Role of Soluble Vascular Endothelial Growth Factor Receptor-1 in the Vitreous in Proliferative Diabetic Retinopathy

Purpose: To determine the vitreous level of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) in patients with proliferative diabetic retinopathy (PDR) or idiopathic macular hole (MH). Furthermore, to investigate the relationships among sVEGFR-1, vascular endothelial growth factor (VEGF), and pigment epithelium-derived factor (PEDF). Design: Retrospective case-control study. Participants: Thirty-eight patients who underwent vitrectomy (PDR [27 eyes in 26 patients] or MH [12 eyes in 12 patients]). Methods: In vitreous fluid samples obtained during vitreoretinal surgery, sVEGFR-1, VEGF, and PEDF levels were measured by enzyme-linked immunosorbent assay. Effects of sVEGFR-1 on VEGF-A-induced tube formation were investigated using human umbilical vein endothelial cells co-cultured with fibroblasts. Main Outcome Measures: Levels of sVEGFR-1 and the relationships among sVEGFR-1, VEGF, and PEDF in vitreous fluids from patients with PDR or MH. Results: In PDR (vs MH), there were significantly higher vitreous concentrations of both sVEGFR-1 (3949.4 +/- 608.9 pg/mL [mean standard error, n = 271 vs 1568.8 +/- 595.0 pg/mL [n = 12, P = 0.009]) and VEGF (1316.2 +/- 404.6 pg/mL [n = 271 vs 11.7 +/- 8.1 pg/mL [n = 12, P = 0.003]), whereas the vitreous concentration of PEDF was significantly lower (2.1 +/- 1.1 ng/mL [n = 27] vs 41.6 +/- 17.0 ng/mL [n = 12, P = 0.041]). In PDR, there was a significant positive correlation between the sVEGFR-1 and VEGF vitreous concentrations (r = 0.414, P 0.032), but not between PEDF and VEGF (r = 0.196, P = 0.328) or between sVEGFR-1 and PEDF (r = 0.167, P = 0.406). In vitro, sVEGFR-1 (0.1-1000 ng/mL) concentration-dependently inhibited VEGF-A-induced tube formation, its effect being significant at 100 to 1000 ng/mL on the tube area, length, and path. Conclusions: In the vitreous fluids of patients with PDR, the sVEGFR-1 level was increased (vs that in patients with MH), and sVEGFR-1 correlated significantly with VEGF. In vitro, sVEGFR-1 reduced VEGF-induced angiogenesis. Thus, sVEGFR-1 may play a pivotal antiangiogenic role in PDR. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2008;115:1916-1922 (C) 2008 by the American Academy of Ophthalmology.