Mount Sinai Team Identifies Underlying Mechanisms of Age-Related Meibomian Gland Dysfunction, Possible Treatment Options for Dry Eye Disease

New research from Mount Sinai identifies an underlying molecular mechanism of age-related degeneration in the meibomian glands essential to normal eye function. Now, this may lead to new therapeutic approaches for common conditions in older adults such as evaporated 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 aging, are poorly understood,” senior author Sarah E. Millar, PhD, Dean for Basic Science of the Icahn School of Medicine at Mount Sinai, the Lillian and Henry M. Stratton Professor of Gene and Cell Medicine, Director of the Institute for Regenerative Medicine, and Director of the Black Family Stem Cell Institute, said in a recent press release. 

Meibomian glands are tiny glands on the edges of the eyelids that secrete oils to prevent tear evaporation and protect the eye surface. The glands shrink with age, in part related to stem cell exhaustion, which can lead to dry eye disease in older adults. This condition causes a range of symptoms, including eyelid swelling, itchy eyes, and blurred vision. Management includes warm compresses, artificial tears, and thermal pulsation, but these treatments are only partially effective.

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 signaling pathway as a key regulator of meibomian gland stem cell proliferation and tissue regeneration. A mouse model system was used for their data analyses because the meibomian glands of mice are structurally and physiologically like those in humans. 

They found that aged glands show decreased Hh and epidermal growth factor receptor (EGFR) signaling. 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 earlier this month. 

“We hope that our work will eventually result in new, more effective therapies for this very common condition,” Dr. Millar said. The team’s future work will include studying if small molecules that activate Hh and EGFR signaling can impair age-related meibomian gland degeneration.