The significance of vitronectin in proliferative diabetic retinopathy

Abstract

Vitronectin, an integrin-binding a-1-glycoprotein with potent cell-adhesion and proliferation-mediating properties, has been shown to be incorporated in surgically removed membranes from patients with proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR) and macular pucker. Therefore we developed an ELISA technique to quantify levels of vitronectin in human vitreous and plasma samples in order to be able to evaluate the significance of vitronectin in these different vitreoretinal diseases. Our results indicate a significant increase of vitronectin in all proliferative disorders except idiopathic macular pucker. Adjustment of all probes to equal total protein content yielded a significant increase only in PDR (type II diabetes). Plasma samples demonstrated a significant increase of vitronectin in patients with type II diabetes suffering from PDR. Therefore, break-down of the blood-retina barrier appears to be the most likely explanation for the increased levels of vitronectin in the vitreous. Our results indicate that vitronectin may not only be involved in the regulation of epiretinal membrane formation at significantly higher levels in patients with type II diabetes, but the increase of vitronectin in diabetic plasma may also help to explain the pathological alteration of the coagulation cascade in diabetics.

Induction of Posterior Vitreous Detachment in Rabbits by Intravitreal Injection of Tissue Plasminogen Activator Following Cryopexy

“…Vitronectin levels were increased three-fold compared to untreated controls but were 500-1000-fold less than those estimated in diabetic eyes of idiopathic PVR (Esser et al, 1994). The source of elevated vitronectin is sufficiently explained by the temporary breakdown of the blood-retina barrier after cryopexy.…”

“…Finally we measured vitronectin, a glycoprotein with proliferation-mediating properties, that is significantly increased in proliferative retinal disorders (Casaroli Marano and Vilaro, 1994 ;Esser et al, 1994). Vitronectin levels were increased three-fold compared to untreated controls but were 500-1000-fold less than those estimated in diabetic eyes of idiopathic PVR (Esser et al, 1994).…”

Diabetes Mellitus, Glycoprotein IIb/IIIa Blockade, and Heparin

“…It is unlikely that this effect is explained by gross differences in heparin metabolism because the ACT responses indicate that similar levels of anticoagulation were achieved with similar doses of heparin in diabetics and nondiabetics. A variety of other perturbations have been reported in the coagulation systems of diabetic patients that might affect platelet function, including larger platelets, 8 greater expression of P-selectin, 14 higher platelet surface density of GP IIb/IIIa, 8,9 altered thromboxane metabolism, 15 and higher levels of circulating fibrinogen, 10 vitronectin, 16,17 and thrombin-antithrombin III complexes, 18 as well as more extensive endothelial dysfunction. 19,20 Diabetic patients also have higher mortality in the acute coronary syndromes 21 and in general have more extensive coronary artery disease than do nondiabetics.…”

Levels of pentosidine in the vitreous of eyes with proliferative diabetic retinopathy, proliferative vitreoretinopathy and retinal detachment

“…These results could simply reflect the breakdown of the blood-retinal barrier, a common component of the pathophysiology of PDR, PVR and RD [2,3,12,22,23]. The alteration of the blood-retinal barrier was also suggested to account for increased levels of other proteins (IgG, complement factor C4, vitronectin) in the vitreous cavity of patients with PVR [4,7]. Also, insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein 2 (IGFBP-2) and IGFBP-3 were shown to be elevated in the vitreous of patients with PDR due to the influx of serum proteins [14].…”