Proteomic profiling of tear fluid in patients with atopic keratoconjunctivitis.

PURPOSE: Atopic keratoconjunctivitis (AKC) is a chronic, severe ocular surface disease associated with atopic dermatitis, which may impair vision and ultimately lead to blindness. In this study, discovery-based proteomic analysis was performed on tear samples from patients with AKC to elucidate molecular characteristics and identify proteins of interest.

METHODS

All patients underwent thorough ophthalmological examination and were divided into four subgroups: healthy controls (n = 17), atopic dermatitis without ocular surface disease (n = 11), mild (n = 65), and moderate-severe AKC (n = 32). Tear film samples collected with Schirmer's filtration paper were analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Proteins were considered significantly regulated if they demonstrated a p-value lower than 0.05, following correction for multiple hypothesis testing, and if they exhibited a fold change greater than 2.

RESULTS

A total of 2503 proteins were identified. Compared with controls, mild AKC and moderate-severe AKC showed 14 and 29 significantly regulated proteins, respectively. Mild vs moderate-severe AKC yielded 21 significantly regulated proteins. Four proteins overlapped in both mild AKC and moderate-severe AKC compared to healthy controls: Short-chain specific acyl-CoA dehydrogenase, serpin B13, non-secretory ribonuclease, and probable E3 ubiquitin-protein ligase HERC4. Regulated proteins were involved in immune-related, metabolic, and epithelial processes.

CONCLUSION

This exploratory proteomic study suggests that AKC is associated with changes in immune-related pathways, including mucosal innate immunity, eosinophil migration, and cytokine signaling, as well as metabolic processes, and epithelial differentiation and barrier function.