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Updated: Oct 30, 2025
An Optic Nerve Crush Injury Murine Model to Study Retinal Ganglion Cell Survival
Published on: April 25, 2011
Systemic Treatment with Nicotinamide Riboside Is Protective in Two Mouse Models of Retinal Ganglion Cell Damage
Xian Zhang1,2,3, Nan Zhang1,2,3, Micah A Chrenek3
1Atlanta VA Center for Visual and Neurocognitive Rehabilitation, Decatur, GA 30033, USA.
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 neurodegenerative 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 electroretinogram, 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.
Insights
Nicotinamide riboside (NR), a NAD+ precursor, protected retinal ganglion cells (RGCs) from damage in glaucoma models. This systemic treatment offers a potential neuroprotective strategy for glaucoma patients.
Area of Science:
- Neuroscience
- Ophthalmology
- Cell Biology
Background:
- Glaucoma involves retinal ganglion cell (RGC) death, often linked to elevated intraocular pressure (IOP).
- Disease progression can occur despite controlled IOP, necessitating IOP-independent neuroprotective strategies.
- Impaired nicotinamide adenine dinucleotide (NAD+) metabolism is implicated in neurodegenerative conditions like glaucoma.
Purpose of the Study:
- To investigate the neuroprotective effects of systemically administered nicotinamide riboside (NR), a NAD+ precursor.
- To evaluate NR's efficacy in both acute and chronic mouse models of RGC damage.
Main Methods:
- Testing NR in optic nerve crush (ONC) and microbead-induced ocular hypertension mouse models.
- Assessing RGC survival via Brn3a+ immunostaining in retinal flatmounts.
- Evaluating RGC function using pattern electroretinogram and retinal inflammation via GFAP staining.
Main Results:
- Systemic NR treatment significantly enhanced RGC survival in both acute (ONC) and chronic (ocular hypertension) models.
- NR treatment preserved RGC function and suppressed retinal inflammation in the ONC model.
- NR demonstrated significant neuroprotective effects in established models of RGC damage.
Conclusions:
- Systemic NR administration provides significant neuroprotection against RGC damage in acute and chronic glaucoma models.
- NR's high bioavailability and tolerability in humans support its potential for clinical application in glaucoma.
- NR represents a promising therapeutic avenue for protecting RGCs in an IOP-independent manner.
