Decreased Circulating Levels of Dickkopf-1 in Patients with Exudative Age-related Macular Degeneration

Abstract

Aberrant activation of the Wnt/β-catenin signaling pathway plays a pathogenic role in retinal inflammation and neovascularization. Here, we investigated whether circulating levels of Dickkopf-1 (DKK-1), a specific inhibitor of this pathway, are altered in patients with exudative age-related macular degeneration (AMD). Plasma was obtained from 128 patients with exudative AMD, 46 patients with atrophic AMD and 111 healthy controls. DKK-1 levels in plasma were measured using ELISA, and data analyzed with one-way ANOVA, logistic regression analysis and receiver-operating characteristic analysis (ROC). We found that DKK-1 levels were decreased in exudative AMD patients, compared with healthy controls (P < 0.001) and atrophic AMD patients (P < 0.001). The decrease was more prominent in patients with classic choroidal neovascularization (CNV) than those with occult CNV (P < 0.001). The odds ratio (OR) of exudative AMD was 11.71 (95% CI; 5.24-6.13) for lowest versus upper quartile of DKK-1 levels. For discriminating exudative AMD patients, the optimum diagnostic cutoff of DKK-1 was 583.1 pg/mL with the area under curve (AUC) 0.76 (95% CI, 0.70-0.82; P < 0.001), sensitivity 78.1% and specificity 63.1%. These findings suggested that decreased circulating DKK-1 levels are associated with the development and severity of exudative AMD, and have potential to become a biomarker for exudative AMD.