Nicotinamide provides neuroprotection in glaucoma by protecting against mitochondrial and metabolic dysfunction

Research output: Contribution to journal › Journal article › Research › peer-review

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Nicotinamide provides neuroprotection in glaucoma by protecting against mitochondrial and metabolic dysfunction. / Tribble, James R.; Otmani, Amin; Sun, Shanshan; Ellis, Sevannah A.; Cimaglia, Gloria; Vohra, Rupali; Jöe, Melissa; Lardner, Emma; Venkataraman, Abinaya P.; Domínguez-Vicent, Alberto; Kokkali, Eirini; Rho, Seungsoo; Jóhannesson, Gauti; Burgess, Robert W.; Fuerst, Peter G.; Brautaset, Rune; Kolko, Miriam; Morgan, James E.; Crowston, Jonathan G.; Votruba, Marcela; Williams, Pete A.

In: Redox Biology, Vol. 43, 101988, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Tribble, JR, Otmani, A, Sun, S, Ellis, SA, Cimaglia, G, Vohra, R, Jöe, M, Lardner, E, Venkataraman, AP, Domínguez-Vicent, A, Kokkali, E, Rho, S, Jóhannesson, G, Burgess, RW, Fuerst, PG, Brautaset, R, Kolko, M, Morgan, JE, Crowston, JG, Votruba, M & Williams, PA 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

APA

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., ... Williams, P. A. (2021). Nicotinamide provides neuroprotection in glaucoma by protecting against mitochondrial and metabolic dysfunction. Redox Biology, 43, [101988]. https://doi.org/10.1016/j.redox.2021.101988

Vancouver

Tribble JR, Otmani A, Sun S, Ellis SA, Cimaglia G, Vohra R et al. Nicotinamide provides neuroprotection in glaucoma by protecting against mitochondrial and metabolic dysfunction. Redox Biology. 2021;43. 101988. https://doi.org/10.1016/j.redox.2021.101988

Author

Tribble, James R. ; Otmani, Amin ; Sun, Shanshan ; Ellis, Sevannah A. ; Cimaglia, Gloria ; Vohra, Rupali ; Jöe, Melissa ; Lardner, Emma ; Venkataraman, Abinaya P. ; Domínguez-Vicent, Alberto ; Kokkali, Eirini ; Rho, Seungsoo ; Jóhannesson, Gauti ; Burgess, Robert W. ; Fuerst, Peter G. ; Brautaset, Rune ; Kolko, Miriam ; Morgan, James E. ; Crowston, Jonathan G. ; Votruba, Marcela ; Williams, Pete A. / Nicotinamide provides neuroprotection in glaucoma by protecting against mitochondrial and metabolic dysfunction. In: Redox Biology. 2021 ; Vol. 43.

Bibtex

@article{4dcd58f00d8a4b5180c74ec5b52b63aa,
title = "Nicotinamide provides neuroprotection in glaucoma by protecting against mitochondrial and metabolic dysfunction",
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. We assess the effects of nicotinamide (a precursor to NAD) on retinal ganglion cells (the affected neuron in glaucoma) in normal physiological conditions and across a range of glaucoma relevant insults including mitochondrial stress and axon degenerative insults. We demonstrate retinal ganglion cell somal, axonal, and dendritic neuroprotection by nicotinamide in rodent models which represent isolated ocular hypertensive, axon degenerative, and mitochondrial degenerative insults. We performed metabolomics enriched for small molecular weight metabolites for the retina, optic nerve, and superior colliculus which demonstrates that ocular hypertension induces widespread metabolic disruption, including consistent changes to α-ketoglutaric acid, creatine/creatinine, homocysteine, and glycerophosphocholine. This metabolic disruption is prevented by nicotinamide. Nicotinamide provides further 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 nicotinamide treatment as a neuroprotective therapy for human glaucoma.",
keywords = "Glaucoma, Metabolism, Metabolomics, Mitochondria, Nicotinamide, Retina, Retinal ganglion cell",
author = "Tribble, {James R.} and Amin Otmani and Shanshan Sun and Ellis, {Sevannah A.} and Gloria Cimaglia and Rupali Vohra and Melissa J{\"o}e and Emma Lardner and Venkataraman, {Abinaya P.} and Alberto Dom{\'i}nguez-Vicent and Eirini Kokkali and Seungsoo Rho and Gauti J{\'o}hannesson and Burgess, {Robert W.} and Fuerst, {Peter G.} and Rune Brautaset and Miriam Kolko and Morgan, {James E.} and Crowston, {Jonathan G.} and Marcela Votruba and Williams, {Pete A.}",
note = "Publisher Copyright: Copyright {\textcopyright} 2021 The Authors. Published by Elsevier B.V. All rights reserved.",
year = "2021",
doi = "10.1016/j.redox.2021.101988",
language = "English",
volume = "43",
journal = "Redox Biology",
issn = "2213-2317",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Nicotinamide provides neuroprotection in glaucoma by protecting against mitochondrial and metabolic dysfunction

AU - Tribble, James R.

AU - Otmani, Amin

AU - Sun, Shanshan

AU - Ellis, Sevannah A.

AU - Cimaglia, Gloria

AU - Vohra, Rupali

AU - Jöe, Melissa

AU - Lardner, Emma

AU - Venkataraman, Abinaya P.

AU - Domínguez-Vicent, Alberto

AU - Kokkali, Eirini

AU - Rho, Seungsoo

AU - Jóhannesson, Gauti

AU - Burgess, Robert W.

AU - Fuerst, Peter G.

AU - Brautaset, Rune

AU - Kolko, Miriam

AU - Morgan, James E.

AU - Crowston, Jonathan G.

AU - Votruba, Marcela

AU - Williams, Pete A.

N1 - Publisher Copyright: Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

PY - 2021

Y1 - 2021

N2 - 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. We assess the effects of nicotinamide (a precursor to NAD) on retinal ganglion cells (the affected neuron in glaucoma) in normal physiological conditions and across a range of glaucoma relevant insults including mitochondrial stress and axon degenerative insults. We demonstrate retinal ganglion cell somal, axonal, and dendritic neuroprotection by nicotinamide in rodent models which represent isolated ocular hypertensive, axon degenerative, and mitochondrial degenerative insults. We performed metabolomics enriched for small molecular weight metabolites for the retina, optic nerve, and superior colliculus which demonstrates that ocular hypertension induces widespread metabolic disruption, including consistent changes to α-ketoglutaric acid, creatine/creatinine, homocysteine, and glycerophosphocholine. This metabolic disruption is prevented by nicotinamide. Nicotinamide provides further 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 nicotinamide treatment as a neuroprotective therapy for human glaucoma.

AB - 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. We assess the effects of nicotinamide (a precursor to NAD) on retinal ganglion cells (the affected neuron in glaucoma) in normal physiological conditions and across a range of glaucoma relevant insults including mitochondrial stress and axon degenerative insults. We demonstrate retinal ganglion cell somal, axonal, and dendritic neuroprotection by nicotinamide in rodent models which represent isolated ocular hypertensive, axon degenerative, and mitochondrial degenerative insults. We performed metabolomics enriched for small molecular weight metabolites for the retina, optic nerve, and superior colliculus which demonstrates that ocular hypertension induces widespread metabolic disruption, including consistent changes to α-ketoglutaric acid, creatine/creatinine, homocysteine, and glycerophosphocholine. This metabolic disruption is prevented by nicotinamide. Nicotinamide provides further 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 nicotinamide treatment as a neuroprotective therapy for human glaucoma.

KW - Glaucoma

KW - Metabolism

KW - Metabolomics

KW - Mitochondria

KW - Nicotinamide

KW - Retina

KW - Retinal ganglion cell

U2 - 10.1016/j.redox.2021.101988

DO - 10.1016/j.redox.2021.101988

M3 - Journal article

C2 - 33932867

AN - SCOPUS:85107318878

VL - 43

JO - Redox Biology

JF - Redox Biology

SN - 2213-2317

M1 - 101988

ER -

ID: 272124355