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Nicotinamide provides neuroprotection in glaucoma by protecting against mitochondrial and metabolic dysfunction
- Source :
- Redox Biology, Vol 43, Iss, Pp 101988-(2021), Tribble, J R, Otmani, A, Sun, S, Ellis, S A, Cimaglia, G, Vohra, R, Jöe, M, Lardner, E, Venkataraman, A P, Domínguez-Vicent, A, Kokkali, E, Rho, S, Jóhannesson, G, Burgess, R W, Fuerst, P G, Brautaset, R, Kolko, M, Morgan, J E, Crowston, J G, Votruba, M & Williams, P A 2021, ' Nicotinamide provides neuroprotection in glaucoma by protecting against mitochondrial and metabolic dysfunction ', Redox Biology, vol. 43, 101988 . https://doi.org/10.1016/j.redox.2021.101988
- Publication Year :
- 2021
- Publisher :
- Elsevier, 2021.
-
Abstract
- Nicotinamide adenine dinucleotide (NAD) is a REDOX cofactor and metabolite essential for neuronal survival. Glaucoma is a common neurodegenerative disease in which neuronal levels of NAD decline. Repleting NAD via dietary supplementation of nicotinamide (a precursor to NAD) is effective in preventing retinal ganglion cell neurodegeneration in mouse models. Supporting this, short-term oral nicotinamide treatment in human glaucoma patients provides a recovery of retinal ganglion cell function implying a protection of visual function. Despite this, the mechanism of neuroprotection and full effects of nicotinamide on retinal ganglion cells is unclear. Glaucoma is a complex neurodegenerative disease in which a mix of healthy, stressed, and degenerating retinal ganglion cells co-exist, and in which retinal ganglion cells display compartmentalized degeneration across their visual trajectory. Therefore, we assess the effects of nicotinamide on retinal ganglion cells in normal physiological conditions and across a range of glaucoma relevant insults. We confirm neuroprotection afforded by nicotinamide in rodent models which represent isolated ocular hypertensive, axon degenerative, and mitochondrial degenerative insults. We define a small molecular weight metabolome for the retina, optic nerve, and superior colliculus which demonstrates that ocular hypertension induces widespread metabolic disruption that can be prevented by nicotinamide. Nicotinamide provides these neuroprotective effects by increasing oxidative phosphorylation, buffering and preventing metabolic stress, and increasing mitochondrial size and motility whilst simultaneously dampening action potential firing frequency. These data support continued determination of the utility of long-term NAM treatment as a neuroprotective therapy for human glaucoma.One Sentence SummaryThe NAD precursor nicotinamide has a potent neuroprotective effect in the retina and optic nerve, targeting neuronal function, metabolism, and mitochondrial function.
- Subjects :
- Niacinamide
Retinal Ganglion Cells
0301 basic medicine
Medicine (General)
genetic structures
QH301-705.5
Clinical Biochemistry
Nicotinamide adenine dinucleotide
Mitochondrion
Pharmacology
Biochemistry
Neuroprotection
Retinal ganglion
Retina
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
R5-920
medicine
Animals
Humans
Metabolomics
Retinal ganglion cell
Axon
Biology (General)
Nicotinamide
business.industry
Chemistry
Organic Chemistry
Neurodegenerative Diseases
Glaucoma
eye diseases
Mitochondria
Disease Models, Animal
Ophthalmology
030104 developmental biology
medicine.anatomical_structure
Metabolism
Oftalmologi
Optic nerve
NAD+ kinase
sense organs
business
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 22132317
- Volume :
- 43
- Database :
- OpenAIRE
- Journal :
- Redox Biology
- Accession number :
- edsair.doi.dedup.....f2b7262f22fb5249dc95c75d737e8e19