Tear levels and activity of matrix metalloproteinase (MMP)-1 and MMP-9 in vernal keratoconjunctivitis.
OBJECTIVE
To study levels and activity of matrix metalloproteinase (MMP)-1 and -9 and their tissue inhibitor (TIMP-1) in tears of patients with vernal keratoconjunctivitis (VKC), with and without severe corneal damage.


METHODS
Tear samples were obtained from 16 patients with active VKC and 10 normal control subjects, after clinical evaluation and tear cytology. Tear levels of pro-MMP-1, pro-MMP-9, and TIMP-1 were measured by enzyme-linked immunosorbent assay (ELISA). Collagenase and gelatinase activity were measured in tears by MMP activity assays. Immunohistochemistry was performed on a fragment of superficial keratectomy from two vernal corneal ulcers.


RESULTS
Tear levels of pro-MMP-1 and pro-MMP-9 were significantly increased in patients with VKC compared with control subjects (P < 0.001). MMP-1/TIMP-1 and MMP-9/TIMP-1 molar ratios were significantly increased (P < 0.001) in VKC. MMP-1 and MMP-9 activities were significantly increased in VKC tears compared with control samples (P < 0.005). MMP-9 activity correlated significantly with corneal involvement and giant papillae formation. Immunohistochemistry showed positive staining for MMP-9, fibronectin, and eosinophil cationic protein (ECP) on the superficial corneal stroma of the ulcer bed, but no inflammatory cells.


CONCLUSIONS
Increased levels and activity of MMP-1 and -9 and an imbalance between MMPs and TIMP may be involved in the pathogenesis of VKC.
Leonardi
Andrea
A
Department of Neuroscience, Ophthalmology and Ocular Inflammation Unit, University of Padua, Padua, Italy. andrea.leonardi@unipd.it
Brun
Paola
P
Abatangelo
Giovanni
G
Plebani
Mario
M
Secchi
Antonio G
AG
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D001798:Blood Proteins / Q000378:metabolism; D002648:Child; D003233:Conjunctivitis, Allergic / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D003315:Cornea / Q000201:enzymology; D003320:Corneal Ulcer / Q000201:enzymology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D047091:Eosinophil Granule Proteins; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D012260:Ribonucleases; D013666:Tears / Q000201:enzymology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D005353:Fibronectins; D019715:Tissue Inhibitor of Metalloproteinase-1; D007073:Immunoglobulin E; D012260:Ribonucleases; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1