Vitamin B3, also known as niacin and nicotinic acid, prevents eye degeneration in glaucoma-prone mice, according to a study published in the Feb. 17 issue of the journal Science.
Williams et al show that dietary supplementation with a single molecule (vitamin B3 or NAM) or Nmnat1 gene therapy significantly reduces vulnerability to glaucoma by supporting mitochondrial health and metabolism. Image credit: Mizianitka.
Glaucoma, a group of complex, multifactorial diseases, is one of the most common neurodegenerative diseases worldwide and the most common cause of age-related blindness in the United States. There is currently no cure, and once vision is lost, the condition is irreversible.
In most glaucoma patients, harmfully high pressure inside the eye or intraocular pressure leads to the progressive dysfunction and loss of retinal ganglion cells (neuronal cells that connect the eye to the brain via the optic nerve).
Increasing age is a key risk factor for glaucoma, contributing to both harmful elevation of intraocular pressure and increased neuronal vulnerability to pressure-induced damage.
“We wanted to identify key age-related susceptibility factors that change with age in the eye and increase vulnerability to disease and in particular neuronal disease,” said Prof. Simon W.M. John, from the Jackson Laboratory, Tufts University of Medicine and the Howard Hughes Medical Institute.
“By understanding general age-related mechanism, there is the potential to develop new interventions to generally protect from common age-related disease processes in many people.”
Conducting a variety of genomic, metabolic, neurobiological and other tests in DBA/2J mice, a widely used model of chronic, age-related, inherited glaucoma, Prof. John and co-authors discovered that NAD — a molecule vital to energy metabolism in neurons and other cells — declines with age.
The decrease in NAD levels reduces the reliability of neurons’ energy metabolism, especially under stress such as increased intraocular pressure.
“Like taking that big hill on your old bike, some things are going to fail more often,” said Prof. John, corresponding author of the study.
“The amount of failure will increase over time, resulting in more damage and disease progression.”
In essence, the treatments of vitamin B3 boosted the metabolic reliability of aging retinal ganglion cells, keeping them healthier for longer.
“Because these cells are still healthy, and still metabolically robust, even when high intraocular pressure turns on, they better resist damaging processes,” said Dr. Pete Williams, first author of the study and a researcher at the Jackson Laboratory.
The researchers also found that a single gene-therapy application of Nmnat1 — the gene for an enzyme that makes NAD from nicotinamide — prevented glaucoma from developing in DBA/2J mice.
“It can be a problem for patients, especially the elderly, to take their drugs every day and in the correct dose. So gene therapy could be a one-shot, protective treatment,” Dr. Williams said.
“Gene therapies, through injections into the eye, have been approved for a handful of very rare, human genetic eye disorders, and their demonstration of an important age-dependent factor may enable gene therapy for more common eye disease.”
The authors are pursuing clinical partnerships to begin the process of testing the effectiveness of vitamin B3 treatment in glaucoma patients. They are also exploring potential applications for the treatment in other diseases involving neurodegeneration.
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Pete A. Williams et al. 2017. Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice. Science 355 (6326): 756-760; doi: 10.1126/science.aal0092
