Proteomic Tear Fluid Analysis in Acute Anterior Uveitis Reveals Distinct Characteristics During Active Inflammation

PURPOSE: To analyze the tear fluid proteome of non-infectious acute anterior uveitis to identify objective markers of inflammation and further dissect the underlying disease pathology. METHODS: Patients from the Uveitis arm of the German Spondyloarthritis Inception cohort with available tear fluid samples and consecutive patients attending the Ophthalmology Department were included. In total, 47 patients with unilateral, non-infectious acute anterior uveitis, including 23 with follow-up samples during non-inflamed state, and 23 healthy controls were enrolled. Tear fluid was collected using Schirmer strips from both eyes during unilateral inflammation and ≥5 months after uveitis resolution from the initially inflamed eye, and from the left eye of healthy individuals. Proteomic analysis was performed by mass spectrometry in data-independent acquisition mode. RESULTS: A total of 1,994 proteins were consistently identified in the tear fluid. Of these, 24 proteins were significantly differently expressed in the eye with active uveitis compared to the non-inflamed fellow eye: the most strongly upregulated proteins were protein S100-P, villin-like protein, and glutamine synthetase, while the most downregulated proteins were protein S100-A7, immunoglobulin kappa joining 3, and prostaglandin D2 synthase. The latter was also downregulated in active uveitis compared to follow-up and healthy controls. Compared to the post-inflammatory samples, active uveitis showed 201 differentially expressed proteins, including upregulation of proteins related to unfolded protein binding and downregulation of proteins involved in metabolic processes and energy-related pathways. CONCLUSION: Uveitis alters the tear fluid proteome, indicating the potential of identifying biomarkers useful for diagnostics and monitoring the course of inflammation.