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New Research Sheds Light on Potential Therapeutic Approaches for Dry Eye Disease
A research team led by Mount Sinai scientists has uncovered crucial stem cell populations and mechanisms involved in age-related degeneration of glands essential for eye function. Published in Nature Communications on February 15, the study could pave the way for innovative treatments for evaporative dry eye disease, a common condition among the elderly.
The meibomian glands, tiny oil-producing glands located along the eyelid margins, play a vital role in preventing tear evaporation and maintaining eye surface health. However, as people age, these glands may shrink due to stem cell exhaustion, contributing to evaporative dry eye disease. This condition often leads to symptoms such as swollen eyelids, itchy eyes, and blurred vision. Existing treatments, including warm compresses, artificial tears, and thermal pulsation, offer only partial relief.
The Mount Sinai researchers identified specific markers for stem cell populations responsible for maintaining different areas of the meibomian glands. Their study also highlighted the hedgehog (Hh) cell-cell signaling pathway as a crucial regulator of meibomian gland stem cell proliferation and tissue regeneration. Notably, excessive Hh signaling was found to be a hallmark of meibomian gland carcinoma, a rare but aggressive eyelid cancer.
Further investigations revealed that aged meibomian glands exhibit decreased Hh and epidermal growth factor receptor (EGFR) signaling, along with impaired nerve connections and a loss of collagen in surrounding fibroblasts. These findings suggest that both glandular epithelial cells and their surrounding microenvironment contribute to age-related degeneration. As a result, targeting Hh and EGFR signaling pathways to stimulate stem cell activity could serve as a potential therapeutic approach for treating evaporative dry eye disease.
“Despite the high prevalence of dry eye disease, the stem cells and molecular mechanisms regulating meibomian gland homeostasis and their deterioration with aging remain poorly understood,” said senior author Dr. Sarah E. Millar, Dean for Basic Science at the Icahn School of Medicine at Mount Sinai. “We hope that our research will lead to more effective treatments for this widespread condition.”
The study primarily used a mouse model system due to the structural similarities between mouse and human meibomian glands. Similar to their human counterparts, aging mouse glands exhibit reduced size and fewer secretory cells. The research team employed advanced methodologies, including single-nuclear RNA sequencing, in vivo lineage tracing, ex vivo live imaging, and genetic manipulation studies. They also analyzed gene expression in human eyelid samples and meibomian gland carcinoma cases.
Looking ahead, Dr. Millar and her team plan to conduct preclinical studies to evaluate whether small molecules that activate Hh and EGFR signaling can reverse age-related degeneration in meibomian glands. Researchers from Johns Hopkins University, the University of Michigan, and the University of Pennsylvania contributed to this groundbreaking study.
For more information, refer to the published study: 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.
Disclaimer: This article is for informational purposes only and does not constitute medical advice. Individuals experiencing eye-related issues should consult a healthcare professional for diagnosis and treatment options.
