Plasminogen Activator Inhibitor-1 Overexpression in Nonproliferative Diabetic Retinopathy

• Published in: Experimental eye research 1996-09, Vol.63 (3), p.233-244
• Main Authors: GRANT, MARIA B., ELLIS, E.ANN, CABALLERO, SERGIO, MAMES, ROBERT N.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Animals; Associated diseases and complications; Basement Membrane - metabolism; Biological and medical sciences; Capillaries - metabolism; Diabetes. Impaired glucose tolerance; diabetic retinopathy; Diabetic Retinopathy - metabolism; Diabetic Retinopathy - pathology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Extracellular Matrix - metabolism; Female; Humans; immunocytochemistry; Immunohistochemistry; insulin-like growth factor-I; Male; Medical sciences; Microscopy, Electron; Middle Aged; plasminogen activator inhibitor; Plasminogen Activator Inhibitor 1 - analysis; Plasminogen Activator Inhibitor 1 - metabolism; Rabbits; retinal endothelial cells
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1006/exer.1996.0112

Plasminogen activator inhibitor-1 is secreted bidirectionally by endothelial cells, acts as the primary regulator of fibrinolysis and as a key modulator of extracellular matrix proteolysis. Elevated serum levels of plasminogen activator inhibitor-1 are observed in serum of diabetic individuals. We investigated whether plasminogen activator inhibitor-1 is overexpressed in capillaries of diabetic donors with non-proliferative retinopathy compared to non-diabetic donors. We also assessed plasminogen activator inhibitor-1 expression in an animal model of retinopathy induced by exposing rabbit retinas to insulin-like growth factor-I. Colloidal gold immunocytochemistry was used to quantify plasminogen activator-1 antigen in donor retinas from diabetic subjects ( n=10) and control subjects ( n=10). This technique was also used to examine expression of plasminogen activator inhibitor-1 for correlation with retinal changes in the insulin-like growth factor-I-induced retinopathy model ( n=14). Plasminogen activator inhibitor-1 immunoreactivity was significantly increased in the retinas of all diabetic subjects as compared to controls. In the rabbit model, the expression of plasminogen activator inhibitor-1 immunoreactivity correlated with pathological retinal changes. In both the diabetic human and insulin-like growth factor-I-injected rabbit, overproduction of plasminogen activator inhibitor-1 was seen within the lumen of capillaries, within the cytoplasm of endothelial cells and in the basement membrane and extracellular matrix surrounding these capillaries. Minimal plasminogen activator inhibitor-1 was detected in the retinas of non-diabetics and in control rabbits injected with either heat-inactivated insulin-like growth factor-I or balanced salt solution. These studies support the conclusion that plasminogen activator inhibitor-1 is overexpressed in the retinal capillaries of diabetics with non-proliferative diabetic retinopathy and in rabbits with insulin-like growth factor-I-induced retinopathy.