Abstract
Purpose: :
To compare the presence and activity of matrix metalloproteinases (MMP) 1, 2, 3, 7, 8 and 9 in human corneal grafts obtained during penetrating keratoplasty for corneal melting with normal human corneas.
Methods: :
Ten control corneal buttons and six melted corneas were used. All patients suffered from rheumatoid arthritis (RA); in three of them RA was associated with Sjögren's syndrome, in two with peripheral ulcerative keratitis, and in one with keratoconjunctivitis sicca. MMP 1, 2, 3, 7, 8 and 9 were detected using indirect enzyme immunohistochemistry. The activities of MMP 2, 9 and MMP 3, 7 were detected in 10 control and 4 melted specimens by gelatin or casein zymography, respectively. The MMP 1 activity was detected by an MMP 1 activity assay.
Results: :
Weak staining for MMP 1, 2 and 8 were detected in normal corneal epithelium. Moderate MMP 1, 2 and 9 staining and weak staining for MMP 3, 7 and 8 were observed in the corneal epithelial fragments and in the anterior stroma of all melted corneas. Weak staining for MMP 1 and 2 was detected in the posterior stroma of all four melted corneas. A moderate presence of the proenzyme and a weak presence of the active form of MMP 2 were found in all control corneas by gelatin zymography. Only a weak presence of the MMP 9 proenzyme was detected in two out of ten controls. The active form of MMP 2 was strongly present in 3 of 4 melted corneas; one of these corneas also showed the strong presence of the proenzyme. The remaining melted cornea displayed a weak presence of both the proenzyme and the active form. The presence of both forms of MMP 9 was extremely strong in three and moderate in one of four tested melted corneas. Casein zymography revealed no presence of MMP 3 or 7 in any control cornea. A moderate to strong presence of MMP 7 proenzyme was detected in all four melted corneas. Active MMP 1 was detected in all four melted corneas, whereas the controls were negative.
Conclusions: :
The increased presence and activity of MMP 1, 2, and 9 in melted corneal grafts suggest that these enzymes may be responsible for the destruction of the extracellular matrix seen in grafts undergoing corneal melting.
Keywords: cornea: basic science • cornea: stroma and keratocytes • transplantation