Seminar Title: Hyaluronan (HA) prevents age-related meibomian gland dysfunction
Time: 3 p.m. via Zoom
Speaker Bio: Dr. Vivien J. Coulson- Thomas is an Associate Professor in Vision Science. Dr. Coulson- Thomas completed post-doctoral training in glycosciences and neurobiology at the University of Cambridge in the United Kingdom, and in ophthalmology at the University of Cincinnati. She earned her B.S. in Biomedicine and her MSc and PhD in molecular biology from the Federal University of Sao Paulo. Throughout her education, Dr. Coulson- Thomas earned various awards including the JBC/Herb Tabor Young Investigator Award from the Journal of Biological Chemistry in 2014, British Society of Matrix Biology Young Investigator Award in 2015, the award for excellence in Research, scholarship and creative activity from the University of Houston in 2022, and most recently the Endre Balazs & Janet Denlinger Award from the international society for hyaluronan sciences. She has over 25 years’ experience in the field of glycosciences, and over 15 years’ experience working with the Ocular Surface, with almost 50 published pier reviewed papers. Her research focuses on studying how the extracellular matrix regulates the development, homeostasis and pathology of the ocular surface for which she currently has two RO1 grants from NEI. Most recently, her lab is working on understanding how changes in the extracellular matrix with aging affect dry eye disease.
Seminar Summary: The prevalence of dry eye disease (DED) ranges from ~5 to 50%, with ~85% of all cases being caused by Meibomian gland dysfunction (MGD). As humans and mice age, their Meibomian glands (MGs) undergo age-related changes resulting MG atrophy and dropout, named age related-MGD (ARMGD). The etiology of ARMGD remains elusive, which makes developing therapies to prevent ARMGD extremely challenging. We previously demonstrated that hyaluronan (HA) regulates MG morphogenesis and homeostasis, with an increase in HA leading to an increase in both the number of meibocytes and acini, and, consequently, enlarged glands. We are currently investigating the role of HA in the aging MG, and its therapeutic potential for preventing ARMGD. For such, hyaluronan synthase (Has) knockout mice were aged and compared to age matched wt mice. Our data shows that at 1 year, Has1-/-Has3-/- mice present significantly enlarged MGs, compared to age-matched wt mice and compared to all adult mice. At 2 years, wt mice present severe MG atrophy and dropout, while aged matched Has1-/-Has3-/- mice present healthy glands. As wt mice age, they present a loss of HA surrounding the MG and changes in the composition of the HA matrix, which is correlated with MG atrophy. A loss of HA surrounding the MG in wt mice precedes MG atrophy. Whereas, in contrast, Has1-/-Has3-/- mice present a significant increase in HA deposition, and, consequently do not present MG atrophy. A decrease in HA synthesis in Has1-/-Has3-/- mice, via administration of a chemical inhibitor, is enough to cause MGD. Taken together, our data shows that increasing the HA matrix surrounding the MG can prevent ARMGD in mice.