Mount Sinai Researchers Identify Key Mechanisms Behind Age-Related Meibomian Gland Dysfunction

A research team led by Mount Sinai has identified stem cell populations and molecular mechanisms that contribute to age-related degeneration of the meibomian glands, which play a crucial role in maintaining eye health. Published in Nature Communications, these findings may pave the way for new therapeutic approaches to treat evaporative dry eye disease (EDED), a common condition in older adults.

Understanding the Role of Meibomian Glands in Eye Function

The meibomian glands, located along the eyelid margins, secrete lipid-rich meibum that prevents tear evaporation and protects the eye surface. Aging-related shrinkage of these glands, partially due to stem cell exhaustion, is closely linked to evaporative dry eye disease, leading to symptoms such as:

       • Swollen eyelids

       • Itchy, irritated eyes

       • Blurred vision

While current treatments like warm compresses, artificial tears, and thermal pulsation therapy offer symptom relief, they remain only partially effective.

Key Findings: The Role of Stem Cells and Signaling Pathways

The research team identified specific stem cell markers that maintain distinct regions of the meibomian glands and uncovered the hedgehog (Hh) signaling pathway as a critical regulator of stem cell proliferation and tissue regeneration.

Notable Discoveries

       • Hh signaling is essential for meibomian gland function but declines with age.

       • Reduced epidermal growth factor receptor (EGFR) signaling contributes to gland degeneration.

       • Aging glands show impaired innervation and a loss of collagen in fibroblast niches, further accelerating dysfunction.

       • Increased Hh signaling is a hallmark of human meibomian gland carcinoma, a rare and aggressive eyelid cancer.

These findings suggest that targeting Hh and EGFR signaling to stimulate stem cell activity in the meibomian glands could be a potential therapeutic strategy for treating evaporative dry eye disease.

Expert Insights on the Study

Dr. Sarah E. Millar, Senior Author and Dean for Basic Science at the Icahn School of Medicine at Mount Sinai, emphasized the significance of these findings:

"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. We hope that our work will eventually result in new, more effective therapies for this very common condition."

Advanced Research Methods and Future Directions

To conduct this study, researchers used a mouse model system due to its structural and functional similarities to human meibomian glands. The team employed advanced techniques, including:

       • Single-nuclear RNA sequencing

       • In vivo lineage tracing

       • Ex vivo live imaging

       • Genetic gain- and loss-of-function studies

Additionally, gene expression was analyzed in normal human eyelid samples and human meibomian gland carcinoma.

Next Steps in Research

Dr. Millar and her team are now focusing on preclinical studies to evaluate whether small molecules that activate Hh and EGFR signaling can rescue age-related meibomian gland degeneration. This research involved collaborators from Johns Hopkins University, the University of Michigan, and the University of Pennsylvania.

As further studies advance, these findings could lead to innovative treatments that go beyond symptom management to address the root causes of evaporative dry eye disease.

Reference:

Xuming Zhu et al, Identification of Meibomian gland stem cell populations and mechanisms of aging, Nature Communications (2025). DOI: 10.1038/s41467-025-56907-6