Regulation of angiogenesis in diabetic retinopathy: possible balance between vascular endothelial growth factor and endostatin.
OBJECTIVE
To investigate the mechanisms of regulation between vascular endothelial growth factor (VEGF) as a stimulator and endostatin as an inhibitor of angiogenesis in diabetic retinopathy (DR).


METHODS
One hundred fifty-nine eyes of 120 diabetic patients were studied. Concentrations of VEGF and endostatin in vitreous fluid and aqueous humor, obtained from the eyes during ocular surgery, were measured by enzyme-linked immunosorbent assay. The severity of DR was quantified according to the Early Treatment Diabetic Retinopathy Study retinopathy severity scale; fundus findings, including soft exudates, intraretinal microvascular abnormalities, venous abnormalities, new vessels elsewhere, new vessels on the disc, vitreous hemorrhage, and retinal detachment, were graded and evaluated. Concentrations of VEGF and endostatin in plasma were also measured by enzyme-linked immunosorbent assay.


METHODS
Concentrations of VEGF and endostatin in vitreous fluid and plasma. The correlations among the clinical records and the levels of VEGF and endostatin were analyzed statistically.


RESULTS
The concentrations of VEGF in aqueous humor and vitreous fluid were significantly correlated with the severity of DR (rho = 0.447, P<.001 and rho = 0.363, P =.007, respectively). The concentrations of endostatin in aqueous humor and vitreous fluid were also significantly correlated with the severity of DR (rho = 0.302, P<.001 and rho = 0.344, P =.009, respectively). The slope of the regression line between the VEGF and endostatin concentrations in vitreous fluid differed significantly between active DR and quiescent DR (P =.04). The concentrations of VEGF and endostatin in the eyes were not correlated with those in the plasma.


CONCLUSIONS
These results show that both VEGF and endostatin are correlated with angiogenesis in DR. Our study suggests that the regulation mechanism between VEGF and endostatin is associated with the activity of DR and may be a good candidate to develop useful therapeutic agents for proliferative DR.
Noma
Hidetaka
H
Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University, Kawada-cho, Shinuku-ku, Japan.
Funatsu
Hideharu
H
Yamashita
Hidetoshi
H
Kitano
Shigehiko
S
Mishima
Hiromu K
HK
Hori
Sadao
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D001082:Aqueous Humor / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology; D043169:Endostatins; D016228:Endothelial Growth Factors / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism*; D015861:Retinal Neovascularization / Q000378:metabolism* / Q000473:pathology; D012171:Retinal Vessels / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014822:Vitreous Body / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D043169:Endostatins; D016228:Endothelial Growth Factors; D008222:Lymphokines; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D003094:Collagen