There is currently no cure for the group of eye diseases that make up glaucoma. However, new research points to a way of preventing the disease, as vitamin B-3 has been proven effective as a treatment in mice.

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New mouse study shows that treatment with vitamin B-3 is effective against glaucoma.

The research – led by Jackson Laboratory professor and Howard Hughes medical investigator Simon W.M. John – investigates the effect of vitamin B-3 on mice that had been genetically modified to be prone to developing glaucoma. The findings were published in the journal Science.

Glaucoma is the name given to a group of neurodegenerative diseases that affect the optic nerve and may lead to visual impairment and blindness. In the so-called open-angle glaucoma, a buildup of fluid inside the eye raises the intraocular pressure to a point where it damages the optic nerve, eventually causing the loss of retinal ganglion cells. These are neuronal cells that connect the eye to the brain through the optic nerve.

The condition reportedly affects more than 60 million people worldwide, with 3 million cases of glaucoma suspected in adults in the United States.

Advanced age is a risk factor for glaucoma, as its prevalence increases with age and the optical nerve, along with the neuronal cells, become more vulnerable to the harmful effects of intraocular pressure.

Prof. John and colleagues carried out a set of genetic, metabolic, and neurobiological tests in a group of mice that were genetically predisposed to developing glaucoma, as well as in a healthy control group.

The researchers found that the nicotinamide adenine dinucleotide (NAD) molecule decreases with age. NAD is a coenzyme that plays a key role in the oxidation of a cell. A healthy body produces its own reduced NAD with the help of vitamin B-3. When ingested, vitamin B-3 eventually converts into NAD.

The decline in NAD weakens the metabolism of the brain cells, and intraocular pressure is particularly dangerous in the context of a NAD-deprived body.

Prof. John explains the mechanism using an analogy:

There is an analogy with an old motorbike. It runs just fine, but little things get less reliable with age. One day you stress it: you drive it up a steep hill or you go on a really long journey, and you get in trouble. It is less reliable than a new bike, and it is going to fail with a higher frequency than that new bike. Like taking that big hill on your old bike, some things are going to fail more often. The amount of failure will increase over time, resulting in more damage and disease progression.”

The researchers added B-3 to the drinking water of glaucoma-predisposed mice. This canceled most molecular changes usually associated with advancing age and protected against the onset of glaucoma.

According to the authors, this suggests that treatments with vitamin B-3 – also known as niacin, or nicotinamide – improves the metabolism of aging retinal ganglion cells, keeping them healthy. The fact that they are healthier and more robust for a longer period of time makes them more resilient to the pressure-induced damage.

Additionally, the scientists found that an insertion of the Nmnat1 gene into the body of genetically predisposed mice stopped glaucoma from developing. The Nmnat1 gene is responsible for the enzyme that forms NAD from vitamin B-3.

Gene therapy refers to a range of experimental techniques, including replacing mutated genes with healthy replicas, knocking out disease-causing genes, and inserting new genes into the body in order to stop a disease.

Postdoctoral associate at the Jackson Laboratory and first author of the study, Pete Williams, explains the benefits of using gene therapy in treating glaucoma:

“It can be a problem for patients, especially the elderly, to take their drugs every day and in the correct dose,” Williams says. “So gene therapy could be a one-shot, protective treatment.”

Wiliams also points out that gene therapy has been previously used to treat very rare genetic eye disorders. However, he hopes that the focus on age-related factors brought about by their study would make gene therapy available for common eye diseases.

Prof. John and his team are currently working on closing clinical partnerships to test how effective a B-3 treatment would be in other neurodegenerative diseases.

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