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Fangfang Qiu, Jia He, Yueping Zhou, Zhen Liu, Jian-Xing Ma, Zuguo Liu; Plasma and vitreous fluid levels of Dickkopf-1 in patients with diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2446.
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© ARVO (1962-2015); The Authors (2016-present)
Dickkopf-1 (DKK-1) is a secreted inhibitor of the Wnt/β-catenin signaling pathway which is activated in the retina of diabetic retinopathy (DR) patients. We investigated whether plasma and vitreous DKK-1 levels are associated with DR in type 2 diabetic patients.
Plasma samples were collected from 86 type 2 diabetic patients including 66 DR (29 non-proliferative DR [NPDR] and 37 proliferative DR [PDR]) and 20 non-DR patients (NDR), and 100 non-diabetes controls. Vitreous samples were obtained from 15 PDR and 12 non-diabetic patients. DKK-1 concentrations in samples were determined by ELISA.
Plasma DKK-1 levels were significantly lower in DR patients (median: 530.91 pg/ml, range: 137.11-1190.31) than those in non-diabetes controls (656.83 pg/ml, 171.63-1795.08; P<0.0001) and NDR patients (654.15 pg/ml, 305.43-1218.35; P=0.013); they were lower in PDR patients (478.86 pg/ml, 137.10-1077.32) compared to NPDR patients (594.86 pg/ml, 256.36-1393.27; P=0.038). Vitreous absolute DKK-1 levels in PDR patients (243.73 pg/ml, 104.44-596.96) were higher than those in non-diabetic controls (144.99 pg/ml, 18.69-239.52) and were identical between the both groups after normalizing by total vitreous protein concentrations. DKK-1 levels in vitreous were lower than those in plasma in both groups (both P<0.001).
Decreased circulating DKK-1 levels are associated with the presence and progression of DR. The decreased DKK-1 levels may contribute to the Wnt pathway activation and have potential to become a biomarker for prediction of DR. Vitreous DKK-1 in PDR patients is increased due to the breakdown of blood-retinal barrier, but they are at very low levels.
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