Study on inhibitory effects of matrix metalloproteinase inhibitor on migration of cultured human lens epithelial cells

Abstract

To determine whether matrix metalloproteinases inhibitor can prevent human lens epithelial cell migration in lens capsule bag model from the donor eyes. This study was an experimental investigation. Sham cataract surgery were performed in 16 human donor eyes. The donor lens capsule bags were cultured and treated with a broad MMP inhibitor (GM6001) at different concentrations (1, 10 and 100 micromol/L) and without GM6001 (negative control). The distance of lens epithelial cells migration on the posterior capsule was measured in all capsule bags under microscope and total MMP-2 and MMP-9 protein production was determined by ELISA. The cell viability in all groups was determined using methylthiazol tetrazolium (MTT) test. Lens epithelial cells at the equator began to migrate by day 4. Epithelial cells migration onto the posterior capsule was significantly reduced by GM6001 in a dose dependent manner as compared with the controls (F = 53.79, P < 0.01). Seventy percent reduction (P < 0.01) and 98% reduction (P <0. 01) of migration were observed in 10 micromol/L and 100 micromol/L GM6001 treated cultures, respectively, as compared with that in control on day 20. MMP levels in capsular bag were reduced by GM6001, the greatest inhibitory effect was found at the highest concentrations of GM6001 (F = 86.59,72.96; P < 0.01). By day 20, the reduction in total MMP-2 level (P < 0.01) and MMP-9 level (P < 0.01) in 10 micromol/L GM6001 treated cultures was 70% as compared with that in control. Ninety percent reduction in MMP-2 level (P < 0.01) and 87% reduction in MMP-9 level (P < 0.01) were found in 100 micromol/L GM6001 treated cultures. Lens epithelial cells remained viable and proliferated in the presence of all concentrations of GM6001. No significant difference of cell viability between the controls and GM6001 treated cultures (1,10, and 100 micromol/L) was found by the MTT assay (F = 0.62, P > 0.05). MMP inhibitor inhibits the lens epithelial cell migration onto the posterior capsule and does not affect the cell viability in cultured lens capsule bags in vitro. Therefore, MMP inhibition may have a role in the treatment of posterior capsule opacification.