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.