F Qiu1, J He2, Y Zhou1, X Bai3, G Wu3, X Wang3, Z Liu1, Y Chen1, J-X Ma4, Z Liu1. 1. Eye Institute of Xiamen University, Xiamen, China. 2. 1] Eye Institute of Xiamen University, Xiamen, China [2] Eye Institute, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China. 3. Xiamen Eye Center Affiliated to Xiamen University, Xiamen, China. 4. Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Abstract
PURPOSE: Dickkopf-1 (DKK-1) is a secreted inhibitor of the Wnt/β-catenin signaling pathway, which plays a pathogenic role in diabetic retinopathy (DR). We aimed to investigate whether DKK-1 levels in the plasma and the vitreous are associated with DR in type 2 diabetes mellitus (DM) patients. METHODS: Case-control study: plasma samples were collected from 125 type 2 DM including 81 DR (29 non-proliferative DR (NPDR) and 52 proliferative DR (PDR)), 44 non-DR patients (NDR), and 100 non-diabetic controls. Undiluted vitreous fluid samples were obtained from 30 PDR and 25 non-diabetic patients. DKK-1 concentrations in samples were determined using enzyme-linked immunosorbent assay. Variables were compared with the Kruskal-Wallis H test, Mann-Whitney U-test, and χ(2)-test, when appropriate. RESULTS: Plasma DKK-1 levels were significantly lower in DR patients (median: 465.77 pg/ml, range: 137.11-1190.31) than in non-diabetic controls (656.83 pg/ml, 171.63-1795.08; P<0.001) and NDR patients (693.04 pg/ml, 305.43-1218.35; P<0.001). Furthermore, DKK-1 levels were lower in PDR patients (425.21 pg/ml, 137.10-1077.32) compared with NPDR patients (594.86 pg/ml, 256.36-1393.27; P=0.003). Vitreous absolute DKK-1 levels in PDR patients (259.04 pg/ml, 104.44-596.96) were higher than in non-diabetic controls (138.26 pg/ml, 18.69-239.52; P<0.001). After normalizing by total vitreous protein concentrations, however, there was no significant difference between the groups. DKK-1 levels in vitreous were lower than those in plasma in both groups (P<0.001 for controls; P=0.002 for PDR patients). CONCLUSIONS: Decreased plasma DKK-1 levels, which may contribute to the Wnt pathway activation, are associated with the presence and progression of DR, and have potential to become a biomarker for DR.
PURPOSE:Dickkopf-1 (DKK-1) is a secreted inhibitor of the Wnt/β-catenin signaling pathway, which plays a pathogenic role in diabetic retinopathy (DR). We aimed to investigate whether DKK-1 levels in the plasma and the vitreous are associated with DR in type 2 diabetes mellitus (DM) patients. METHODS: Case-control study: plasma samples were collected from 125 type 2 DM including 81 DR (29 non-proliferative DR (NPDR) and 52 proliferative DR (PDR)), 44 non-DR patients (NDR), and 100 non-diabetic controls. Undiluted vitreous fluid samples were obtained from 30 PDR and 25 non-diabeticpatients. DKK-1 concentrations in samples were determined using enzyme-linked immunosorbent assay. Variables were compared with the Kruskal-Wallis H test, Mann-Whitney U-test, and χ(2)-test, when appropriate. RESULTS: Plasma DKK-1 levels were significantly lower in DR patients (median: 465.77 pg/ml, range: 137.11-1190.31) than in non-diabetic controls (656.83 pg/ml, 171.63-1795.08; P<0.001) and NDR patients (693.04 pg/ml, 305.43-1218.35; P<0.001). Furthermore, DKK-1 levels were lower in PDR patients (425.21 pg/ml, 137.10-1077.32) compared with NPDR patients (594.86 pg/ml, 256.36-1393.27; P=0.003). Vitreous absolute DKK-1 levels in PDR patients (259.04 pg/ml, 104.44-596.96) were higher than in non-diabetic controls (138.26 pg/ml, 18.69-239.52; P<0.001). After normalizing by total vitreous protein concentrations, however, there was no significant difference between the groups. DKK-1 levels in vitreous were lower than those in plasma in both groups (P<0.001 for controls; P=0.002 for PDR patients). CONCLUSIONS: Decreased plasma DKK-1 levels, which may contribute to the Wnt pathway activation, are associated with the presence and progression of DR, and have potential to become a biomarker for DR.
Authors: R A Malik; C Li; W Aziz; J A Olson; A Vohra; K C McHardy; J V Forrester; A J M Boulton; P B Wilson; D Liu; D McLeod; S Kumar Journal: J Cell Mol Med Date: 2005 Jul-Sep Impact factor: 5.310
Authors: C P Wilkinson; Frederick L Ferris; Ronald E Klein; Paul P Lee; Carl David Agardh; Matthew Davis; Diana Dills; Anselm Kampik; R Pararajasegaram; Juan T Verdaguer Journal: Ophthalmology Date: 2003-09 Impact factor: 12.079
Authors: L P Aiello; R L Avery; P G Arrigg; B A Keyt; H D Jampel; S T Shah; L R Pasquale; H Thieme; M A Iwamoto; J E Park Journal: N Engl J Med Date: 1994-12-01 Impact factor: 91.245