Harnessing exosomes in dry eye disease: a triple threat approach

Dry eye disease is a chronic ocular surface disorder primarily driven by tear film instability and hyperosmolarity, which propagates inflammatory cascades leading to ocular tissue damage. Exosomes facilitate the transfer of proteins, nucleic acids, and lipids between donor and recipient cells, mediating the exchange of bioactive molecules. These vesicles demonstrate transformative potential as carriers of bioactive molecules, drug delivery vehicles, and disease biomarkers. Although exosome research in posterior segment eye diseases is extensive, studies investigating their triple functionality—therapeutic agent, drug delivery vehicle, and biomarker—in the context of dry eye remain limited and fragmented. The literature search of the PubMed database (2015–2025) was conducted using keywords related to “exosomes,” “extracellular vesicles,” “dry eye,” and their therapeutic, drug delivery, and biomarker applications, with eligible studies screened and selected according to predefined criteria. We found the multifaceted roles of exosomes in dry eye as integrated therapeutic, delivery, and diagnostic agents. We emphasize: (1) their multimodal efficacy through mechanisms such as immunomodulation, corneal repair, and neuroinflammation suppression; (2) superior drug delivery capabilities, including enhanced stability and miRNA-mediated anti-inflammatory targeting; and (3) diagnostic utility via tear- or saliva-based biomarkers for quantifying dry eye progression. Finally, we discuss current challenges in translating exosome-based strategies into clinical practice and explore future directions for advancing cell-free therapies in ophthalmology. Exosomes have emerged as transformative agents in dry eye disease management by functioning as innate immunomodulators and mediators of adaptive immune responses, while simultaneously serving as versatile therapeutic vectors, drug delivery vehicles, and precision biomarkers. While challenges such as manufacturing scalability and regulatory standardization remain to be fully addressed, exosomes unequivocally represent a paradigm shift toward precision medicine for dry eye disease.