Purpose: In angiogenesis, matrix degradation is an important step in endothelial cell migration and proliferation. There is evidence that serine proteases, such as tissue plasminogen activator (TPA), urokinase-type plasminogen activator (UPA), and plasminogen activator inhibitor (PAI), are involved in this process. We hypothesized that in eyes in which neovascularization is active, such as in proliferative diabetic vitreoretinopathy (PDVR), vitreous levels of these proteases are increased. Furthermore, correlation was sought between intraocular concentrations of serine proteases and vascular endothelial growth factor (VEGF), a multifunctional cytokine that has been shown to play a major part in mediating active neovascularization in patients with ischemic retinal diseases.
Methods: Undiluted samples of vitreous fluid were obtained from patients who underwent vitreoretinal surgery for PDVR or retinal detachment. Vitreous levels of VEGF, TPA, UPA, and PAI were determined by enzyme-linked immunosorbent assay.
Results: We found a statistically significant correlation between levels of VEGF and TPA (P<0.01) and VEGF and PAI (P<0.026) in the vitreous fluid of patients with PDVR. Concentrations of VEGF (P<0.03), TPA (P<0.042), and PAI (P<0.0098) in diabetic eyes were significantly higher than in nondiabetic eyes. Of 14 eyes with PDVR, 6 contained detectable levels of UPA.
Conclusions: A correlation between increased levels of VEGF and TPA or PAI in the vitreous fluid of eyes with PDVR reflects the possible role of plasminogen activators in the progression of this disease. An understanding of the endogenous inhibition of matrix degradation in ocular angiogenesis may be useful in the development of new treatment strategies.