SCIENTIFIC REPORT

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

J S Mohan^1,2, P L Lip³, A D Blann¹, D Bareford² and G Y H Lip¹

¹ Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, The Birmingham and Midland Eye Centre, City Hospital, Birmingham B18 7QH, UK
² Department of Haematology, The Birmingham and Midland Eye Centre, City Hospital, Birmingham B18 7QH, UK
³ Department of Ophthalmology, The Birmingham and Midland Eye Centre, City Hospital, Birmingham B18 7QH, UK

Correspondence to:
Correspondence to:
Professor G Y H Lip
University Department of Medicine, City Hospital, Birmingham B18 7QH, UK; g.y.h.lip{at}bham.ac.uk

Aim: 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.

Abbreviations: Ang, angiopoietin; HbS, sickle haemoglobin; HPLC, high performance liquid chromatography; NPR, non-proliferative retinopathy; NR, no retinopathy; PRP, panretinal laser photocoagulation; PSR, proliferative sickle retinopathy; SCD, sickle cell disease; VEGF, vascular endothelial growth factor; vWf, von Willebrand factor

Keywords: proliferative sickle retinopathy; vascular endothelial growth factor; von Willebrand factor; sickle cell disease

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