFAs are a special class of fatty acids present only in the vertebrate retina, responsible for membrane fluidity in the photoreceptors. In a previous study, we observed a decrease in the serum n3/n6 ratio, retinal n3/n6 ratio and decreased VLC-PUFA levels in human donor tissues. We hypothesize that treatment with EPA and DHA could improve adiponectin levels as well as the retinal n3/n6 LC-PUFA ratio and VLC-PUFA levels, thereby slowing the process of degeneration. In this study, we fed n3 fatty acids to heterozygous Ins2Akita mice to observe the changes in serum n3/n6 ratio and retinal VLC-PUFA levels.
We supplemented Akita mice and WT (C57B6L) mice with EPA: DHA (2:1 v/v, 32g/kg/day) mixed with pellet diet for six weeks. Mice were sacrificed, and serum, liver, brain and eye tissues were harvested. Retinas were separated from RPE and used for VLC-PUFA analysis. Using a standardized method, fatty acid methyl esters were extracted and then analyzed by GC-MS (electron ionization mode). Two methods (A and B) were adopted; method A was used to analyze the LC-PUFAs, while method B was used to analyze C24- C36 VLC-PUFAs.
The EPA+DHA supplemented Akita mice had lower adiponectin levels when compared to control Akita mice. The serum and retinal n3/n6 LC-PUFA ratios also increased in the EPA+DHA supplemented group compared to control Akita mice. Akita mice, in general have a decreased level of VLC-PUFAs when compared to WT type mice. With supplementation, we observed an increase in VLC-PUFA levels in EPA+DHA group in comparison to control Akita mice, although not as great as supplemented WT mice.
Supplementation with EPA+DHA to diabetic mice leads to improvement in serum n3/n6 LC-PUFA ratios and VLC-PUFA levels. Further studies with spontaneous diabetic models will give a better understanding of the beneficial effects of n3 fatty acid supplementation on diabetic retinopathy.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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