Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice

Pete A. Williams, Jeffrey M. Harder, Nicole E. Foxworth, Kelly E. Cochran, Vivek M. Philip, Vittorio Porciatti, Oliver Smithies, Simon W M John

Research output: Contribution to journalArticle

126 Scopus citations

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 of Nmnat1, 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 B3 in glaucoma and potentially other age-related neurodegenerations.

Original languageEnglish (US)
Pages (from-to)756-760
Number of pages5
JournalScience
Volume355
Issue number6326
DOIs
StatePublished - Feb 17 2017

ASJC Scopus subject areas

  • Medicine(all)
  • General

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    Williams, P. A., Harder, J. M., Foxworth, N. E., Cochran, K. E., Philip, V. M., Porciatti, V., Smithies, O., & John, S. W. M. (2017). Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice. Science, 355(6326), 756-760. https://doi.org/10.1126/science.aal0092