Year of the bull: UND researchers and their international colleagues find a link between taurine and inherited retinal dystrophies

“This is the thing many scientists wish for but rarely find,” smiles Keith Henry, Ph.D., from his office in the UND School of Medicine & Health Sciences (SMHS). “That direct link to treatment and making a difference immediately in the lives of others.”

With genuine excitement at the thought that his team may have made a life-changing discovery for children suffering from any number of congenital retinal neuropathies, Henry shook his head in disbelief at the suggestion that researchers at UND may have just figured out how to prevent, and maybe even stop, some progressive eye diseases.

That, at least, is the conclusion that Henry and a team of researchers – including UND graduate student Michael Allen and research specialist Madhur Shetty, M.S., and the lab of Professor Carlo Rivolta, Ph.D., head of the Ophthalmic Genetics Group at the University of Basel – reached in the paper they published recently in the American Medical Association-affiliated medical journal JAMA Ophthalmology.

“That’s one of the reasons this is so exciting,” says Henry, associate professor of biomedical sciences at North Dakota’s only interprofessional medical and health sciences school. “The possibility of impacting a person’s vision and their quality of life because of what we do in the lab — it puts a fire under you like few things do.”

How the eye works

Most of us learned in high school that eyes work by translating light into electrical signals for the brain to interpret. These signals communicate color, depth, shape, and movement, telling us what is “happening” immediately in front of us at any given time.

Here’s how it works: As light passes through an eye’s cornea, pupil, and lens to the back of the eye, it eventually hits the retina, a light-sensitive multilayered “film” opposite the lens that contains nerves called photoreceptors. These photoreceptors are categorized as either “rods” or “cones,” both of which help transform light and movement into information – the electrical signals the brain decodes and then acts upon in real time to give us sight.

Of course, light is also a constant insult to the eye. “We have these light-sensing discs in the rods and cones, and they’re getting bombarded all the time,” Henry says.

This bombardment by radiation creates free radicals that can damage the retina. To combat this damage, the discs are constantly being shed and absorbed by an adjacent layer of cells called the retinal pigment epithelium (RPE). This “dark” layer of RPE cells lies between the eyes’ photoreceptors and the vasculature, which extracts nutrients and amino acids from the blood and shuttles them to the rods and cones to ensure proper function.

With progressive retinopathies, though, this microscopic clean-up process misfires, resulting in a build-up of damaged discs and a harmful lack of raw materials the eye needs for both repair and function. The consequences of this misfire, over time, include hypersensitivity to light, cataracts, and total blindness when photoreceptors cease functioning.

Along these lines, inherited retinal dystrophies, including Leber congenital amaurosis (LCA) and early-onset retinal dystrophy (EORD), are genetic conditions that usually lead to progressive vision loss, particularly in children. Typically diagnosed before age five, these specific conditions are caused by mutations in more than 500 genes, making the development of broadly effective treatments extraordinarily difficult.

El toro

So it is that Henry and his international team of researchers are hoping that their work may open the door for treating some of these catastrophic outcomes.

Enter taurine. First identified in the bile of an ox bull, taurine is a naturally occurring sulfur-containing amino acid and a strong antioxidant that while not contributing to the building of proteins is abundant in human tissues and cells. Because humans can synthesize taurine at low levels, and because taurine is widely available in meats and seafood, the amino acid is generally classified as “conditionally” essential rather than strictly essential, meaning it has no recommended daily intake level.

Henry’s research suggests health providers may want to pay closer attention to taurine levels in individuals who may harbor gene variants that lower their taurine.

“We’ve clearly shown the relationship between dysfunction of the taurine transporter and retinal dystrophy,” he says, “and shown at least in a limited study that we can raise plasma levels of taurine in some affected individuals through dietary taurine supplementation. This supplementation helps shunt taurine into the retina and was able to halt retinal degeneration.”

The line bears repeating: Henry’s team was able to halt retinal degeneration.

As he explains, plasma in the eye’s vasculature contains taurine, which floats around in a substance called the choroid and is adjacent to the retina attached to the RPE. To get into the photoreceptor cells and perform its job, though, taurine requires a transporter known as TauT.

“TauT is what we call a secondary active transporter, because it harnesses the energy stored in sodium gradients to energetically extract taurine out of the bloodstream and concentrate it inside the RPE cells at the back of the eye, where it can then be distributed into the other layers of the retina,” explains Henry. “From there, taurine moves into the rods and cones, where its antioxidant activity keeps the photoreceptor membranes healthy and supports the health of the other cells in the retina that ultimately feed into the optic nerve.”

But persons with a genetic variant that disrupts the ability of TauT to deliver taurine to the rods and cones risk damage to these vital cells. In time, these genetic changes appear to cause significant or complete loss of taurine transport into the RPE, resulting in cell death and eventual vision loss.

So how do these genetic variants cause TauT dysfunction? Is it because TauT can no longer recognize taurine and/or the transporter can no longer pull taurine into the cell? Is a variant causing TauT to fold incorrectly such that it gets moved into the cell’s own trash can by accident? Is it a mix of these things where some TauT gets to the surface, but it’s not very functional and some of it is getting shuttled to the trash?

Yes, yes, and yes, answers Henry, pausing to add that taurine transport and the severity of the retinal dystrophy in question all depend on the affected person’s genes – the SLC6A6 gene in particular.

“That’s why this shuttling is so important, and you have to get taurine out of the plasma and into the retinal layers that need it,” he says. “But it’s not only the retina. Our published studies found that TauT dysfunction usually coincided with heart problems – virtually all the patients affected by these variants exhibited one or more cardiomyopathies. Excitingly, the two individuals treated with taurine supplementation saw a complete reversal of their cardiomyopathies. But more research is needed to identify the mechanistic connection.”

Over the counter

Cautioning that his research team and its affiliates around the globe have a lot of work ahead of them, Henry says that next steps include “looking for the intermediaries – the things that regulate, control, and sort” not only taurine but other nutrients, amino acids, and genes involved in eyesight.

Still, he’s proud that his team was able to demonstrate that a treatment – if not cure – for some forms of EORD or LCA might be down the street at your local grocery or health food store. Taurine can already be purchased over-the-counter as a nutritional supplement and is commonly paired with caffeine and a variety of B vitamins in many so-called “energy” drinks.

“If taurine supplementation turns out to be effective, as our preliminary data suggests it can be,” Henry continues, adding that maybe EORD will be something health providers can screen for in children at birth, “maybe retinal degeneration never comes into play, maybe the cardiomyopathies and other physiological abnormalities never develop.”

All because a simple amino acid supplement prevents them.

Citing recent studies on taurine’s impact on other degenerative conditions like arthritis and aging, Henry confesses to at least considering visiting his health food store on the way home from the lab these days. “I’ve seriously thought about (supplementing),” he laughs, adding that he does not advocate consuming any supplements without physician oversight. “Who knows, maybe its use could actually help aging and vision long term by enhancing the ability of the eye to get rid of these radicals that are created by light.”

But he’s careful not to react too quickly – much more research is needed, he says, including clinical trials.

“Still, knowing that there’s something so simple that could profoundly change someone’s entire life. . .” he trails off. “We are so lucky all of this came together and I’m hoping we can carry this luck to those affected by these disorders.”