Intracrine Activity in Meibomian Gland Dysfunction and Treatment with NAD Precursor, in Mice

Article: Mutant mice shed no tears
Source: Kyoto University (Japan)
Published: March 10, 2022

The most common cause of dry eyes is age-associated dysfunction of the meibomian glands, which are glands in the eyelids and produce the lipid layer of the tear film that prevents tear evaporation. This age-related dysfunction is thought to be due to a decline of the sex steroid hormones testosterone and estrogen, produced by the enzyme 3-hydroxyl-steroid dehydrogenase (3-HSD). Though the sex steroid hormones are classically associated with the endocrine organs, and travel throughout the body through the bloodstream, a new study by researchers in Japan using a genetically modified mouse model indicate that the meibomian glands depend on a more recently discovered intracrine system in which the hormone acts in the tissue where it is synthesized. Lead author of the study states, "Indeed, disturbed intracrine 3-HSD enzyme activity in mutant mice was found to result in atrophy of the gland, which further led to the disorder." The enzyme 3-HSD is of particular interest for its circadian activity, which regulates behaviors such as sleep, menstrual cycles, and hormone secretion. In the meibomian glands, 3-HSD is regulated by cofactor nicotinamide adenine dinucleotide (NAD), a coenzyme found in every cell and also sold as an over-the-counter supplement. When nicotinamide mononucleotide (NMN), a NAD precursor, is administered topically to mice before sleep, when 3-HSD activity peaks, it elevated the amount of NAD needed to reboot 3-HSD activity. Periodic administration of NMN in mice 4 times nightly over 90 days reduced atrophy of the meibomian glands, thereby alleviating dryness of the eyes. The researchers emphasize NMN's benefits in not only being a local therapy, but also a non-steroidal agent, which avoids the adverse or unanticipated effects of hormones.

Mouse eyes treated with vehicle (left eye) and NAD precursor nicotinamide riboside or nicotinamide mononucleotide (right eye); arrows indicate areas of epithelial defect in eyes not treated with active agent 

My rating of this study: ⭐⭐

Sasaki L, Hamada Y, Yarimizu D, et al. "Intracrine activity involving NAD-dependent circadian steroidogenic activity governs age-associated meibomian gland dysfunction." Nature Aging.  2:105-114. 10 February 2022. https://doi.org/10.1038/s43587-021-00167-8