Neuroprotective effects and mechanisms of action of nicotinamide mononucleotide (NMN) in a photoreceptor degenerative model of retinal detachment.
Aging (Albany NY)
; 12(24): 24504-24521, 2020 12 29.
Article
em En
| MEDLINE
| ID: mdl-33373320
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Degeneração Retiniana
/
Estresse Oxidativo
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Fármacos Neuroprotetores
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Células Fotorreceptoras de Vertebrados
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Mononucleotídeo de Nicotinamida
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article