Purpose: Diabetes mellitus has been shown to be associated with and complicated by dry eye syndrome. We sought to examine and compare the tear film proteome of type 2 diabetic patients with or without dry eye syndrome and normal subjects using two-dimensional nano-liquid chromatography coupled with tandem mass spectrometry (MS)-based proteomics.
Methods: Tears were collected from eight type 2 diabetes patients with dry eye syndrome, eight type 2 diabetes patients without dry eye syndrome, and eight normal subjects. Tear breakup time (BUT) was determined, and tear proteins were prepared and analyzed using two-dimensional strong cation-exchange/reversed-phase nano-scale liquid chromatography MS. All MS/MS spectra were identified by using SEQUEST against the human International Protein Index (IPI) database and the relative abundance of individual proteins was assessed by spectral counting.
Results: Tear BUT was significantly lower in patients with diabetes and dry eye syndrome than in patients with diabetes only and normal subjects. Analysis of spectral counts of tear proteins showed that, compared to healthy controls, patients with diabetes and dry eye syndrome had increased expression of apoptosis-related proteins, like annexin A1, and immunity- and inflammation-related proteins, including neutrophil elastase 2 and clusterin, and glycometabolism-related proteins, like apolipoprotein A-II.
Conclusions: Dry eye syndrome in diabetic patients is associated with aberrant expression of tear proteins, and the findings could lead to identification of novel pathways for therapeutic targeting and new diagnostic markers.
Keywords: diabetes mellitus; dry eye; mass spectrometry; proteomics; tear.