Plasma vascular endothelial growth factor, angiopoietin-2, and soluble angiopoietin receptor tie-2 in diabetic retinopathy: effects of laser photocoagulation and angiotensin receptor blockade.
BACKGROUND
Proliferative diabetic retinopathy (PDR) may be a response to abnormal angiogenic growth factors such as vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), and the soluble angiopoietin receptor tie-2. The authors hypothesised the following: (a) there are differences in plasma levels of these growth factors in different grades of diabetic retinopathy; and (b) that the effects of intervention with panretinal laser photocoagulation (PRP) for PDR, and angiotensin receptor blockade (using eprosartan) for patients with other grades of diabetic retinopathy will be to reduce levels of the growth factors.


METHODS
Cross sectional and interventional study (using PRP and eprosartan) in diabetic patients. VEGF, Ang-2, and tie-2 were measured by ELISA.


RESULTS
VEGF (p<0.001) and Ang-2 levels (p<0.001) were significantly higher in 93 diabetic patients compared to 20 healthy controls, with the highest levels in grade 2 and grade 3 diabetic retinopathy (p<0.05). Tie-2 was lower in diabetics compared to controls (p = 0.008), with no significant differences between the diabetic subgroups. Overall, VEGF significantly correlated with Ang-2 (p<0.001) and tie-2 (p = 0.004) but the correlation between Ang-2 and tie-2 levels was not significant (p = 0.065). Among diabetic patients only, VEGF levels were significantly correlated with Ang-2 (p<0.001) and tie-2 (p<0.001); the correlation between Ang-2 and tie-2 levels was also significant (p<0.001). There were no statistically significant effects of laser photocoagulation on plasma VEGF, Ang-2, and tie-2 in the 19 patients with PDR, or any effects of eprosartan in the 28 patients with non-proliferative diabetic retinopathy.


CONCLUSIONS
Increased plasma levels of VEGF and Ang-2, as well as lower soluble tie-2, were found in diabetic patients. The highest VEGF and Ang-2 levels were seen among patients with pre-proliferative and proliferative retinopathy, but there was no relation of tie-2 to the severity of retinopathy. As the majority of previous research into Ang-2 and tie-2 has been in relation to angiogenesis and malignancy, the present study would suggest that Ang-2 and tie-2 may be used as potential indices of angiogenesis in diabetes mellitus (in addition to VEGF) and may help elucidate the role of the angiopoietin/tie-2 system in this condition.
Lip
P L
PL
University Department of Medicine, City Hospital, Birmingham B18 7QH, UK. g.y.h.lip@bham.ac.uk
Chatterjee
S
S
Caine
G J
GJ
Hope-Ross
M
M
Gibson
J
J
Blann
A D
AD
Lip
G Y H
GY
D000179:Acrylates / Q000627:therapeutic use; D042702:Angiopoietin-2 / Q000097:blood*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists; D003430:Cross-Sectional Studies; D003930:Diabetic Retinopathy / Q000097:blood* / Q000188:drug therapy / Q000601:surgery; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D017075:Laser Coagulation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D042787:Receptor, TIE-2 / Q000097:blood*; D013876:Thiophenes / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D000179:Acrylates; D042702:Angiopoietin-2; D047228:Angiotensin II Type 1 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D013876:Thiophenes; D042461:Vascular Endothelial Growth Factor A; C068373:eprosartan; D042787:Receptor, TIE-2