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Srikanth Reddy Janga, Maria C Edman, Tao Ma, Mihir Shah, Aida Kouhi, Jingwen Chen, Frances Yarber, Sarah F Hamm-Alvarez; Longitudinal Characterization of Tear Fluid Cathepsin S, a Sjögren’s Syndrome Biomarker, in the male Non-Obese Diabetic mouse. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2484.
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© ARVO (1962-2015); The Authors (2016-present)
Sjögren’s Syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of lacrimal and salivary glands and causing decreased glandular function resulting in subsequent dry eye and dry mouth symptoms. We have previously shown that activity of the lysosomal protease, Cathepsin S (CTSS), is elevated in the tear fluid (TF) of male Non-Obese Diabetic (NOD) mice, a model of SS that spontaneously develops lacrimal gland exocrinopathy that resembles the human disease. Recently we confirmed that CTSS is elevated in TF of patients with SS compared to patients with other autoimmune diseases and healthy controls, emphasizing its potential as a biomarker for the disease. However, nothing is known about how CTSS levels are correlated with disease development and progression. Here, we investigate the changes in CTSS levels in TF and lacrimal gland (LG) of male NOD mice monthly starting at 1 month (mth) prior to onset of disease until 7 mths of age, when lymphocytic infiltration is extensive and disease is prolonged.
Carbachol-stimulated tear fluid was collected from male NOD mice at ages 1, 2, 3, 4, 5, 6 and 7 mths (n=4-11 per group), after which the mice were euthanized and LGs were retrieved for preparation of lysates. CTSS activity levels were measured in both tears and lysates using a commercial CTSS activity assay kit and normalized to total protein concentration. Statistical analysis was performed through one-way ANOVA with p≤0.05 considered significant. Values represent Mean±SEM.
TF CTSS activity was 5-fold elevated at 2, 6.6-fold at 3, 7.0 fold at 4, 8.6-fold at 5, 10-fold at 6 and 20-fold at 7 mths (1;56±0, 2;296±20, 3;340±18 4;400±14, 5; 489±19, 6;571±27 and 7;1166±66) when compared to 1 mth mice, while the activity levels in lysate showed a 11-fold increase at 2, 17 fold at 3 to 6, and 23.0 fold at 7 mths (1; 387±20, 2; 4468±161, 3; 6593±227, 4;6581±146, 5;6766±238, 6;6388±373, 7;8918±851) when compared to 1 mth mice. Detectable lymphocytic infiltration of the gland is initiated at 8 weeks in this disease model and ranged from none at 1 mth to 30% at 7 mth.
These results suggest that CTSS activity in LG and TF continues to increase beyond the early stages of disease. Relative TF CTSS activity may potentially be used clinically to reflect the extent of lacrimal gland inflammation and damage.
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