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Regulation of Angiogenesis in Diabetic Retinopathy
Possible Balance Between Vascular Endothelial Growth Factor and Endostatin
Hidetaka Noma, MD;
Hideharu Funatsu, MD;
Hidetoshi Yamashita, MD;
Shigehiko Kitano, MD;
Hiromu K. Mishima, MD;
Sadao Hori, MD
Arch Ophthalmol. 2002;120:1075-1080.
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.
Main Outcome Measures 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 ( = 0.447, P<.001 and = 0.363, P = .007, respectively).
The concentrations of endostatin in aqueous humor and vitreous fluid were
also significantly correlated with the severity of DR ( = 0.302, P<.001 and = 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.
From the Departments of Ophthalmology, Diabetes Center, Tokyo Women's
Medical University, Tokyo (Drs Noma, Funatsu, and Kitano), Hiroshima University
Medical School, Hiroshima (Drs Noma and Mishima), and Yamagata University
Medical School, Yamagata (Dr Yamashita), and Tokyo Women's Medical University
(Dr Hori), Japan.
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