Extracellular SOD and VEGF are increased in vitreous bodies from proliferative diabetic retinopathy patients.
OBJECTIVE
To evaluate the relationship between vascular endothelial growth factor (VEGF) and extracellular superoxide dismutase (EC-SOD) in vitreous body and serum in patients with proliferative diabetic retinopathy (PDR), and investigate the role of EC-SOD in PDR by evaluating its angiostatic effect, using an in vitro angiogenesis model. To investigate the role of EC-SOD in PDR by evaluating its angiostatic effect, using an in vitro angiogenesis model.


METHODS
EC-SOD and VEGF concentrations in vitreous and serum samples from PDR and macular hole (MH) were measured by ELISA. The effects of EC-SOD on VEGF-induced proliferation, migration, and tube formation were evaluated using human umbilical vein endothelial cells (HUVECs). Moreover, the effects of EC-SOD on VEGF-induced proliferation and migration were evaluated in HUVECs and primary normal human retinal microvascular endothelial cells.


RESULTS
Intravitreal concentrations of EC-SOD were significantly higher (p<0.01) in PDR (58.0+/-23.8 ng/ml, mean+/-SD) than in MH (29.3+/-6.6 ng/ml). Intravitreal concentrations of VEGF were dramatically higher (p<0.01) in PDR (798.2+/-882.7 pg/ml) than in MH (17.7+/-15.5 pg/ml). The serum concentrations of EC-SOD and VEGF did not differ between the two patient groups. The vitreous concentrations of VEGF correlated with those of EC-SOD in all patients (rs=0.61, p<0.001). In HUVECs, EC-SOD at 100 ng/ml significantly suppressed VEGF-induced proliferation and tube formation, but not VEGF-induced migration.


CONCLUSIONS
EC-SOD was increased together with VEGF in the vitreous body from PDR patients, suggesting that EC-SOD may play a pivotal role in the pathogenesis of angiogenesis.
Izuta
Hiroshi
H
Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, Mitahora-higashi, Japan.
Chikaraishi
Yuichi
Y
Adachi
Tetsuo
T
Shimazawa
Masamitsu
M
Sugiyama
Tetsuya
T
Ikeda
Tsunehiko
T
Hara
Hideaki
H
D002465:Cell Movement; D049109:Cell Proliferation; D003930:Diabetic Retinopathy / Q000097:blood* / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D042783:Endothelial Cells / Q000201:enzymology / Q000473:pathology; D005110:Extracellular Space / Q000201:enzymology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000150:complications / Q000201:enzymology; D012167:Retinal Perforations / Q000097:blood / Q000150:complications / Q000201:enzymology / Q000473:pathology; D013482:Superoxide Dismutase / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D014822:Vitreous Body / Q000378:metabolism* / Q000473:pathology*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013482:Superoxide Dismutase