Axonal protection by nicotinamide riboside with inhibition of p62 in TNF-induced optic nerve degeneration

Abstract

Purpose : To examine the effect of nicotinamide riboside (NR) on TNF-induced optic nerve degeneration and to investigate whether it alters autophagic status in optic nerve. We also examined the localization of nicotinamide riboside kinase 1 (NRK1) in retina and optic nerve.

Methods : Adult male Wistar rats were received intravitreal injection of TNF alone, concomitant injection of 2, 20, or 200 pmol NR and TNF, or NR alone. The p62 protein levels in optic nerve were examined to evaluate autophagic flux. Immunohistochemical analysis was performed to localize NRK1 expression. The effect of NR on TNF-induced axon loss was determined by morphometric analysis.

Results : Morphometric analysis showed substantial axonal protection by NR against TNF-induced axon loss. TNF-induced increment of p62 protein level was significantly inhibited by NR administration. NR administration alone significantly decreased p62 level in optic nerve compared with the basal levels. Immunohistochemical analysis showed that NRK1 exists in retinal ganglion cells (RGCs) and nerve fibers.

Conclusions : NRK1 which is a downstream enzyme for NR biosynthesis pathway, exists in RGCs. NR exerts axonal protection in TNF-induced optic nerve degeneration with possible involvement of upregulated autophagy.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.