Let There Be (Less) Light: NMN and Other NAD+ Precursors Protect the Cornea From UVB-Induced Damage

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NMN and Other NAD+ Precursors Protect the Cornea From UVB-Induced Damage

Affecting 285 million people worldwide, vision impairment and blindness cause significant reductions in independence and quality of life with substantial global economic impacts. Although vision loss can occur for hundreds of potential reasons, one such cause is excessive exposure to ultraviolet B rays (UVB). The same types of rays that cause sunburns and skin cancer, UVB exposure from sunlight, tanning beds, or other artificial lights are also highly detrimental to the eyes.

One compound that may be able to mitigate this damage is NAD+ (nicotinamide adenine dinucleotide), a vital coenzyme that every cell in our bodies requires to function properly. With age, NAD+ levels markedly decrease, leading to increased damage, disease, and dysfunction to organs and tissues — including the eyes. Previous research has found that boosting levels of NAD+ with its precursors, such as nicotinamide mononucleotide (NMN), improves outcomes of some vision-related disorders, including glaucoma and age-related macular degeneration.

In a recent study, a research team out of China looked at how using these NAD+ precursors may benefit the eyes after UVB exposure, specifically with specific cells of the cornea. In doing so, they may have found a potential therapeutic approach to this glaring issue (pun intended).

Letting in the light: The corneas are the windows to the eyes 

The cornea is a transparent protective covering of the front portion of the eye, acting as a barrier against dirt and disease-causing pathogens like bacteria and viruses that also filters and refracts the light that enters. A transparent cornea is essential for clear vision — you can imagine the cornea as the eye’s windowpane. When the window becomes thicker, damaged, or more opaque, seeing through it becomes more difficult. This increased thickness and opacity can occur from corneal damage, leading to blurred vision, sensitivity to light, and, eventually, blindness. On the outer layer covering the cornea lies the corneal epithelium, a single layer of cells that protect the cornea underneath it. Lining the cornea’s innermost layer are the corneal endothelial cells (CECs), providing barrier protection and regulating pump function — the ability to pump fluids and nutrients where they need to go in the eye.

While many factors can damage CECs, these cells are especially vulnerable to damage from UVB rays, as this part of the eye is the first point of entry for all types of light. With excessive UVB radiation, the quantity and density of functional CECs decrease, leading to impaired vision, increased opacification or cloudiness in the eyes, corneal edema or swelling, and apoptosis — also known as programmed cell death. Although apoptosis is beneficial in some organs and tissues, as it can eliminate cancerous or damaged cells, the killing off of CECs is an irreversible process. Once CECs are gone, they cannot be regenerated, in contrast to the regenerative capabilities of corneal epithelial cells in the outer layer. After reaching a certain stage of CEC loss, the only available treatment to restore lost vision is a corneal transplant. As a potential alternative to these invasive surgeries, Zhao and colleagues wondered if boosting NAD+ levels with two of its precursors, NMN and niacinamide (NIC), could prevent corneal damage and block apoptosis in both mice and cultured human CECs after UVB exposure.

On the outer layer covering the cornea lies the corneal epithelium, a single layer of cells that protect the cornea underneath it. Lining the cornea’s innermost layer are the corneal endothelial cells

The undesirable outcomes of UVB exposure

UVB rays damage the cornea by increasing oxidative stress — a buildup of inflammatory and highly reactive compounds — and causing dysfunction to our DNA and mitochondria, the cells’ energy hubs. Another pathway implicated in this corneal damage is UVB-induced inhibition of the enzyme AKT. As AKT is needed to block apoptosis, its inhibition is detrimental to CEC health and survival. In this study, the research team looked at the corneas of mice after 48 hours of UVB exposure. As expected, the mice had significantly increased opacity and thickness of the cornea, lower CEC density, and increased CEC apoptosis after UVB radiation. 

Additionally, the UVB exposure markedly reduced corneal NAD+ levels and NAMPT activity, the rate-limiting enzyme that uses another related compound called nicotinamide to generate NMN, which then converts into NAD+. This relationship was previously unknown — as the authors describe, “To the best of our knowledge, this is the first study to report that UVB irradiation impairs NAD+ biosynthesis in the corneal endothelium.” From there, Zhao and colleagues tested whether or not administering NAD+ precursors six hours before UVB radiation could mitigate corneal damage and reduce apoptosis in mice and human CEC cultures.

NAD+ precursors negate the damage 

Pretreating the mice with injections of NIC, NMN, or NAD+ itself prevented the corneal and CEC damage seen in untreated mice. Forty-eight hours after the UVB exposure, these treated mice had clearer corneas, reduced corneal thickness, and inhibition of CEC apoptosis, which was mediated through reactivation of AKT signaling. Notably, when a compound that inhibits AKT was added to the mix, NIC and NMN did not exert the same anti-apoptosis effects, indicating that maintaining the AKT pathway is essential for this process. These results appear to translate to humans, as the cultured human CEC’s rates of survival increased and apoptosis decreased with pretreatment of NAD+ precursors before the UVB radiation.

NMN may mitigate corneal damage from UVB exposure

Is NMN the sunscreen for the eyes?

Although NMN and NIC were not able to regenerate lost corneal endothelial cells — at this point in research, nothing can — pretreatment with these NAD+ precursors did prevent cell damage and death from occurring in the first place after UVB exposure. While it’s unlikely that one would be able to acutely pretreat with these compounds before a random corneal injury occurs — we’re not psychic, after all — regularly taking NMN could potentially mitigate CEC damage and vision loss that may arise in the future. These results could be especially useful for those who work outdoors or are exposed to UVB rays often, as chronic unprotected sun exposure can significantly damage the corneas.

While we don’t know for sure the effects of NAD+ precursors on actual humans’ corneas (we do know it benefits cultured human CECs), supplemental NMN may be a low-risk option for protecting your eyes from UVB damage. For now, slather up (internally) with NMN but don’t forget your sunglasses.


Show references

Ebeling MC, Polanco JR, Qu J, Tu C, Montezuma SR, Ferrington DA. Improving retinal mitochondrial function as a treatment for age-related macular degeneration. Redox Biol. 2020;34:101552. doi:10.1016/j.redox.2020.101552

Zhao C, Li W, Duan H, et al. NAD+ precursors protect corneal endothelial cells from UVB-induced apoptosis. Am J Physiol Cell Physiol. 2020;318(4): C796-C805. doi:10.1152/ajpcell.00445.2019

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