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Aging-US: Nicotinamide mononucleotide in degenerative model of retinal detachment

01-19-2021

Aging-US published "Neuroprotective effects and mechanisms of action of nicotinamide mononucleotide (NMN) in a photoreceptor degenerative model of retinal detachment" which reported that here, the authors investigated nicotinamide mononucleotide, a precursor of nicotinamide adenine dinucleotide, in a retinal detachment 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, and a preservation of the outer nuclear layer thickness.

NMN administration significantly increased NAD levels, SIRT1 protein expression, and heme oxygenase-1 expression.

Delayed NMN administration still exerted protective effects after RD.

This Aging-US article concludes that NMN administration exerts neuroprotective effects on photoreceptors after RD and oxidative injury, suggesting a therapeutic avenue to treating photoreceptor degeneration.

"This Aging-US article concludes that NMN administration exerts neuroprotective effects on photoreceptors"

Dr. Demetrios G. Vavvas from Harvard Medical School said, "Major photoreceptor degenerative diseases are primarily age-related eye disorders, leading to severe vision impairment or irreversible vision loss."

Despite distinct differences between these diseases, the separation of photoreceptors from the underlying retinal pigment epithelium or a loss of functional RPE, and eventual photoreceptor death is common to all of them.

Since photoreceptors are highly metabolic, nutrient deprivation from the separated RPE induces the pathological responses that result in permanent neuronal loss.

Fortunately, the separation of photoreceptors from the RPE can be well-modeled in animals.

Figure 7. Protective effects of delayed NMN administration to retinal detachment (RD). (A) A flow chart for the in vivo experiments. (B–E) Delayed NMN administration still have protective effect to outer nuclear layer (ONL) thickness 7 days post RD. N = 3 to 4 eyes per group. Scale bar=50 μm. (C–F) Reduced number of CD11b+ infiltrating macrophages (red) in delayed NMN-treated groups compared to vehicle. N = 3 eyes per group. Scale bar: 100 μm. (D–G) No significance was found between NMN and vehicle treated retinas of the GFAP (green). N = 3 eyes per group. Scale bar: 50 μm. Statistical significance was analyzed with the unpaired Student's t-test. *p<0.05. **p<0.01. ***p<0.001. Data are mean ± SEM.

To date, however, little is known about the role of NAD when photoreceptors are separated from the RPE and whether the NAD and SIRT1 may play a role in protecting photoreceptors during their separation from the underlying RPE.

The Vavvas Research Team concluded in their Aging-US Priority Research Paper, "our study demonstrates the neuroprotective effects of NMN supplementation in rescuing photoreceptor degeneration after RD. NMN treatment was associated with an increase in NAD+ and SIRT1 levels in the injured retina, leading to anti- apoptotic, anti-inflammatory, and antioxidant effects. The therapeutic effect of NMN may occur at least partially through the activation of SIRT1/HO-1 signaling. These results provide an impetus for studies in larger animals and humans with photoreceptor degeneration in a clinical setting"

Full Text - https://www.aging-us.com/article/202453/text

Correspondence to: Demetrios G. Vavvas email: demetrios_vavvas@meei.harvard.edu

Keywords: nicotinamide mononucleotide, photoreceptor degeneration, NAD+, SIRT1, neuroprotection

About Aging-US:

Cancer and aging are two sides of age-related tumorigenesis.

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)

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