Single-tear proteomics for noninvasive biomarker discovery and precision medicine

In the last decades, the lacrimal fluid has gained increasing interest as a potential source of biomarkers, thanks to its accessibility, moderate complexity, and responsiveness to physiopathological conditions. Despite the still limited number of studies, tear investigation, in particular single-tear analysis, could offer unique contributions to the identification of noninvasive and easily accessible biomarkers, and to the development of a feasible approach to precision medicine. High-performance liquid chromatography-mass spectrometry (LC-MS) has led to promising approaches to tear proteomics, despite the intrinsic limitations in the sample amounts that can be collected. By ultrahigh-resolution, shotgun proteomics, we developed an effective analytical pipeline for single-tear analysis and we analyzed the tear fluid of 23 healthy volunteers, achieving high-confidence identification of 890 proteins. This study demonstrates the feasibility of single-tear quantitative proteomics, highlighting the unique contributions that this unconventional body fluid can offer to personalized approaches in biomedicine.