Document Type

Article

Publication Date

2018

Keywords

Glaucoma, NAD+, nicotinamide, axon degeneration, retinal ganglion cell, optic nerve head cupping

JAX Source

Commun Integr Biol 2018; 11(1):e1356956

DOI

10.1080/19420889.2017.1356956

Grant

EY11721, Jackson Laboratory Fellowships, Barbara and Joseph Cohen Foundation, Partridge Foundation, Lano Family Foundation

Abstract

Nicotinamide adenine dinucleotide (NAD) is a key molecule in several cellular processes and is essential for healthy mitochondrial metabolism. We recently reported that mitochondrial dysfunction is among the very first changes to occur within retinal ganglion cells during initiation of glaucoma in DBA/2J mice. Furthermore, we demonstrated that an age-dependent decline of NAD contributes to mitochondrial dysfunction and vulnerability to glaucoma. The decrease in NAD renders retinal ganglion cells vulnerable to a metabolic crisis following periods of high intraocular pressure. Treating mice with the NAD precursor nicotinamide (the amide form of vitamin B3) inhibited many age- and high intraocular pressure- dependent changes with the highest tested dose decreasing the likelihood of developing glaucoma by ∼10-fold. In this communication, we present further evidence of the neuroprotective effects of nicotinamide against glaucoma in mice, including its prevention of optic nerve excavation and axon loss as assessed by histologic analysis and axon counting. We also show analyses of age- and intraocular pressure- dependent changes in transcripts of NAD producing enzymes within retinal ganglion cells and that nicotinamide treatment prevents these transcriptomic changes.

Commun Integr Biol 2018; 11(1):e1356956.

Comments

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/).

Download

Share

COinS