POAG associated with lower plasmatic nicotinamide levels
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Primary open-angle glaucoma was found to be associated with lower plasmatic nicotinamide levels, and researchers suggest that the vitamin may have future therapeutic use.
“Mitochondrial dysfunctions and decreased NAD content are hallmarks of aging in most organs, and many experimental studies, essentially performed on mouse models, have revealed that strategies based on NAD repletion effectively reverse age-related phenotypes and disorders,” the authors wrote. “Recent studies on the DBA/2J mouse model of glaucoma have further conrmed a dose-dependent protective effect of NAD repletion on the optic nerve.”
Researchers conducted separate analyses on plasma from two cohorts, with the initial cohort consisting of 34 patients with primary open-angle glaucoma (POAG) and 30 glaucoma-free patients who were evaluated via a semiquantitative method. The replicative cohort, which consisted of 20 patients with POAG and 15 glaucoma-free patients, was evaluated using an independent quantitative method. Patients with POAG were included only if they showed IOP less than 21 mm Hg, while control subjects were required to have visual acuity greater than or equal to 20/50. Individuals with a family history of ocular hypertension, glaucoma or any other intraocular pathology were excluded from the control group.
The initial cohort showed a 36% average decrease in nicotinamide adenine dinucleotide (NAD) in patients with POAG compared with glaucoma-free patients, with median concentrations of NAD lower in patients with POAG (0.12 lM vs. 0.18 lM) overall. Patients with POAG in the replicative cohort also showed lower median NAD concentrations (0.14 lM vs. 0.21 lM). A 30% (P = .022%) reduction of median NAD concentration was observed in the initial cohort and a 33% reduction (P = .011) was observed in the replicative cohort. No correlation was observed between nicotinamide levels and age.
“Further studies with larger cohorts are also required, as well as investigations in populations with various cultural dietary habits, to nd out whether this deciency is consistently associated with POAG and eventually with other forms of glaucoma,” the researchers wrote. “Convergence between recent studies showing that oral administration of nicotinamide prevents glaucoma in the DBA/2J mouse model and our study on patients with POAG opens promising therapeutic perspectives based on nicotinamide supplementation.” – by Eamon Dreisbach
Disclosures: The authors report no relevant financial disclosures.
Perspective
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Derek MacDonald, OD, FAAO
The two strongest risk factors for OAG are advanced age and increased IOP, and at present only the latter is readily modifiable. Although it may be nice to turn back the clock, altering other age-dependent risk factors may be a means to a similar end.
Mitochondrial dysfunction plays a key role in a number of optic neuropathies and age-related neurodegenerative processes. Given that glaucoma is simultaneously the most common optic neuropathy and neurodegenerative disease worldwide, it’s no surprise that researchers have turned their attention to preventing or reversing mitochondrial vulnerability through the maintenance of an adequate “fuel supply” to satisfy the high metabolic demands of retinal ganglion cells (RGCs).
In demonstrating a greater than 30% reduction in plasma nicotinamide (vitamin B3) levels in individuals with OAG, the authors build on recent animal studies suggesting a protective role for supplemental nicotinamide through oral administration or gene therapy. In fact, nicotinamide not only afforded neuroprotection to RGCs challenged by elevated IOP, but concurrently decreased IOP, with a favorable tolerability and safety profile.
While still far from moving from bench to bedside, targeting age-related mitochondrial dysfunction is an exciting prospect in the treatment of glaucomatous (and other) optic neuropathies and other neurodegenerative diseases.
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