Abstract
Presentation Description :
Glaucoma will soon affect 80 million people worldwide. Harmfully high intraocular pressure is the strongest known contributing factor, but increased age is a key independent risk factor. Despite much progress, glaucoma mechanisms are only partially understood and improved treatments are needed. Mice provide a powerful system for hypothesis testing and experimental dissection of pathogenesis. Using specifically-designed gene expression analyses and an age-dependent, inherited, mouse, model, we have defined temporally-ordered stages of glaucoma that precede RGC dysfunction/loss. Metabolite assays building on these findings, identified an age-dependent decline in nicotinamide adenine dinucleotide (NAD) that appears to render retinal ganglion cells susceptible to metabolic failure and glaucoma when IOP is elevated. Increasing NAD levels by dietary administration of nicotinamide (the amide form of vitamin B3), is profoundly protective against glaucoma. These studies uncover a key role for altered metabolism in vulnerability to this glaucoma and suggest that glaucoma is on the spectrum of metabolic optic neuropathies.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.