The role of (O-acyl)-Omega-Hydroxy Fatty Acids in Human Lipid Layer Structure and Function in Health and Meibomian Gland Dysfunction (PI, Jason Nichols)

Meibomian gland dysfunction (MGD) is the most frequent ophthalmic disease impacting patients in clinical practice. Yet, there are no Food and Drug Administration approved pharmaceutical treatments for MGD and there are few, if any, such treatments on the horizon. This is due to lack of understanding of mechanisms of the disease that relate meibum and tear film composition to structure and function of the tear film.

MGD is the primary type of evaporative dry eye disease, one of the two major classifications of dry eye diseases. Although this condition is so frequent, occurring in up to 69% of the US population, little is known about the structure and function relationship between the meibum/tear film and the biochemical components in this disease. It is well established that MGD challenges ocular surface homeostasis. For instance, a uniform tear film “lipid layer” (made up primarily of meibum components secreted by the meibomian glands) normally retards aqueous evaporation on the ocular surface, maintaining a relatively consistent aqueous osmolality. With biochemical changes to the meibum and tear film, the normal structure of the tear film/lipid layer is compromised leading to tear film instability, evaporation, hyperosmolarity and desiccating stress. However, there has been little to no research that has quantitatively identified the exact biochemical changes in meibum in MGD that are associated with the structural changes to the tear film lipid layer.

The traditional methods of determining meibum and tear film biochemical composition, and tear film and lipid layer structure and function (in vivo) are sometimes qualitative, lacking precision/accuracy/sensitivity, or lacking clinically significant association with symptoms that are frequently reported in MGD. The innovative methods proposed in this research overcome most of these issues. Our newer analytical lipidomic approaches have led to greater insight into the fundamental changes that occur in the meibum in meibomian gland dysfunction, most recently concerning (O-acyl)-omega-hydroxy fatty acids (OAHFAs). Further, we have developed quantitative optical imaging methodologies that allow us to non-invasively measure the structure and function of the tear film and lipid layer in vivo in humans; we are therefore positioned to combine these approaches to achieve insights not possible before.

The goals of this research are to understand the biochemical changes in meibum associated with an alteration in the structure of the lipid layer and concurrent tear film instability and dysfunction in humans.