The enigmatic world of tear extracellular vesicles (EVs)-exploring their role in ocular health and beyond.

Extracellular vesicles (EVs) are released by all kind of cells into the extracellular space, where they shuttle parental cell-derived molecular cargoes (DNA, RNA, proteins) to both adjacent and distant cells, influencing the physiology of target cells. Their specific cargo content and abundance in liquid biopsies make them excellent candidates for biomarker studies. Indeed, EVs isolated from various body fluids, including blood, pleural fluid, urine, cerebrospinal fluid, saliva, milk, ascites, and tears, have been recognized for their potential as biomarkers in diagnosis, monitoring treatment, and predicting outcomes for various diseases. Increasing studies suggest that tears have great promise as a noninvasive liquid biopsy source for EVs. Our aim here is to provide a comprehensive review of the exploration of tears as a noninvasive reservoir of EVs and their contents, evaluating their accessibility and potential utility as a liquid biopsy method. Additionally, the potential of tear EVs in various cancers, including ocular cancer, is discussed. Finally, the advantages and challenges of employing tear-based liquid biopsy for EVs for the disease's biomarker studies are evaluated.