NAD+ Precursors Improve Corneal Wound Healing and Nerve Regeneration in Diabetes: Preclinical Findings

Synopsis

Nicotinamide adenine dinucleotide (NAD+) is a vital molecule that supports energy metabolism, cell repair, and tissue regeneration. In diabetes, chronically high blood sugar disrupts these processes, leading to delayed corneal wound healing and nerve damage in the eye. Researchers found that in both type 1 diabetic mice and type 2 diabetic patients, hyperglycemia lowered NAD+ levels and suppressed nicotinamide phosphoribosyltransferase (NAMPT)—a key enzyme in NAD+ biosynthesis. When NAMPT was blocked in healthy mice, either through gene silencing or chemical inhibition, their corneal healing slowed dramatically, mirroring the diabetic condition. However, replenishing NAD+ or its natural precursors, such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), restored normal healing by improving cell proliferation and migration in the corneal epithelium. In diabetic mice, topical or systemic treatment with NAD+, NMN, or NR not only accelerated corneal and nerve regeneration but also reactivated SIRT1, an NAD+-dependent enzyme that promotes tissue repair. This was accompanied by renewed activation of signaling pathways involving EGFR, AKT, and ERK1/2, all essential for epithelial recovery and corneal sensitivity. Overall, the study shows that hyperglycemia reduces NAD+ production, impairing corneal healing, while NAD+ precursor supplementation—especially nicotinamide riboside—can restore repair mechanisms. These findings suggest a promising therapeutic approach for diabetic eye complications using safe, vitamin B3-based molecules.

Journal

Metabolism