Angiotensin converting enzyme inhibiting therapy is associated with lower vitreous vascular endothelial growth factor concentrations in patients with proliferative diabetic retinopathy

• Published in: Diabetologia 2002-02, Vol.45 (2), p.203-209
• Main Authors: HOGEHOOM VAN BUGGENUM, I. M, POLAK, B. C. P, REICHERT-THOEN, J. W. M, DE VRIES-KNOPPERT, W. A. E. J, VAN HINSBERGH, V. W. M, TANGELDER, G. J
• Format: Article
• Language: English
• Subjects: Adult; Age of Onset; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Biological and medical sciences; Blood Pressure - drug effects; Diabetes Mellitus, Type 1 - physiopathology; Diabetes Mellitus, Type 2 - physiopathology; Diabetic Retinopathy - physiopathology; Enalapril - therapeutic use; Endothelial Growth Factors - metabolism; Female; Humans; Intraocular Pressure - drug effects; Lymphokines - metabolism; Male; Middle Aged; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Vitreous Body - blood supply; Vitreous Body - drug effects; Vitreous Body - physiology
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-001-0747-8

Vascular endothelial growth factor (VEGF) is thought to be instrumental in the progression of diabetic retinopathy. Indications exist that the renin-angiotensin system is involved in VEGF overexpression. We assessed the vitreous VEGF concentrations in patients and related them to anti-hypertensive treatment, with special interest in the use of ACE-inhibitors. Samples of vitreous fluid (10-80 microl) were obtained from 39 patients both with Type I (insulin-dependent) and Type II (non-insulin-dependent) diabetes mellitus and 11 non-diabetic patients undergoing intra-ocular surgery. The VEGF-A concentrations were assessed by immunoassay. Control patients and patients without proliferative diabetic retinopathy ( n = 8) had low and comparable VEGF concentrations (medians < 50 pg/ml). In contrast, patients with proliferative diabetic retinopathy ( n = 31) had high vitreous VEGF concentrations (median 1134 pg/ml), which showed a negative correlation with the use of ACE inhibiting medication (Spearman rank-R = - 0.54; p = 0.002, n = 13). Diastolic and systolic blood pressure did not differ significantly between the two subgroups with proliferative diabetic retinopathy, i. e. those patients receiving ACE-inhibition (medians 88/160 mm Hg, respectively) and the others (90/160). For the mostly used ACE-inhibitor in the proliferative diabetic retinopathy group, i. e. enalapril ( n = 8), a linear dose-effect relation was observed (-20 +/- 4 pg x ml(-1) x mg(-1) x day(-1); p = 0.024; coefficient +/- SEM). Treatment with ACE-inhibitors attenuates retinal overexpression of VEGF-A in patients with proliferative diabetic retinopathy, probably by interference with a local effect of angiotensin II.