Injecting a fatty acid that is used to make very long fat molecules into the eyes of elderly mice improved their vision for up to a month, indicating that the natural compound could potentially be used to treat age-related vision conditions in humans.
The results, published in Science Translational Medicine on Sept. 24, “were shocking" to Dorota Skowronska-Krawczyk, Ph.D., a vision researcher at the University of California, Irvine and study lead.
“We were thinking we will have to add something else, but the supplementation of only this one fatty acid was already giving the result," she told Fierce Biotech.
That one fatty acid has a name that hardly rolls off the tongue: 24:5n-3, or tetracosapentaenoic acid (TPA). It’s a key precursor to the extremely long fatty acid molecules that are vital for vision, but Skowronska-Krawczyk’s team found that as mice age, the gene that makes it becomes less and less expressed. This confirms a link between the TPA gene, called ELOVL2, and eye aging in mice that the researchers previously identified in 2020.
In the new study, the researchers also analyzed genetic data from patients with age-related macular degeneration (AMD) and found that certain forms of ELOVL2 were associated with an earlier onset of the disease.
With TPA proving capable of restoring vision in mice, Skowronska-Krawczyk is now keen to test the approach in nonhuman primates and is also trying to determine whether the fatty acid can be given orally rather than through an eye injection. Meanwhile, a company she co-founded called Lucina Biotherapeutics is formulating the molecule for investigational new drug application-enabling studies.
“In a sense, we are closer than many other drugs, because it's a natural product,” Skowronska-Krawczyk said. If oral delivery proves effective, she thinks that TPA could serve as both a low-dose supplement that people take to stave off vision loss and a high-dose, targeted treatment for eye diseases like AMD.
Fatty acids, especially omega-3s like those found in fish oil, have long been associated with eye health. “Maybe eat a lot of fish before we come with the pill,” Skowronska-Krawczyk joked.
Most TPA is made in the liver, but the eye also makes its own supply because TPA is needed to produce docosahexaenoic acid (DHA) and very long-chain polyunsaturated fatty acids (VLC-PUFAs), which the eye depends on. Fatty acids are used in every single cell membrane, but rod cells in the retina in particular need those fatty acids to be very long so that their cell membranes are flexible, Skowronska-Krawczyk explained. Rhodopsin, the light-sensing protein of rod cells, needs a flexible membrane in order to function properly.
“This part of the photoreceptors is used up every day a little bit, because of the light and light damage, but also because of the visual cycle itself,” Skowronska-Krawczyk said. In order to regenerate these lost cells, the eye needs a constant supply of DHA and VLC-PUFAs; if there isn’t enough TPA to make those long fatty acids, as can happen with aging, the eye will have no choice but to settle for shorter fatty acids instead, impairing the ability of the photoreceptors to respond to light.
The idea to inject TPA into the eyes as a way to restore vision came from years of basic research into how the visual system works, Skowronska-Krawczyk said. In the current tough funding environment, she hopes her team’s breakthrough underscores the importance of supporting basic academic research.
“This is not only for us to play in the laboratory, but actually to bring something real to patients,” she said.