New research has identified an underlying molecular mechanism of age-related degeneration in the meibomian glands essential to normal eye function.

The researchers hope the discovery will lead to new therapeutic approaches for common conditions in older adults, such as evaporative dry eye disease.

“Despite the prevalence of dry eye disease, the stem cells and molecular mechanisms that control homeostasis of the meibomian gland, and are impaired in ageing, are poorly understood,” said senior author Dr Sarah E. Millar, from Mount Sinai in the United States.

The Mount Sinai research team, which included collaborators from the Johns Hopkins University, University of Michigan, and University of Pennsylvania, identified the hedgehog (Hh) cell-cell signalling pathway as a key regulator of meibomian gland stem cell proliferation and tissue regeneration.

They found that aged glands show decreased Hh and epidermal growth factor receptor (EGFR) signalling. These could be two potential new targets to stimulate stem cell activity and subsequently treat dry eye disease.

Additionally, impaired innervation and a loss of collagen in niche fibroblasts were seen in aged glands, suggesting the microenvironment may also contribute to eye disease. The full study was published in Nature Communications.1

“We hope that our work will eventually result in new, more effective therapies for this very common condition,” Dr Millar said.

Reference

1. Zhu X, Xu M, Millar SE, et al. Identification of meibomian gland stem cell populations and mechanisms of aging. Nat Commun 2025;16;1663. doi: 10.1038/s41467-02556907-6.