title: Vitamin B3modulates mitochondrial vulnerability and prevents glaucoma in aged mice.
abstract: Glaucomas are neurodegenerative diseases that cause vision loss, especially in the elderly. The mechanisms initiating glaucoma and driving neuronal vulnerability during normal aging are unknown. Studying glaucoma-prone mice, we show that mitochondrial abnormalities are an early driver of neuronal dysfunction, occurring before detectable degeneration. Retinal levels of nicotinamide adenine dinucleotide (NAD+, a key molecule in energy and redox metabolism) decrease with age and render aging neurons vulnerable to disease-related insults. Oral administration of the NAD+precursor nicotinamide (vitamin B3), and/or gene therapy (driving expression ofNmnat1, a key NAD+-producing enzyme), was protective both prophylactically and as an intervention. At the highest dose tested, 93% of eyes did not develop glaucoma. This supports therapeutic use of vitamin B3in glaucoma and potentially other age-related neurodegenerations.
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA.
authors.forename: Pete A
authors.identifier: 0000-0001-6194-8397
authors.initials: PA
authors.lastname: Williams
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA.
authors.forename: Jeffrey M
authors.identifier: 0000-0003-3832-3553
authors.initials: JM
authors.lastname: Harder
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA.
authors.forename: Nicole E
authors.identifier: 0000-0001-6068-940X
authors.initials: NE
authors.lastname: Foxworth
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA.
authors.forename: Kelly E
authors.identifier: 0000-0002-0368-6218
authors.initials: KE
authors.lastname: Cochran
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA.
authors.forename: Vivek M
authors.identifier: 0000-0001-5126-707X
authors.initials: VM
authors.lastname: Philip
authors.affiliation: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Vittorio
authors.identifier: 0000-0002-1592-3532
authors.initials: V
authors.lastname: Porciatti
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Oliver
authors.identifier: 0000-0002-4934-3931
authors.initials: O
authors.lastname: Smithies
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA. simon.john@jax.org.|Department of Ophthalmology, Tufts University of Medicine, Boston, MA 02111, USA.|The Howard Hughes Medical Institute, Bar Harbor, ME 04609, USA.
authors.forename: Simon W M
authors.identifier: 0000-0002-4319-0356
authors.initials: SW
authors.lastname: John
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D016922:Cellular Senescence; D015316:Genetic Therapy; D005901:Glaucoma / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D009243:NAD / Q000172:deficiency*; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000517:prevention & control*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009536:Niacinamide / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000235:genetics; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D009243:NAD; D009536:Niacinamide; D009612:Nicotinamide-Nucleotide Adenylyltransferase; C510972:Nmnat1 protein, mouse