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Retinal bioavailability and functional effects of a synthetic very-long-chain polyunsaturated fatty acid in mice.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Feb 09; Vol. 118 (6). - Publication Year :
- 2021
-
Abstract
- Rare, nondietary very-long-chain polyunsaturated fatty acids (VLC-PUFAs) are uniquely found in the retina and a few other vertebrate tissues. These special fatty acids play a clinically significant role in retinal degeneration and development, but their physiological and interventional research has been hampered because pure VLC-PUFAs are scarce. We hypothesize that if Stargardt-3 or age-related macular degeneration patients were to consume an adequate amount of VLC-PUFAs that could be directly used in the retina, it may be possible to bypass the steps of lipid elongation mediated by the retina's ELOVL4 enzyme and to delay or prevent degeneration. We report the synthesis of a VLC-PUFA (32:6 n-3) in sufficient quantity to study its bioavailability and functional benefits in the mouse retina. We acutely and chronically gavage fed wild-type mice and Elovl4 rod-cone conditional knockout mice this synthetic VLC-PUFA to understand its bioavailability and its role in visual function. VLC-PUFA-fed wild-type and Elovl4 conditional knockout mice show a significant increase in retinal VLC-PUFA levels in comparison to controls. The VLC-PUFA-fed mice also had improvement in the animals' visual acuity and electroretinography measurements. Further studies with synthetic VLC-PUFAs will continue to expand our understanding of the physiological roles of these unique retinal lipids, particularly with respect to their potential utility for the treatment and prevention of retinal degenerative diseases.<br />Competing Interests: Competing interest statement: A.G., R.R., J.D.R., P.S.B., and the University of Utah have filed a provisional patent application on the chemical synthesis of VLC-PUFAs and their therapeutic effects.
- Subjects :
- Animals
Biological Availability
Disease Models, Animal
Fatty Acids, Unsaturated genetics
Fatty Acids, Unsaturated pharmacology
Humans
Mice
Mice, Knockout
Retina pathology
Retinal Degeneration diet therapy
Retinal Degeneration genetics
Retinal Degeneration pathology
Visual Acuity genetics
Eye Proteins genetics
Fatty Acids, Unsaturated metabolism
Membrane Proteins genetics
Retina metabolism
Retinal Degeneration metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 118
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 33526677
- Full Text :
- https://doi.org/10.1073/pnas.2017739118