Tear fluid levels of MMP-8 are elevated in ocular rosacea-treatment effect of oral doxycycline

Marko Määttä, Osmo Kari, Taina Tervahartiala, Sirje Peltonen, Marjatta Kari, Matti Saari, Timo Sorsa

Research output: Contribution to journalArticleScientificpeer-review

Abstract

"Background: Ocular rosacea (OcR) is a chronic inflammatory disease especially affecting lid margins. Previous studies have shown that it is accompanied by increased levels and activation of tear fluid gelatinases. Matrix metalloproteinase 8 (MMP-8; collagenase 2) levels and activation are commonly elevated in many inflammatory conditions. Therefore we studied here whether MMP-8 concentration and activation in tear fluid are increased also in OcR, and if an oral doxycycline regimen could rectify the situation. Methods: Tear fluid samples were collected from 22 OcR patients and 22 healthy controls. The OcR patients were then treated with an oral doxycycline regimen for 8 weeks and tear fluid samples collected again after 4 and 8 weeks. Conjunctival brush cytology and patients' subjective symptoms were scored. MMP-8 concentrations in the tear fluid were assessed by immunofluorometric assay and the molecular forms and isoenzyme expression of MMP-8 were studied by Western immunoblotting. Results: The mean MMP-8 concentration was statistically significantly higher in OcR (156.8 +/- 207.4 mu g/ml) than in the normal subjects (53.5 +/- 66.7 mu g/ml) (P=0.036), but decreased to 79.2 +/- 141.6 mu g/l and 53.6 +/- 75.2 mu g/l after 4 and 8 weeks doxycycline treatment, respectively. There was a statistically significant difference between the untreated OcR and the MMP-8 results after 4 or 8 weeks of oral doxycycline (P=0.041 and 0.069, respectively) and the OcR patients experienced statistically significant relief of their subjective symptoms (P=0.0001) after the doxycycline regimen. Both the normal and OcR tear fluid contained the larger, 60-80 kDa highly- glycosylated polymorphonuclear leukocyte-type MMP-8 isoform in Western immunoblotting, but not the 45-55 kDa less glycosylated mesenchymal-type isoform. MMP-8 activation was in practice present only in the OcR samples, and was inhibited by oral doxycycline. Conclusion: MMP-8 concentration and activation degree in tear fluid are increased in OcR, probably reflecting increased inflammatory activity. Doxycycline effectively reduces these pathologically excessive levels and activation of MMP-8, and relieves patients' subjective symptoms."
Original languageEnglish
JournalGraefe's Archive for Clinical and Experimental Ophthalmology
Volume244
Pages (from-to)957-962
Number of pages6
ISSN0721-832X
DOIs
Publication statusPublished - 2006
MoE publication typeA1 Journal article-refereed

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