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Purpose: We investigated the expression of the proinflammatory and proangiogenic factor osteoprotegerin (OPG) and its ligands, receptor activator of nuclear factor-κB ligand (RANKL), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and the receptor RANK in proliferative diabetic retinopathy (PDR).Materials and Methods: Vitreous samples from PDR and nondiabetic control patients and epiretinal membranes from PDR patients were studied by enzyme-linked immunosorbent assay, immunohistochemistry, and Western blot analysis.Results: Vascular endothelial growth factor, OPG, and soluble RANK levels in vitreous samples from PDR patients were significantly higher than that in nondiabetic controls. Soluble TRAIL levels were significantly lower in PDR patients than that in nondiabetic control, whereas soluble RANKL levels did not differ significantly. RANKL, RANK, and TRAIL were expressed in vascular endothelial cells, myofibroblasts, and CD45-expressing leukocytes in PDR epiretinal membranes.Conclusions: Dysregulated expression of OPG/RANKL/RANK pathway and TRAIL might be related to inflammation and angiogenesis in PDR. [ABSTRACT FROM AUTHOR]

Purpose: 150‐kDa oxygen‐regulated protein (ORP150), a member of heat‐shock protein family located in endoplasmic reticulum (ER), has a critical role in secretion of vascular endothelial growth factor (VEGF). We investigated expression levels of ORP150 and correlated these levels with VEGF and total vitreous antioxidant capacity (TAC) in proliferative diabetic retinopathy (PDR). We also examined expression of ORP150 in retinas of diabetic rats and in human retinal microvascular endothelial cells (HRMEC). Methods: Vitreous samples from 40 PDR and 20 non‐diabetic patients, epiretinal membranes from 14 patients with PDR, retinas of rats and HRMEC were studied by enzyme‐linked immunosorbent assay, immunohistochemistry and Western blot analysis. Results: We showed a significant increase in expression of VEGF and ORP150 in vitreous samples from PDR patients compared with controls (p < 0.0001 for both comparisons). Total vitreous antioxidant capacity (TAC) levels were significantly lower in patients with PDR than those in controls (p < 0.0001). Vascular endothelial growth factor (VEGF) and ORP150 levels in PDR with active neovascularization were significantly higher than that in inactive PDR (p = 0.016; p = 0.011, respectively). A significant positive correlation was observed between levels of ORP150 and levels of VEGF (r = 0.42; p = 0.001). In epiretinal membranes, ORP150 was expressed in vascular endothelial cells and stromal cells. We also demonstrated colocalization of the nuclear cell proliferation marker Ki67 and ORP150 in endothelial cells of pathologic new blood vessels. 150‐kDa oxygen‐regulated protein (ORP150) levels were significantly increased in rat retinas after induction of diabetes. Vascular endothelial growth factor (VEGF) and the pro‐inflammatory cytokines interleukin‐6 (IL‐6) and tumour necrosis factor‐α (TNF‐α) induced upregulation of ORP150 in HRMEC. Conclusion: These results suggest a role for ORP150 in PDR angiogenesis. [ABSTRACT FROM AUTHOR]