[Experimental study on effects of matrix metalloproteinase inhibitor on posterior capsule opacification in rabbits].

OBJECTIVE: To determine whether matrix metalloproteinase (MMP) inhibitor can provide therapeutic effects for rabbits posterior capsule opacification in vivo and to observe the side effects of this drug on surrounding intraocular structures. METHODS: Experimental research. New Zealand white rabbits were undertaken phacoemulsification operation. GM6001 at different concentrations (100, 200 and 500 µmol/L) and GM6001 negative control liqueur were infused into the capsule bags of the rabbits at the end of operation and two days after the operation. The incidence of posterior capsule opacification was assessed and the histological sections of posterior capsules were observed under microscope 12 weeks after the surgery. The anterior chamber response was observed on day 2 post-operatively. The changes of intraocular pressure were measured by day 2 and day 7. Corneal endothelial cells were observed under scanning electron microscope and iris, ciliary body and retina were observed under microscope on day 7. RESULTS: GM6001 significantly prevented posterior capsule opacification (P = 0.007). No opacification occurred on the rabbit posterior capsule in eyes with 200 and 500 µmol/L GM6001 on week 12 post-operatively in vivo. No cells were found on posterior capsule in 500 µmol/L group, whereas lens epithelial cells and fibroblasts were found in the controls under microscope. No difference of anterior chamber flare between the eyes with GM6001 at different concentrations and the control group (P = 0.380) by day 2 after the operation. The intraocular pressure in eyes with GM6001 was the same as that in the control 2-days (F = 0.642, P = 0.597) and 7-days (F = 0.179, P = 0.909) post-operation. The corneal endothelial cells in eyes with 500 µmol/L GM6001 arranged regularly and did not show any difference from that in the control eyes under scanning electron microscope 7-day after the operation. The iris, ciliary body and retina in eyes with 500 µmol/L GM6001 were normal in appearance 7-day after the operation. CONCLUSIONS: MMP inhibitor can prevent posterior capsule opacification effectively in rabbits in vivo and does not cause damage to surrounding intraocular structures, suggesting that MMP inhibitor may become a medication used for the prevention of lens posterior capsule opacification.

Effect of hydroxamic acid-based matrix metalloproteinase inhibitors on human gingival cells and Porphyromonas gingivalis.

BACKGROUND: Matrix metalloproteinases (MMPs) are considered to play key roles in tissue destruction during periodontitis. In this study, we evaluated the cytotoxicity of hydroxamic acid-based MMP inhibitors (ONO-4817, ONO-MI1-514, and ONO-MI1-570), and their inhibitory effects on MMP-2 and -9 activities and growth of Porphyromonas gingivalis. METHODS: Human gingival fibroblasts (HGF) and human gingival epithelial cells (HGE) were incubated with test inhibitors prior to investigating cell viability, cell proliferation, and mRNA expression for MMP-2 and -9. Gelatin zymography and a colorimetric MMP assay were performed to study the inhibitory effects on MMP-2 and -9 activities derived from HGF and HGE, respectively. The effect of MMP inhibitors on keratinocyte migration and P. gingivalis growth was also tested. RESULTS: Cell viability was not affected by any of the inhibitors at a final concentration of 50 microM, nor was cell proliferation at 20 microM. All inhibitors clearly inhibited MMP-2 produced by HGF and MMP-9 produced by HGE in a dose-dependent manner. No change was found in mRNA expression of MMPs by gingival cells treated with the inhibitors. ONO-4817 and ONO-MI1-514 inhibited keratinocyte migration. ONO-4817 showed a slightly inhibitory effect on the growth of P. gingivalis. CONCLUSION: Data obtained in this study support the potential use of the three MMP inhibitors for the prevention and treatment of periodontal disease.