Tear fluid levels of MMP-8 are elevated in ocular rosacea--treatment effect of oral doxycycline.
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 mug/ml) than in the normal subjects (53.5+/-66.7 mug/ml) (P=0.036), but decreased to 79.2+/-141.6 mug/l and 53.6+/-75.2 mug/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.


CONCLUSIONS
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.
Määttä
Marko
M
Department of Ophthalmology, Helsinki University Central Hospital, Haartmaninkatu 4, 00029, HUS, Finland. mmaatta@mailcity.com
Kari
Osmo
O
Tervahartiala
Taina
T
Peltonen
Sirje
S
Kari
Marjatta
M
Saari
Matti
M
Sorsa
Timo
T
D000284:Administration, Oral; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015153:Blotting, Western; D004318:Doxycycline / Q000627:therapeutic use*; D005141:Eyelid Diseases / Q000188:drug therapy / Q000201:enzymology*; D005260:Female; D015200:Fluoroimmunoassay; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism*; D008875:Middle Aged; D012393:Rosacea / Q000188:drug therapy / Q000201:enzymology*; D013666:Tears / Q000201:enzymology*
D000900:Anti-Bacterial Agents; D007527:Isoenzymes; D020784:Matrix Metalloproteinase 8; D004318:Doxycycline