A team of researchers led by Mount Sinai has made significant strides in understanding stem cell populations and mechanisms linked to age-related degradation in glands crucial for eye health. Their findings, published in Nature Communications on February 15, could pave the way for novel therapeutic strategies to combat evaporative dry eye disease, a prevalent condition among older individuals.
Meibomian glands, tiny oil-secreting glands located along the eyelid edges, produce meibum—a lipid-rich substance that prevents tear evaporation and safeguards the eye surface. Age-related shrinkage of these glands may occur due to stem cell exhaustion and is often associated with evaporative dry eye disease, characterized by swollen eyelids, itchy eyes, or blurred vision. While treatments like warm compressions, artificial tears, and thermal pulsation can alleviate symptoms somewhat, they are far from fully effective.
In their study, the researchers identified specific markers for stem cell populations that sustain distinct regions of meibomian glands. They also uncovered a crucial role played by the hedgehog (Hh) cell-cell signaling pathway in regulating meibomian gland stem cell proliferation and tissue regeneration. Their research further revealed that heightened Hh signaling is a hallmark of human meibomian gland carcinoma, an aggressive eyelid cancer.
Interestingly, aged glands exhibit decreased Hh and epidermal growth factor receptor (EGFR) signaling, alongside impaired innervation and diminished collagen production in niche fibroblasts. This suggests that both the glandular epithelial cells and their surrounding microenvironment contribute to age-related degeneration.
The team’s discoveries imply that targeting Hh and EGFR signaling could stimulate stem cell activity within meibomian glands, potentially offering a promising therapeutic approach for treating evaporative dry eye disease. Currently, despite the high prevalence of this condition, the mechanisms controlling homeostasis in meibomian glands are not well understood.
“We hope that our work will eventually lead to new and more effective therapies for this very common issue,” said Sarah E. Millar, PhD, senior author and Dean for Basic Science at the Icahn School of Medicine at Mount Sinai, as well as a professor specializing in gene and cell medicine, director of the Institute for Regenerative Medicine, and head of the Black Family Stem Cell Institute.
To conduct their research, the team utilized a mouse model system due to its similarity to human meibomian glands. They employed various analytical methods including single nuclear RNA sequencing, in vivo lineage tracing, ex vivo live imaging, and genetic gain- or loss-of-function studies. Additionally, they examined gene expression patterns in normal human eyelid samples as well as those affected by human meibomian gland carcinoma.
Dr. Millar emphasized future research will focus on preclinical studies to assess whether small molecules capable of activating Hh and EGFR signaling can reverse age-related degeneration in meibomian glands. The study also benefited from the contributions of researchers from Johns Hopkins University, the University of Michigan, and the University of Pennsylvania.
