Plasma and vitreous fluid levels of Dickkopf-1 in patients with diabetic retinopathy

Abstract

Purpose Dickkopf-1 (DKK-1) is a secreted inhibitor of the Wnt/b-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 nondiabetic patients. DKK-1 concentrations in samples were determined using enzymelinked immunosorbent assay. Variables were compared with the Kruskal-Wallis H test, Mann-Whitney U-test, and w 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; Po0.001) and NDR patients (693.04 pg/ml, 305.43-1218.35; Po0.001). 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 ¼ 0.003). Vitreous absolute DKK-1 levels in PDR patients (259.04 pg/ml, 104.44-596.96) were higher than in nondiabetic controls (138.26 pg/ml, 18.69-239.52; Po0.001). 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 (Po0.001 for controls; P ¼ 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.

Oxidative stress and diabetic retinopathy: development and treatment

“…Table 3 summarizes the treatment options for clinical management of DR complications. [46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64] Table 4 also depicts the data of a study in an animal model where some pertinent particles believed to improve oxidative stress as well as prevent or delay DR development. [65][66][67][68][69][70][71][72][73][74][75] It is a proven fact that oxidative stress enhances the progression of DR hence, decreasing the degree of such stress has been observed in clinical situations to contra arrest DR pathological problems.…”

DKK1 inhibits proliferation and migration in human retinal pigment epithelial cells via the Wnt/β-catenin signaling pathway

“…It has been reported that the protein expression level of DKK1 is significantly increased in the serum of patients with rheumatoid arthritis (6), and DKK1 regulates bone development and accrual and maintenance of bone mass (7,8). Recently, a study showed that plasma DKK-1 levels were significantly lower in DR patients compared with non-diabetic controls and non-DR (NDR) patients (9). Furthermore, DKK-1 levels were lower in proliferative DR (PDR) patients compared with non-proliferative PDR (NPDR) patients (9).…”

“…Recently, a study showed that plasma DKK-1 levels were significantly lower in DR patients compared with non-diabetic controls and non-DR (NDR) patients (9). Furthermore, DKK-1 levels were lower in proliferative DR (PDR) patients compared with non-proliferative PDR (NPDR) patients (9). However, there is no information regarding the effects of DKK1 in RPE cells.…”

A Prospective Assessment of Periprosthetic Bone Mineral Density and Osteoimmunological Biomarkers Variations After Total Knee Replacement Surgery

“…The levels of DKK-1 and of the bone-protective marker OPG protein level were comparable to the reference range (18,19) at T0 and, showed non-significant oscillations in the subsequent follow-up points. A specular pattern of was observed between the oscillating expression of these two biomarkers at all time points.…”