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Aruna Gorusupudi, Fu-Yen Chang, Santosh Kumar Muddana, Gregory S Hageman, Paul S Bernstein; Significance of VLC-PUFAs in Diabetic Retinas Shown in Mouse and Human Donor Eyes. Invest. Ophthalmol. Vis. Sci. 2017;58(8):588.
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© ARVO (1962-2015); The Authors (2016-present)
A new class of non-dietary very long chain-polyunsaturated fatty acids (VLC-PUFAs), has been identified in the vertebrate retina. Defects of VLC-PUFA synthesis secondary to ELOVL4 mutations are associated with dominant Stargardt disease (STGD3), and we have previously shown that AMD affected eyes have significant changes in VLC-PUFA levels and n-3/n-6 ratios which are indicative of chronic inflammation.Fatty acid metabolism is greatly affected in hyperglycemia and dyslipidemia, which are the causative factors for diabetic retinopathy. Earlier studies have shown a decrease in LC-PUFAs in diabetic retinas. We hypothesize that VLC-PUFA levels and n-3/n-6 VLC-PUFA ratios are also affected in diabetic retinas.
In the present study, we analyzed fatty acids in human donor and mouse eyes. Human donor retinal punches and their respective sera were collected from the Utah Lions Eye Bank and used for fatty acid analysis. Heterozygous Ins2 (Akita) mice, which develop insulin dependent diabetes and control (WT) mice were used for this study. Mouse eyes were harvested, and 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 VLC-PUFA levels (%) in diabetic human retinas (n=7) (0.75 ± 0.11) were significantly lower in comparison to age-matched control donor retinas (n=21) (1.09 ± 0.2). The n-3/n-6 VLC-PUFA ratios were also decreased in diabetic human donor retinas (1.57 ± 0.1) in comparison to age-matched control donor retinas (1.77 ± 0.1). In the retinas of diabetic mice, the VLC-PUFA levels (0.786 ± 0.18) were reduced in comparison to WT mice (2.27 ± 0.05), and retinal n-3/n-6 VLC-PUFA ratios were reduced in diabetic mice (3.87 ± 0.5) relative to WT mice (8.99 ± 0.35).
The present study shows that diabetes leads to decreased serum n-3/n-6 LC-PUFA ratios, retinal n-3/n-6 VLC-PUFA ratios, and retinal VLC-PUFA levels, which in turn could promote retinopathy. Diet is known to play an important role in altering the levels and ratios of n-3/n-6 LC-PUFAs in serum which in turn influence the n3/n6 VLC-PUFA ratios and levels in retina with possible beneficial effects on macular physiology and protection against degeneration.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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