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.
Highlights
The Wnt/β-catenin signaling pathway is a multifunctional pathway that is involved in embryonic development and controls homeostatic self-renewal in various adult tissues[5]
Our recent study found that changes of DKK-1 levels in the circulation are associated with the development of diabetic retinopathy[12], in which over-activation of the Wnt pathway plays a pathogenic role
Our results showed that decreased circulating levels of DKK-1 are associated with exudative age-related macular degeneration (AMD), but not with atrophic AMD, and the degrees of the DKK-1 decrease are associated with the progression or severity of choroidal neovascularization (CNV) in exudative AMD; the lower DKK-1 levels in the circulation are associated with the higher likelihood of having exudative AMD
Summary
The Wnt/β-catenin signaling pathway is a multifunctional pathway that is involved in embryonic development and controls homeostatic self-renewal in various adult tissues[5]. Our recent study found that changes of DKK-1 levels in the circulation are associated with the development of diabetic retinopathy[12], in which over-activation of the Wnt pathway plays a pathogenic role. Our previous studies, based on cell culture and the laser-induced CNV animal model, demonstrated that the Wnt/β-catenin signaling pathway plays an important role in the development of CNV. In order to better understand the role of the Wnt pathway in the pathogenesis of AMD and identify a biomarker for this disease, we measured plasma DKK-1 levels in exudative AMD patients and investigated if circulating DKK-1 levels are associated with this disease in the present study. We determined the correlation of DKK-1 levels with clinical profiles, such as subtype of CNV, severity of the disease, and analyzed the potential value of circulating DKK-1 levels as a biomarker for exudative AMD
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