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The Ophthalmologist / Issues / 2018 / Oct / Animal Instincts
Research & Innovations Retina

Animal Instincts

A study into the retinal membranes of rodents attempts to shed light on autosomal dominant Stargardt disease and age-related macular degeneration

By Phoebe Harkin 10/24/2018 1 min read

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Stargardt-like macular dystrophy is an inherited disease caused by a mutation in the gene controlling the synthesis of certain polyunsaturated fatty acids (PUFAs). The disease (caused by a mutations of the elongation of very-long-chain fatty acids-4 –or ELOVL4 gene) mainly affects the cone-photoreceptor-rich macula of the eye and results in a loss of central vision – but a question remains: why are rod cells in the peripheral retina – which also require PUFAs for normal signaling – not affected? With the help of a few furry friends, a team from the University of Oklahoma Health Sciences Center tried to find (part of) the answer.

The researchers, led by Martin-Paul Agbaga, performed comprehensive glycerophospholipid analyses to ascertain the differences in fatty acid makeup between rod-rich retinas from nocturnal mice, and cone-cell rich retinas from diurnal animals – in this case, 13 lined ground squirrels, tree squirrels, and tree shrews. The team hypothesized that different PUFA profiles in rod and cone cells could account for their different responses to disease.

The results showed that the membranes of rod-dominant animals had higher levels of long-chain (LC)-PUFAs and very-long-chain (VLC)-PUFAs compared with cone-dominant animals, as well as two-fold higher levels of di-DHA molecular species of glycerophospholipids.

“Our studies confirmed previous research, which highlights significant differences in DHA and VLC-PUFA found in the cone-photoreceptor-rich macula of the human eye relative to the peripheral retina. But our data also show that cone photoreceptors intrinsically have low levels of DHA and VLC-PUFA, which could be due to differences in their metabolic and functional requirements,” says Agbaga. “We believe mutations or other factors that cause further decrease in the already low levels of DHA and VLC-PUFA in the cone photoreceptors contribute to disease pathology. In the case of Stargardt-like patients, as ELOVL4 is not involved in DHA biosynthesis, it implies that dietary supplementation of DHA will not be beneficial to them; rather, it is possible that supplying VLC-PUFA could be the best therapeutic approach.”

References

  1. M Agbaga et al., “Differential composition of DHA and very-long-chain PUFAs in rod and cone photoreceptors”, Journal of Lipid Research, 59, 1586-1596 (2018). PMID: 29986998.

About the Author(s)

Phoebe Harkin

I’ve always loved telling stories. So much so, I decided to make a job of it. I finished a Masters in Magazine Journalism and spent three years working as a creative copywriter before itchy feet sent me (back)packing. It took seven months and 13 countries, but I’m now happily settled on The Ophthalmologist, where I’m busy getting stuck into all things eyeballs.

More Articles by Phoebe Harkin

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