All Eyes on NAD+ as Preclinical Study Demonstrates Protection Against Light-Induced Retinal Degeneration
A recent study found that raising NAD+ levels in a mouse model could protect the survival and function of retinal cells, the cells responsible for sight, against damaging UV light [1].
All Eyes on NAD+
NAD+ is known to play a critical role supporting metabolically active tissues, i.e. tissues that require a lot of energy for optimal function. The human retina, the layer at the back of the eye that converts light passing through our pupils into an electric signal sent to the brain, is one such energy-expensive tissue. A review article published this year highlighted Declining levels of retinal NAD+ have been linked to diseases of the retina, including age-related macular degeneration, the leading cause of blindness in the Western world [2].
NAD+ levels throughout the body are known to decline with age. Physiological stressors, such as oxidative damage from smoking and cell-damaging UV light, can also deplete NAD+.
UV light is known to cause mutations in our DNA that disrupts cells, triggering the immune system and setting off an inflammatory cascade. These mutations can accumulate and set cells on the path towards cancer development. While excess UV light (from sun exposure) is known to cause skin cancer, UV light exposure can also damage ocular tissues, including the lens and retina. NAD+ may be important in repairing the DNA damage caused by UV light, as well as regulating the inflammation that ensues.
This latest study set out to test the hypothesis that if NAD+ depletion from aging or UV light is associated with common forms of retinal disease, could raising NAD+ prevent this damage?
Nicotinamide Riboside Prevents Retinal Damage in Mice
In this recent study published in Investigative Ophthalmology & Visual Science, investigators gave mice an NAD+ boosting compound called nicotinamide riboside (NR) the day before and morning before exposure to retinal damaging light [1].
They found that while the damaging light significantly decreased NAD+ levels in the control mice, NR administration prevented this reduction.
Preserving NAD+ also prevented the light-induced thinning of the retinal cell layer seen in the control mice. The placebo mice saw many of their retinal cells undergo apoptosis, or cellular “suicide,” following the damage, while the mice given NR did not. The control mice also had increased markers of ocular inflammation, which the NR mice did not.
Ultimately, NR administration helped to preserve retinal cell survival and function in the mice following exposure to intense light damage, which was meant to simulate the decades of exposure to UV light we experience over our lifetimes.
These findings build on earlier preclinical work studying other NAD+ precursors which identified retinal NAD+ depletion as an early feature of retinal dysfunction, including light-induced degeneration, streptozotocin-induced diabetic retinopathy, and age-associated dysfunction [3]. It was shown that mechanistically, NAD+ depletion caused metabolic dysfunction and consequent photoreceptor death. Earlier work also demonstrated that the NAD-dependent mitochondrial deacylases SIRT3 and SIRT5 play important roles in retinal homeostasis and that NAD+ depletion causes SIRT3 dysfunction [3].
Keep an Eye Out for Future Human Research
This study contributes to the growing body of preclinical evidence suggesting that raising NAD+ may help prevent damage to the retina.
Other preclinical experiments have shown that NAD+ may be critical for preserving the function of other metabolically active tissues in the face of environmental stressors, such as protecting the liver against alcohol-induced damage [4] or protecting neural cells from diet-induced inflammation [5].
Further experiments in humans are required to elucidate the role of NAD+ in macular degeneration, UV-light-induced damage, and other common diseases of the eye.