The age-related failure of the glands around the eye to generate the right mix of compounds to form tears is not given a great deal of thought by most people, at least until it happens to them. Dry eye syndrome is unpleasant to experience, but in world in which cardiovascular disease and cancer exist, the causes of the age-related onset of dry eye syndrome are perhaps not as well studied as they might be. Resources are directed to more severe issues.
Researchers here note age-related changes in a stem cell population that supports one of the glands around the eye. Stem cell populations in general decline in function with age, and much of this appears to be an inappropriate reaction to the aged environment. Evidence accumulated in the study of muscle stem cells and hematopoietic stem cells suggests that aged tissue maintenance could be improved by forcing stem cells back to work, but the specific approaches needed are likely to vary widely from tissue to tissue.
Meibomian glands secrete lipid-rich meibum, which prevents tear evaporation. Aging-related Meibomian gland shrinkage may result in part from stem cell exhaustion and is associated with evaporative dry eye disease, a common condition lacking effective treatment. The identities and niche of Meibomian gland stem cells and the signals controlling their activity are poorly defined.
Using single cell RNA sequencing, in vivo lineage tracing, ex vivo live imaging, and genetic studies in mice, we identify markers for stem cell populations that maintain distinct regions of the gland and uncover Hedgehog (Hh) signaling as a key regulator of stem cell proliferation. Consistent with this, we show that human Meibomian gland carcinoma exhibits increased Hh signaling. Aged glands display decreased Hh and EGF signaling, deficient innervation, and loss of collagen I in niche fibroblasts, indicating that alterations in both glandular epithelial cells and their surrounding microenvironment contribute to age-related degeneration. These findings suggest new approaches to treat aging-associated Meibomian gland loss.
Link: https://doi.org/10.1038/s41467-025-56907-6
View the full article at FightAging
