Elsevier

Ophthalmology

Volume 115, Issue 11, November 2008, Pages 1916-1922
Ophthalmology

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

https://doi.org/10.1016/j.ophtha.2008.06.025Get rights and content

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 = 27] vs 1568.8±595.0 pg/mL [n = 12, P = 0.009]) and VEGF (1316.2±404.6 pg/mL [n = 27] 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.

Section snippets

Materials

Enzyme-linked immunosorbent assay (ELISA) kits for human sVEGFR-1 (Quantikine Human soluble VEGF R1/Flt-1 Immunoassay), human VEGF (Endogen Human VEGF), and PEDF (ChemiKine PEDF) were purchased from R&D Systems (Minneapolis, MN), Pierce Biotechnology Inc (Rockford, IL), and Chemicon (Temecula, CA), respectively. sVEGFR-1 and angiogenesis kits were purchased from Fitzgerald (Concord, MA) and Kurabo (Osaka, Japan), respectively.

Preparation of Vitreous Fluid Samples

This study was conducted according to the tenets of the Declaration

sVEGFR-1, VEGF, and PEDF levels in Vitreous Fluids of Patients with MH or PDR

We measured the concentrations of sVEGFR-1, VEGF, and PEDF in vitreous fluids obtained from patients with MH or PDR. The concentration of sVEGFR-1 was significantly higher in patients with PDR (3949.4±608.9 pg/mL, n = 27) than in patients with MH (1568.8±595.0 pg/mL, n = 12) (P = 0.009) (Fig 1A), as was that of VEGF (PDR, 1316.2±404.6 pg/mL [n = 27]; MH, 11.7±8.1 pg/mL [n = 12]) (P = 0.003) (Fig 1B). For statistical analysis, any VEGF level below the limit of detection was set to zero. Next, we

Discussion

In the present study, we investigated the level of sVEGFR-1 in vitreous fluid samples taken from patients with PDR or MH. Our first finding was that the vitreous concentration of sVEGFR-1 was significantly higher in eyes with PDR than in those with MH. We also found a significantly positive correlation between the sVEGFR-1 and VEGF concentrations in vitreous fluids from patients with PDR. In the vitreous fluid of PDR eyes, our results indicate that the higher level of VEGF may lead to an

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    Manuscript no. 2008-293.

    Financial Disclosure(s): The authors have no proprietary or commercial interests in any materials discussed in this article.

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