NAD+ biosynthesis and corneal wound healing in diabetic mice

The subject was corneal wound healing

This study examined the relationship between high glucose, NAD+ biosynthesis and corneal epithelial wound healing in diabetic mice. It did not demonstrate that NMN cured diabetes or lowered blood glucose in patients.

NAD+ is a coenzyme, and NMN is one of the precursors used to make it. The Japanese archive reversed that relationship in one sentence; the distinction is corrected here.

The experimental models

The researchers used streptozotocin-induced diabetic mice and created a corneal epithelial wound model. They measured NAD-related content and examined enzymes involved in NAD+ biosynthesis.

The investigation also considered corneal samples associated with human type 2 diabetes and laboratory epithelial-cell experiments. Observations in human samples are different from a clinical intervention showing treatment benefit.

Testing the role of NAMPT

NAMPT was manipulated using a targeted small interfering RNA and the inhibitor FK866. Reducing NAMPT activity in otherwise normal mice reproduced aspects of delayed epithelial wound healing.

In cell experiments, NAD+ supplementation restored some proliferation and migration responses impaired by FK866 or high-glucose exposure. These interventions were used to probe a mechanism.

Reported findings in diabetic mice

High glucose was associated with lower NAD+ content and reduced NAMPT expression in the corneal epithelium. In diabetic mice, administration of NAD+ or selected precursors, including NMN and NR, was associated with improved epithelial and nerve-regeneration measures.

The changes were accompanied by measurements involving SIRT1 and phosphorylated EGFR, AKT and ERK1/2, as well as corneal sensitivity. They concern the experimental tissue response, not a demonstration of whole-body diabetes treatment.

What the findings mean

The research suggests that impaired NAD+ biosynthesis may contribute to delayed corneal repair in the model studied. It provides a basis for further investigation of diabetic corneal complications.

It does not establish that an oral supplement heals a human corneal wound or replaces diabetes or eye care. A finished GAAH product was not tested.

Cited paper: Hyperglycemia-reduced NAD+ biosynthesis impairs corneal epithelial wound healing in diabetic mice.