The angiopoietin/Tie-2 system in proliferative sickle retinopathy: relation to vascular endothelial growth factor, its soluble receptor Flt-1 and von Willebrand factor, and to the effects of laser treatment.
OBJECTIVE
To determine plasma levels of angiopoietin-1 and angiopoietin-2 (Ang-1, Ang-2), their soluble receptor Tie-2, vascular endothelial growth factor (VEGF), its soluble receptor Flt-1 (as indices of angiogenesis), and von Willebrand factor (vWf, marking endothelial damage/dysfunction) in sickle cell disease (SCD) patients with proliferative sickle retinopathy (PSR), with non-proliferative retinopathy (NPR), or no retinopathy (NR) and in control subjects with normal haemoglobin (AA subjects). In addition, to determine changes with panretinal laser photocoagulation (PRP) therapy.


METHODS
Research indices were measured (ELISA) in 24 SCD patients who had PSR, 16 with NPR, 16 with NR, and from 23 AA subjects. Eight patients received PRP therapy and plasma was obtained before laser treatment and at 6 months after the last PRP session.


RESULTS
Ang-1, Ang-2, VEGF, and vWf (but not Tie-2 or sFlt-1) were raised in SCD patients compared to AA subjects (p<0.01) but there were no differences among the three SCD subgroups. Significant correlations were between Ang-1 and VEGF, Ang-1 and Tie-2, and VEGF and sFlt-1 in patients with SCD (r = 0.67-0.88). Plasma Ang-2, VEGF, sFlt-1, and vWf levels did not change, but Ang-1 fell and Tie-2 rose significantly following PRP therapy.


CONCLUSIONS
SCD patients have raised plasma angiopoietins (Ang-1, Ang-2), VEGF, and vWf compared to AA subjects. These indices did not differ according to severity of retinopathy and only limited changes occurred following PRP. The elevated growth factor levels in SCD may have obscured any association with retinopathy.
Mohan
J S
JS
Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, The Birmingham and Midland Eye Centre, City Hospital, UK.
Lip
P L
PL
Blann
A D
AD
Bareford
D
D
Lip
G Y H
GY
D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000601:surgery; D042683:Angiopoietin-1 / Q000097:blood; D042702:Angiopoietin-2 / Q000097:blood; D042682:Angiopoietins / Q000097:blood; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D017075:Laser Coagulation / Q000379:methods; D008297:Male; D042787:Receptor, TIE-2 / Q000097:blood; D012164:Retinal Diseases / Q000097:blood* / Q000601:surgery; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood; D014841:von Willebrand Factor / Q000032:analysis
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D042682:Angiopoietins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor; D042787:Receptor, TIE-2; D040281:Vascular Endothelial Growth Factor Receptor-1