Role of soluble vascular endothelial growth factor receptor-1 in the vitreous in proliferative diabetic retinopathy.
OBJECTIVE
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).


METHODS
Retrospective case-control study.


METHODS
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.


METHODS
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.
Matsunaga
Nozomu
N
Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
Chikaraishi
Yuichi
Y
Izuta
Hiroshi
H
Ogata
Nahoko
N
Shimazawa
Masamitsu
M
Matsumura
Miyo
M
Hara
Hideaki
H
D000368:Aged; D020533:Angiogenesis Inhibitors / Q000502:physiology*; D016022:Case-Control Studies; D018920:Coculture Techniques; D003930:Diabetic Retinopathy / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000517:prevention & control*; D009414:Nerve Growth Factors / Q000378:metabolism; D012167:Retinal Perforations / Q000378:metabolism; D012189:Retrospective Studies; D015843:Serpins / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000502:physiology*; D014822:Vitreous Body / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor
D020533:Angiogenesis Inhibitors; D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D000099174:Pigment Epithelium-Derived Factor; C467484:VEGFA protein, human