A team led by Mount Sinai researchers has discovered stem cell populations and mechanisms involved in age-related deterioration within glands essential for eye function. Their findings, published in Nature Communications on February 15th, may pave the way for new treatments for evaporative dry eye disease, a common condition among older adults.
Meibomian glands are small oil-producing glands located along the eyelids’ edges. They secrete meibum, an oily substance that prevents tear evaporation and protects the eye’s surface. As these glands age and shrink due to stem cell exhaustion, they can lead to evaporative dry eye disease, characterized by swollen eyelids, itchy eyes, or blurred vision.
Current treatments such as warm compressions, artificial tears, and thermal pulsation provide only partial relief from symptoms of this condition. However, the researchers have identified specific markers for stem cell populations that maintain distinct regions within meibomian glands. They also uncovered the hedgehog (Hh) signaling pathway—a vital regulator in both development and disease—as a key factor controlling meibomian gland stem cell proliferation and tissue regeneration.
The study found increased Hh signaling to be associated with human meibomian gland carcinoma, an aggressive cancer of the eyelid. Additionally, they discovered that aged glands show reduced Hh and epidermal growth factor receptor (EGFR) signaling, along with impaired innervation and loss of collagen in niche fibroblasts. These findings indicate changes within both the glandular epithelial cells themselves and their surrounding microenvironment contribute to age-related degeneration.
These discoveries suggest that targeting Hh and EGFR signaling pathways could stimulate stem cell activity in meibomian glands, potentially leading to effective therapies for evaporative dry eye disease. Despite its prevalence, understanding of the stem cells and molecular mechanisms controlling homeostasis within the meibomian gland has been limited.
Dr. Sarah E. Millar, a senior author from Mount Sinai’s Icahn School of Medicine, expressed hope that their work could eventually lead to new treatments for this common condition. She is currently Dean for Basic Science at the school and holds multiple professorships including Lillian and Henry M. Stratton Professor of Gene and Cell Medicine.
For most analyses, researchers used a mouse model system because its meibomian glands have a similar structure to those in humans and exhibit similar characteristics when aging—namely decreased size and fewer secretory cells. They conducted various studies including single nuclear RNA sequencing, in vivo lineage tracing, ex vivo live imaging, and genetic gain- or loss-of-function experiments.
The researchers also examined gene expression patterns both in normal human eyelid samples and in human meibomian gland carcinoma tissue. Dr. Millar stated that future research will include preclinical studies to determine whether small molecules that activate Hh and EGFR signaling can help reverse age-related degeneration within the meibomian glands.
Collaborators from Johns Hopkins University, the University of Michigan, and the University of Pennsylvania contributed to this study. Their findings bring new insights into understanding evaporative dry eye disease at a cellular level and offer potential avenues for more effective treatment in the future.
