Dry Eye: A Protein Conformational Disease

PURPOSE. The purpose of this study was to determine whether aqueous-deficient dry eyes (ADDE) is a protein conformational disease. Up to now the therapeutic regimen has been based on empirical results, but these observations may unfold new theranostic approaches for ADDE management. METHODS. Fifty ADDE patients and 46 healthy volunteers were recruited. Schirmer's test, tear breakup time, tear meniscus height, and fluorescein staining tests were conducted on the subjects. Tear protein for ADDE and control patients was collected and extracted using Schirmer's strip. Protein aggregation was studied by appraisal of average protein size, using dynamic light scattering (DLS), fast performance liquid chromatography (FPLC), and synchronous fluorescence spectroscopy (SFS). RESULTS. Dynamic light scattering data showed a comparatively higher abundance of aggregated proteins in ADDE patients than that in controls. For controls, the size distribution of tear proteins was <50 nm in diameter, whereas the size distribution for ADDE individuals was up to 300 nm in diameter. Fast performance liquid chromatography experiments in native tear proteins exhibited minimal difference in the FPLC profiles for ADDE patients and controls. Denatured tear protein FPLC profiles for patients indicated the presence of protein aggregates which were absent in controls. Our hypothesis was further verified by SFS; lower tryptophan fluorescence in ADDE patients is an indication of oxidative stress, which leads to protein aggregation. CONCLUSIONS. Aqueous-deficient dry eyes is likely to be a protein conformational disease. Unlike other conformational diseases where single proteins are involved, this may be a reflection of structural loss for a significant fraction of the tear proteome.