NAD+ precursors protect corneal endothelial cells from UVB-induced apoptosis.

Abstract

Excessive exposure of the eye to ultraviolet B light (UVB) leads to corneal edema and opacification because of the apoptosis of the corneal endothelium. Our previous study found that nicotinamide (NIC), the precursor of nicotinamide adenine dinucleotide (NAD), could inhibit the endothelial-mesenchymal transition and accelerate healing the wound to the corneal endothelium in the rabbit. Here we hypothesize that NIC may possess the capacity to protect the cornea from UVB-induced endothelial apoptosis. Therefore, a mouse model and a cultured cell model were used to examine the effect of NAD+ precursors, including NIC, nicotinamide mononucleotide (NMN), and NAD, on the UVB-induced apoptosis of corneal endothelial cells (CECs). The results showed that UVB irradiation caused apparent corneal edema and cell apoptosis in mice, accompanied by reduced levels of NAD+ and its key biosynthesis enzyme, nicotinamide phosphoribosyltransferase (NAMPT), in the corneal endothelium. However, the subconjunctival injection of NIC, NMN, or NAD+ effectively prevented UVB-induced tissue damage and endothelial cell apoptosis in the mouse cornea. Moreover, pretreatment using NIC, NMN, and NAD+ increased the survival rate and inhibited the apoptosis of cultured human CECs irradiated by UVB. Mechanistically, pretreatment using nicotinamide (NIC) recovered the AKT activation level and decreased the BAX/BCL-2 ratio. In addition, the capacity of NIC to protect CECs was fully reversed in the presence of the AKT inhibitor LY294002. Therefore, we conclude that NAD+ precursors can effectively prevent the apoptosis of the corneal endothelium through reactivating AKT signaling; this represents a potential therapeutic approach for preventing UVB-induced corneal damage.

• Authors: Can Zhao, Wenjing Li, Haoyun Duan, Zongyi Li, Yanni Jia, Songmei Zhang, Xin Wang, Qingjun Zhou, Weiyun Shi
• Journal: American journal of physiology. Cell physiology (Am J Physiol Cell Physiol) Vol. 318 Issue 4 Pg. C796-C805 (04 01 2020) ISSN: 1522-1563 [Electronic] United States
• PMID: 32049549 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Protective Agents
• NAD
• Nicotinamide Mononucleotide

Topics

• Animals
• Apoptosis (drug effects)
• Cell Death (drug effects)
• Cells, Cultured
• Endothelial Cells (drug effects, metabolism)
• Endothelium, Corneal (drug effects, metabolism)
• Humans
• Mice
• NAD (drug effects, metabolism)
• Nicotinamide Mononucleotide (pharmacology)
• Protective Agents (pharmacology)
• Rabbits