Expression of high-mobility groups box-1/receptor for advanced glycation end products/osteopontin/early growth response-1 pathway in proliferative vitreoretinal epiretinal membranes

PURPOSE The high-mobility group box -1 (HMGB1)/receptor for advanced glycation end products (RAGE)/osteopontin (OPN)/early growth response-1 (Egr-1) pathway is involved in inflammation, angiogenesis, and fibrosis. We investigated the expression of the components of this pathway in proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR) epiretinal membranes. METHODS Nine active and 13 inactive membranes from patients with PDR and 21 membranes from patients with PVR were studied by immunohistochemistry. RESULTS In PDR membranes, vascular endothelial cells expressed HMGB1, RAGE, OPN, and Egr-1 in 21, 15, 20, and 16 membranes, respectively. Stromal cells expressed HMGB1, RAGE, OPN, and Egr-1 in 21, 20, 20, and 16 membranes, respectively. Significant correlations were detected between the number of blood vessels expressing the panendothelial cell marker CD34 and the number of blood vessels and stromal cells expressing HMGB1, RAGE, and OPN. The numbers of blood vessels and stromal cells expressing CD34, HMGB1, RAGE, and OPN and stromal cells expressing Egr-1 were significantly higher in active membranes than in inactive membranes. In PVR membranes, spindle-shaped myofibroblasts expressing α-smooth muscle actin coexpressed HMGB1, RAGE, OPN, and Egr-1. CONCLUSIONS The HMGB1/RAGE/OPN/Egr-1 pathway may be involved in inflammatory, angiogenic and fibrotic responses in proliferative vitreoretinal disorders.