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Priority Research Paper|Volume 12, Issue 24|pp 24504—24521

Neuroprotective effects and mechanisms of action of nicotinamide mononucleotide (NMN) in a photoreceptor degenerative model of retinal detachment

Xiaohong Chen1,2, João A. Amorim4, Giannis A. Moustafa1, Jong-Jer Lee1, Zhen Yu1, Kenji Ishihara1, Yasuhiro Iesato1, Paulo Barbisan1, Takashi Ueta1, Konstantina A. Togka1, Lin Lu2, David A. Sinclair4, Demetrios G. Vavvas1,3
  • 1Angiogenesis Laboratory, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA
  • 2State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China
  • 3Department of Ophthalmology, Retina Service, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA
  • 4Department of Genetics, Blavatnik Institute, Paul F. Glenn Center for Biology of Aging Research, Harvard Medical School, Boston, MA 02115, USA
Received: July 9, 2020Accepted: November 21, 2020Published: December 29, 2020
https://doi.org/10.18632/aging.202453

Copyright: © 2020 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Currently, no pharmacotherapy has been proven effective in treating photoreceptor degeneration in patients. Discovering readily available and safe neuroprotectants is therefore highly sought after. Here, we investigated nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD+), in a retinal detachment (RD) induced photoreceptor degeneration. NMN administration after RD resulted in a significant reduction of TUNEL+ photoreceptors, CD11b+ macrophages, and GFAP labeled glial activation; a normalization of protein carbonyl content (PCC), and a preservation of the outer nuclear layer (ONL) thickness. NMN administration significantly increased NAD+ levels, SIRT1 protein expression, and heme oxygenase-1 (HO-1) expression. Delayed NMN administration still exerted protective effects after RD. Mechanistic in vitro studies using 661W cells revealed a SIRT1/HO-1 signaling as a downstream effector of NMN-mediated protection under oxidative stress and LPS stimulation. In conclusion, NMN administration exerts neuroprotective effects on photoreceptors after RD and oxidative injury, suggesting a therapeutic avenue to treating photoreceptor degeneration.