Correlation Between the Activity of Angiotensin–Converting Enzyme and The Levels of Neovascularization Promoting Factors in the Vitreous Fluid of Diabetic Retinopathy

Abstract

Abstract: : Purpose:AngiotensinII induces the expression of neovascularization promoting factors such as vascular endothelial growth factor (VEGF) ,matrix metalloproteinases (MMP)–2 and MMP–9. However, it remains unclear about the relation in diabetic retinopathy (DR). To investigate the correlation between the concentrations of VEGF, MMP–2, MMP–9 and the activity of angiotensin–converting enzyme (ACE) , which is the angiotensinII–forming enzyme in the vitreous fluid of patients with diabetic retinopathy. Methods:Vitreous samples were collected during vitreous surgery from 35 eyes of patients with DR, and from 7 eyes of patients with idiopathic macular hole(MH), who served as a control. The activity of ACE was measured by high pressure liquid chromatography (HPLC). The VEGF concentration was measured by enzyme–linked immunosorbent assay (ELISA). The MMP–2 and MMP–9 concentrations were measured by enzyme immunoassay(EIA). Results:The activity of ACE (P<0.0001) and levels of VEGF (P=0.001) and MMP–9 (P<0.05) were significantly higher in patients with DR than in MH. There were no significant differences about the level of MMP–2. The activity of ACE was significantly correlated with the level of VEGF (P<0.01,r=0.52), MMP–2 (P=0.01,r=0.46), and MMP–9 (P=0.001,r=0.48). The level of VEGF was significantly correlated with the level of MMP–9 (P=0.001,r=0.56), but not with that of MMP–2. Conclusions: The activity of ACE and the levels of VEGF and MMP–9 were significantly elevated in the vitreous fluid of DR. In addition, the activity of ACE and the levels of VEGF and MMP–9 were significantly correlated with each other. These findings indicate that the elevation of ACE contributes to the neovascularization in DR through the induction of the expression of VEGF and MMP–9.

Keywords: diabetic retinopathy • retinal neovascularization • vitreous