Synthesized very-long-chain polyunsaturated fatty acids improves retinal function in mice

Scientists at the University of Utah have developed a method for synthesizing large enough quantities of very-long-chain polyunsaturated fatty acids (VLC-PUFAs) to evaluate their potential sight-preserving properties.

This special class of lipids, or fatty acids, found in the retina of the eye and in just a few other parts of the body play an important role in maintaining vision.

In a news release, investigators noted that it has been difficult to study whether

giving VLC-PUFAs to patients as a supplement could prevent blinding eye diseases like age-related macular degeneration, diabetic retinopathy, and some inherited retinal diseases. Investigators noted that VLC-PUFAs are made in the body by the ELOVL4 enzyme but are rarely consumed as part of a normal diet, and weren’t commercially available in enough quantities for animal or human research.

According to the release, the John A. Moran Eye Center’s Paul S. Bernstein, MD, PhD, and colleagues from the University of Utah’s Chemistry Department have changed the paradigm, inventing a method for synthesizing large enough quantities of VLC-PUFAs to evaluate their potential sight-preserving properties.

The method and the results of the first study to use it were published in Proceedings of the National Academy of Sciences of the United States of America (PNAS).¹

Bernstein is Moran’s vice-chair for clinical and basic science research and the Val A. and Edith D. Green Presidential Professor of Ophthalmology and Visual Sciences.

Bernstein’s laboratory focuses on the biochemistry and biophysics of nutritional interventions against inherited and acquired ocular disorders. He helped develop the protective AREDS2 supplement formulation for patients with age-related macular degeneration.

Investigators noted in the release that the study determined that VLC-PUFA supplementation increased levels of the lipids in the retina and also improved visual function in normal mice and in mice with a defect in the ELOVL4 enzyme.

While Bernstein said in the release that there is more work to be done, the results are a promising first step.

“Synthesizing VLC-PUFAs opens up a whole new area of study, and these first results are very promising,” Bernstein, the paper’s corresponding author, said in a statement. “Our results raise interesting questions about how orally administered VLC-PUFAs improve vision, how they are carried in the bloodstream, and how they are selectively targeted to the retina. The VLC-PUFA formulation, dosage, and timing of the intervention first need to be optimized, and then the underlying mechanisms will need to be defined.”

Organic Chemistry Professor John D. Rainier, PhD, a co-author on the research, said in a statement that the group is confident it can synthesize additional VLC-PUFA variants.

“There are a number of VLC-PUFA variants that are present in the human eye,” he said in a release. “So far we have only made one member of this family, but we are confident that our new synthetic method will enable us to both synthesize and study the other variants and by doing that get a much better idea of what it is that each of the individual VLC-PUFAs do.”

Additional authors on the PNAS study were Aruna Gorusupudi, Rameshu Rallabandi, Binxing Li, Ranganathan Arunkumar, J. David Blount, Gergory T. Rognon, Fu-Yen Chang, Alexander Wade, Steven Lucas, and John C. Conboy.

According to the release, the study was supported by a Knights Templar Career Starter Grant, a University of Utah Center on Aging Seed Grant, a Foundation Fighting Blindness Grant, a Carl Marshall Reeves and Mildred Almen Reeves Foundation Grant, and departmental core grants from Research to Prevent Blindness and the National Institutes of Health.

Reference

1. Paul S. Bernstein, MD, PhD, et al. Retinal Bioavailabilty and Functional Effects of a Synthetic Very-Long-Chain Polyunsaturated Fatty Acid in Mice; Proceedings of the National Academy of Sciences of the United States of America; https://doi.org/10.1073/pnas.2017739118