Introducing the blood-tear barrier: Structure, function, and disruption in ocular surface homeostasis

Tear fluid exhibits a unique molecular composition distinct from blood, suggesting the presence of a selective blood-tear barrier (BTB) that regulates molecular exchange between ocular vasculature and the tear film. Although sporadically mentioned in the literature, the structure, functional roles, and mechanisms of disruption of this barrier have not yet been characterized. Based on current evidence, this review proposes a conceptual model in which the BTB comprises three successive compartments: the tear film, the epithelial layer, and the vascular endothelium, with tight junctions playing a central role in maintaining barrier integrity. The BTB appears to play a bidirectional protective role at the ocular surface, shielding the eye from external exposure while preventing the entry of blood-derived factors. This protective function is supported by literature describing interactions with microorganisms, blood-derived factors, drugs, and environmental factors. Similar to other physiological barriers in the body, the BTB is likely susceptible to disruption or breakdown. Potential disruptors include ocular surgery, topical or systemic drugs, contact lens wear, ocular surface diseases, and systemic conditions. Understanding the structure, functional roles, and mechanisms of disruption of the BTB is essential for maintaining ocular surface health and advancing the understanding of ocular surface disease.