Nicotinamide treatment robustly protects from inherited mouse glaucoma

Communicative & Integrative Biology
Pete A WilliamsSimon W M John

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 preve...Continue Reading

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Citations

Nov 6, 2018·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Anand ManoharanSimon B Duckett
Dec 6, 2018·Current Opinion in Neurology·Neringa JurkutePatrick Yu-Wai-Man
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Aug 28, 2021·Cells·Valery I ShestopalovMarkus H Kuehn
Nov 19, 2021·JAMA Ophthalmology·Carlos Gustavo De MoraesJeffrey M Liebmann

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Datasets Mentioned

BETA
GSE90654

Software Mentioned

AxonJ

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