Changes in Tear Matrix Metalloproteinases–9 and–2 From Patients With Climatic Droplet Keratopathy in the Argentine Patagonia

Abstract

Abstract: : Purpose: Matrix metalloproteinases (MMPs) are upregulated during degradation of epithelial and stromal tissues, and participated in remodelling of extra cellular matrix. We investigated the activity and molecular forms of MMP–9 and –2 in tear fluid of patients with climatic droplet keratopathy (CDK) in Argentine. Methods: 18 patients with CDK and 10 control subjects living in a semi deserted barren plain of Argentine Patagonia, were investigated. Complete ocular examination [slit–lamp biomicroscopy, external eye tests (total and basal Schirmer test, BUT, staining with lisamina green) and corneal aesthesiometry] was performed. Tear samples (residual + reflex) were collected with micro capillaries. MMP–9 and –2 activities were determined by gelatin zymography loading 30 ug of tear proteins into the gel and quantified by densitometry (pixels) using digital image analysis. The data were analyzed by use of the Mann–Whitney and Spearman tests being considered significant a p<0.05. Results: 17/18 patients had a bilateral disease, being asymmetric in 5 of them. There were not significant differences between patients and controls in regard to external eye evaluation tests. Corneal aesthesiometry showed that the more advanced the disease, the more profound was the corneal hypoesthesia (r=–0.53, p=0.029). In regard to corneal alterations, patients were grouped as: 1 (confluent translucent micro droplets localized in the limbic region of the horizontal meridians in 8 patients); 2 (5 patients with sub epithelial haziness in a band–shaped fashion from limbus–to–limbus through the central cornea); and 3 (5 patients with the previously described lesions and numerous evident amber–like sub epithelial droplets forming clusters). Most of the MMPs detected in patients and controls represented the latent forms. There was not significant differences in levels of pro–MMP–2 between both groups (p=0.11). Pro–MMP–9 median was found to be significantly higher in CDK patients than in controls (2891 pixels vs 1360, p=0.03). No correlations could be found between levels of pro–MMP–9 and corneal alterations. Conclusions: Both MMP–9 and –2 are present mainly in their latent forms in the tears of patients and controls. In spite of the increased levels of pro–MMP–9 in CDK patients, the lack of association with disease progression would suggest no fundamental role of this gelatinase in the evolution of CDK.

Keywords: pathology: human • degenerations/dystrophies • cornea: epithelium