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 prior to 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 B
3
), and/or gene therapy (driving expression of
Nmnat1
, a key NAD
+
producing enzyme), was protective both prophylactically and as an intervention. On our highest dose, 93% of eyes did not develop glaucoma. This supports therapeutic use of vitamin B
3
in glaucoma and potentially other age-related neurodegenerations.
