Molecular perspectives on protein-modulated tear film lipid layer stability in dry eye disease

Abstract

Understanding the tear film lipid layer (TFLL) at the molecular and microphysiological levels is critical to addressing issues related to eye health and visual acuity. The composition of the TFLL, including a mixture of lipids such as wax esters and cholesterol esters, plays a key role in its ability to inhibit evaporation and maintain its interaction with the underlying aqueous layer. Recent advances in methods such as the Langmuir technique, X-ray diffraction, fluorescence imaging, and computational modeling have significantly deepened our understanding of TFLL dynamics. In particular, research has focused on how TFLL interacts with tear proteins such as lipocalin, lactoferrin, and lysozyme. These proteins are critical for maintaining the structure and spreading of the lipid layer, which in turn stabilizes the entire tear film. This review will also explore the implications of TFLL instability for conditions such as dry eye syndrome, use of contact lenses, and after ocular surgery. Ongoing research into dry eye syndrome is critical due to its prevalence and severity. Although progress has been made, many aspects of the complex functions of the TFLL remain unexplored. Future research could lead to breakthroughs in treatment and prevention, improving patients' quality of life and expanding therapeutic options. © 2025 Elsevier B.V.