PurposeTo measure levels of high-mobility group box −1 (HMGB1) and soluble receptor for advanced glycation end products (sRAGE) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and to correlate their levels with clinical disease activity and the levels of the inflammatory biomarkers monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-1β (IL-1β), and granulocyte macrophage colony-stimulating factor (GM-CSF). In addition, we examined the expression of HMGB1 in the retinas of diabetic mice.MethodsVitreous samples from 29 PDR and 17 nondiabetic patients were studied by enzyme-linked immunosorbent assay. Retinas of mice were examined by immunofluorescence analysis and western blotting.ResultsHMGB1 was detected in all vitreous samples and sRAGE was detected in 5 PDR samples. IL-1β was detected in 3PDR samples and GM-CSF was not detected. Mean HMGB1 levels in PDR with active neovascularization were twofold and threefold higher than that in inactive PDR and nondiabetic patients, respectively. Mean HMGB1 levels in PDR patients with hemorrhage were significantly higher than those in PDR patients without hemorrhage and nondiabetic patients (p=0.0111). There were significant correlations between levels of HMGB1 and levels of MCP-1 (r=0.333, p=0.025) and sICAM-1 (r=0.548, p<0.001). HMGB1 expression was also upregulated in the retinas of diabetic mice.ConclusionsSubclinical chronic inflammation might contribute to the progression of PDR.

Purpose To measure the levels of LPA and LPA‐producing enzymes, autotaxin (ATX) and acylglycerol kinase (AGK) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and to correlate their levels with clinical disease activity and the level of vascular endothelial growth factor (VEGF). In addition, we examined the expression of ATX, AGK and VEGFR‐2 in the retinas of diabetic rats. Methods Vitreous samples from 42 PDR and 35 nondiabetic patients were studied by enzyme‐linked immunosorbent assay. Vitreous samples and retinas of rats were examined by Western blot analysis. Results VEGF, LPA and AGK levels in vitreous samples from PDR patients were significantly higher than those in control patients without diabetes (p<0.001 for all comparisons). ATX levels in PDR with active neovascularization and inactive PDR were significantly lower than those in nondiabetic patients (p=0.045). Mean VEGF and AGK levels in PDR with active neovascularization were significantly higher than those in inactive PDR and nondiabetic patients (p<0.001 for both comparisons). A significant correlation was observed between levels of VEGF and levels of AGK in PDR patients (r=0.954, p<0.001). Western blot analysis revealed a significant increase in the expression of AGK and VEGFR‐2 in vitreous samples and the retinas of diabetic rats compared to nondiabetic controls, whereas ATX was significantly downregulated. Conclusion ATX‐AGK‐LPA signaling axis might be an important player in the development and progression of diabetic retinopathy.