We examined the effect of
matrix metalloproteinase (
MMP) inhibitor (CS-610) on experimental pseudomonal corneal ulceration by clinical and histological evaluation. Intrastromal injection of 3.5 microliters sterile culture broth of P. aeruginosa, IID-1117 (13.5 unit Type I
collagenase equivalent
proteinase activities), was done to induce corneal
ulcers in guinea pigs. The animals were divided into two groups of 23 each. The
CS-610 group received topical
CS-610 (400 micrograms/ml) treatment at 2-hour intervals and the control group received only the vehicle of
CS-610 at the same intervals. In the control group, corneas developed acute
corneal damage following corneal ulcerations at 6-12 hours. In the
CS-610 group, these corneal lesions were inhibited in most of the eyes (p < 0.01). In the late period, as inflammatory cells migrated into the cornea, some animals of the
CS-610 group developed
corneal ulcer. The results indicated that
CS-610 had a potent inhibitory activity against pseudomonal
proteinases in vivo. The results also suggested that the mechanism of the ulceration model involved not only pseudomonal
proteinases but also endogenous responses.