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M. Markoulli, E. Papas, B. A. Holden; Diurnal Variation of MMP-9 in the Tear Film. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4187.
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Aim: Matrix Metalloproteinases (MMPs) are a family of degrading enzymes whose function is to maintain and remodel tissue architecture. Upregulation of MMP-9 has been associated with recurrent corneal erosions, ocular rosacea as well as the epithelial defect which results in corneal ulceration. As conditions such as recurrent corneal erosions are exacerbated upon waking, suggesting that degrading activity is upregulated overnight, this study set out to determine the diurnal variation of MMP-9 concentration in the tears of normal subjects as well as its association with gender and age.
Tears were collected using the flush method from a group of 37 healthy, non-contact lens wearers (22 female, 15 male) aged between 18 and 46 years of age (mean 27.0 ± 6.5 years). Samples were obtained from both eyes at midday, before sleep and immediately upon waking. Total protein content (TPC) and total MMP-9 concentration was measured using the bicinchoninic acid method and sandwich enzyme-linked immunoassay respectively. Statistical analysis was performed using Repeated Measures Analysis of Variance with Bonferroni correction.
TPC was 3.4 ± 0.3mg/ml, 4.3 ± 2.3mg/ml and 16.5 ± 1.6mg/ml for midday, before sleep and upon waking respectively, the latter being significantly greater than the other two results (p<0.0005). MMP-9 concentrations at the corresponding time points were 12.3 ± 2.5ng/ml, 8.0 ± 1.9ng/ml and 2485.9 ± 297.7ng/ml. Again, the value upon waking was significantly greater than for the previous two visits (p<0.0005). For both TPC and MMP-9 concentration, no significant difference was found between gender (p=0.95 and p=0.10 respectively). A weak positive correlation was found between age and MMP-9 concentration before sleep (r2 = 0.22, p=0.02) and upon waking (r2 = 0.10, p=0.03).
During sleep, MMP-9 concentration in the tear film increases roughly 200 fold, compared with an increase in total protein of only about 4 times. These changes are only weakly correlated with age, and not different between genders.
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