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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Hogeboom van Buggenum
I M
IM
Department of Ophthalmology, Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands.
Polak
B C P
BC
Reichert-Thoen
J W M
JW
de Vries-Knoppert
W A E J
WA
van Hinsbergh
V W M
VW
Tangelder
G J
GJ
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000503:physiopathology*; D004656:Enalapril / Q000627:therapeutic use*; D016228:Endothelial Growth Factors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014822:Vitreous Body / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D004656:Enalapril