The aim of this study was to measure the levels of high-mobility group box-1 (HMGB1) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and to correlate its levels with clinical disease activity and the levels of vascular endothelial growth factor (VEGF), the angiogenic cytokine granulocyte-colony-stimulating factor (G-CSF), the endothelial cell angiogenic markers soluble vascular endothelial-cadherin (sVE-cadherin), and soluble endoglin (sEng). Vitreous samples from 36 PDR and 21 nondiabetic patients were studied by enzyme-linked immunosorbent assay. HMGB1, VEGF, sVE-cadherin, and sEng levels were significantly higher in PDR patients than in nondiabetics ( ; <0.001; <0.001; 0.003, resp.). G-CSF was detected in only 3 PDR samples. In the whole study group, there was significant positive correlation between the levels of HMGB1, and sVE-cadherin ( , ). In PDR patients, there was significant negative correlation between the levels of sVE-cadherin and sEng ( , ). Exploratory regression analysis identified significant associations between active PDR and high levels of VEGF (odds ratio = 76.4; 95% confidence interval = 6.32–923) and high levels of sEng (odds ratio = 6.01; 95% confidence interval？= 1.25–29.0). Our findings suggest that HMGB1, VEGF, sVE-cadherin and sEng regulate the angiogenesis in PDR. 1. Introduction Ischemia-induced angiogenesis and expansion of extracellular matrix in association with the outgrowth of fibrovascular membranes at the vitreoretinal interface is the pathological hallmark in proliferative diabetic retinopathy (PDR). Vascular endothelial growth factor (VEGF), an endothelial cell mitogen that also enhances vascular permeability, is thought to be the major angiogenesis factor in PDR [1]. In addition, strong evidence indicates that chronic low-grade inflammation is implicated in the pathogenesis of diabetic retinopathy [2, 3]. Sustained proinflammatory responses in diabetic retinopathy are often associated with angiogenesis [2–5]. The causal relationship between inflammation and angiogenesis is now widely accepted [6]. An emerging issue in diabetic retinopathy research is the focus on the mechanistic link between chronic, low-grade inflammation and angiogenesis. High-mobility group box-1 protein (HMGB1) was initially discovered as a nuclear chromatin-binding protein that stabilizes nucleosome formation and facilitates transcription. Necrotic cell death can result in passive leakage of HMGB1 from the cell as the protein is then no longer bound to DNA. In addition, HMGB1 can be actively secreted by
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