Systemic Treatment with Nicotinamide Riboside Is Protective in Two Mouse Models of Retinal Ganglion Cell Damage

• Type of Material: Article
• Authors: Xian Zhang, Atlanta VA Center for Visual and Neurocognitive Rehabilitation; Nan Zhang, Atlanta VA Center for Visual and Neurocognitive Rehabilitation; Micah A. Chrenek, Emory University; Preston E. Girardot, Atlanta VA Center for Visual and Neurocognitive Rehabilitation; Jiaxing Wang, Emory University; Jana T. Sellers, Atlanta VA Center for Visual and Neurocognitive Rehabilitation; Eldon Geisert Jr, Emory University; Charles Brenner, City Hope National Medical Center; John Nickerson, Emory University; Jeffrey Boatright, Emory University; Ying Li, Atlanta VA Center for Visual and Neurocognitive Rehabilitation
• Language: English
• Date: 2021-06-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/pharmaceutics13060893
• Title of Journal or Parent Work: PHARMACEUTICS
• Volume: 13
• Issue: 6
• Grant/Funding Information: This research was funded by the BrightFocus Founation (JHB and YL), VA I21RX001924 (JHB and EEG); the Abraham J. and Phyllis Katz Foundation (JHB); the joint training program between Emory University School of Medicine and Xiangya School of Medicine, Central South University. China Scholarship Council (201806370277 XZ and NZ); NIH R01EY028859 (JHB); NIH R01EY021592 (JMN); NIH R01EY028450 (JMN); NIH R01EY031042 (EEG and JHB); VA I01RX002806 (JHB); VARR&D C9246C (Atlanta VAHCS); NIH P30EY06360 (Emory University); an unrestricted departmental award from Research to Prevent Blindness. Inc. to the Ophthalmology Department at Emory University, and the Roy J. Carver Trust (CB).
• Keywords: neuroprotection; DEGENERATION; optic nerve crush; Science & Technology; Life Sciences & Biomedicine; MOLECULAR-BIOLOGY; Pharmacology & Pharmacy; SAFETY; OPTIC-NERVE; OCULAR HYPERTENSION; MITOCHONDRIAL; NEURODEGENERATION; microbead; ERG; retinal ganglion cell; NAD(+); GLAUCOMA; GENE; nicotinamide riboside
• Research Categories: Biology, Neuroscience; Gerontology; Biology, Molecular; Health Sciences, Opthamology

Abstract

Glaucoma etiology often includes retinal ganglion cell (RGC) death associated with elevated intraocular pressure (IOP). However, even when IOP is managed well, disease can progress. It is thus important to develop therapeutic approaches that directly protect RGCs in an IOP-independent manner. Compromised nicotinamide adenine dinucleotide (NAD+) metabolism occurs in neurode-generative diseases, including models of glaucoma. Here we report testing the protective effects of prophylactically systemically administered nicotinamide riboside (NR), a NAD+ precursor, in a mouse model of acute RGC damage (optic nerve crush (ONC)), and in a chronic model of RGC degeneration (ocular hypertension induced by intracameral injection of microbeads). For both models, treatment enhanced RGC survival, assessed by counting cells in retinal flatmounts immunostained for Brn3a+. In the ONC model, treatment preserved RGC function, as assessed by pattern elec-troretinogram, and suppressed retinal inflammation, as assessed by immunofluorescence staining of retinal fixed sections for glial fibrillary acidic protein (GFAP). This is the first study to demonstrate that systemic treatment with NR is protective in acute and chronic models of RGC damage. The protection is significant and, considering that NR is highly bioavailable in and well-tolerated by humans, may support the proposition of prospective human subject studies.