Human diabetic neovascular membranes contain high levels of urokinase and metalloproteinase enzymes

PURPOSE. Retinal neovascularization is one of the leading causes of blindne ss. A crucial event in this process is the remodeling and penetration of th e capillary basement membrane by migrating endothelial cells. This process requires proteolysis of basement membrane components by a variety of protei nases. The objective of the present study was to determine the expression o f proteinases in human retinal tissues showing active neovascularization. METHODS. Epiretinal neovascular membranes surgically removed from patients with proliferative diabetic retinopathy were analyzed by zymography, and th e types and amounts of proteinases present in the tissues were determined. Retinas from nondiabetic donor eyes served as control specimens. RESULTS. Both the high- (54 kDa) and low- (33 kDa) molecular-weight forms o f urokinase were present at significantly higher levels in neovascular memb ranes than in normal retinas. The pro forms of the matrix metalloproteinase s (MMP) MMP-2 and MMP-9 were significantly elevated in the neovascular memb ranes in comparison with levels in normal retinas. In addition, the active forms of these enzymes were present in the membranes, whereas there was no detectable level of the active forms in normal retinas. CONCLUSIONS. Human diabetic neovascular membranes contain high levels of ur okinase and MMP. The increased activity of proteinases in the final common pathway of retinal neovascularization indicates that inhibition of these en zymes may be a useful therapeutic target as an alternative approach in the management of proliferative retinopathies.