PLASMINOGEN-ACTIVATOR INHIBITOR-1 OVEREXPRESSION IN NONPROLIFERATIVE DIABETIC-RETINOPATHY

Plasminogen activator inhibitor-1 is secreted bidirectionally by endot helial cells, acts as the primary regulator of fibrinolysis and as a k ey modulator of extracellular matrix proteolysis. Elevated serum level s of plasminogen activator inhibitor-1 are observed in serum of diabet ic individuals. We investigated whether plasminogen activator inhibito r-1 is overexpressed in capillaries of diabetic donors with nonprolife rative retinopathy compared to nun-diabetic donors. We also assessed p lasminogen activator inhibitor-1 expression in an animal model of reti nopathy induced by exposing rabbit retinas to insulinlike growth facto r-1. Colloidal gold immunocytochemistry was used to quantify plasminog en activator-1 antigen in donor retinas from diabetic subjects (n = 10 ) and control subjects (n = 10). This technique was also used to exami ne expression of plasminogen activator inhibitor-1 for correlation wit h retinal changes in the insulin-like growth factor-I-induced retinopa thy model (n = 14). Plasminogen activator inhibitor-1 immunoreactivity was significantly increased in the retinas of all diabetic subjects a s compared to controls. In the rabbit model, the expression of plasmin ogen activator inhibitor-1 immunoreactivity correlated with pathologic al retinal changes. In both the diabetic human and insulinlike growth factor-I-injected rabbit, overproduction of plasminogen activator inhi bitor-1 was seen within the lumen of capillaries, within the cytoplasm of endothelial cells and in the basement membrane and extracellular m atrix surrounding these capillaries. Minimal plasminogen activator inh ibitor-1 was detected in the retinas of non-diabetics and in control r abbits injected with either heat-inactivated insulin-like growth facto r-I or balanced salt solution, These studies support the conclusion th at plasminogen activator inhibitor-1 is overexpressed in the retinal c apillaries of diabetics with nonproliferative diabetic retinopathy and in rabbits with insulin-like growth factor-I-induced retinopathy. (C) 1996 Academic Press Limited