Tissue factor increases in the aqueous humor of proliferative diabetic retinopathy

Background: Tissue factor (TF) is a cellular initiator of the co-agulation cascade and is upregulated by the major factors of diabetic angiopathy, TF might thus be one of the key molecules in diabetic retinopathy (DR). Purpose: To measure TF in diabetic eyes and evaluate its possible role in DR. Methods: TF concentration in the aqueous humor of the eyes in 44 patients with diabetes and 35 age-matched control patients was evaluated by ELISA. The concentration of TF in aqueous humor (AH) was compared with the grade of DR. The concentration of TF in AH was also compared with duration of diabetes, renal function, and blood glucose control. The serum TF concentration in each group was also compared. The correlation between the serum TF and aqueous TF in each patient was analyzed. The effect of vascular endothelial growth factor (VEGF) on the TF activity of cultured bovine retinal endothelial cells was evaluated. Results: The mean TF concentration in AH was higher in patients with active proliferative DR (244.5 pg/ml) than in either those with non-proliferative DR (132.4 pg/ml, P<0.05) or the control patients (114.9 pg/ml, P<0.01). The serum TF concentration in active proliferative DR patients (348.3 pg/ml) was significantly higher than in either non-proliferative DR patients, (235.9 pg/ml, P<0.01) or in the controls (223.5 pg/ml, P<0.01). However, the TF concentration of AH was not significantly correlated to that of the serum in each patient. The TF concentration in AH closely correlated with the grade of DR and protein concentration. VEGF increased the biological activity of TF in vitro. Conclusion: The origin of TF in AH, however, is still not clearly understood. Nonetheless, TF in AH directly reflects the severity of ocular diabetic change, and the present results indicate that TF indeed plays some role in the progression of DR.