Multiplex bead analysis of vitreous and serum concentrations of inflammatory and proangiogenic factors in diabetic patients

PURPOSE: To investigate the role of inflammatory and angiogenic factors in the pathogenesis of diabetic retinopathy, we determined, in diabetic patients and controls, vitreous and serum concentrations of interferon-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, MIP-1β, regulated upon activation, normal T-expressed and secreted (RANTES), and vascular endothelial growth factor (VEGF). METHODS: We recruited 36 probands with type 2 diabetes mellitus (15 noninsulin-dependent and 21 insulin-dependent) and 69 normal controls. Using Cytometric Bead Array Technology, we measured vitreous and serum concentrations of IP-10, MCP-1, MIP-1α, MIP-1β, RANTES, and VEGF. RESULTS: In diabetic patients the mean vitreous levels of IP-10, MCP-1 and VEGF were significantly higher compared normal controls. [IP-10 (pg/mL) 254.84 +/−311.67 versus 78.90 +/− 67.94 (p<0.001); MCP-1 (pg/mL) 1127.14 +/− 738.91 versus 700.80 +/−419.21 (p=0.002); VEGF (pg/mL) 954.98 +/− 2315.09 versus 37.90 +/− 28.51(p<0.001)]. Vitreous levels of VEGF correlated with vitreous levels of both IP-10 and MCP-1 (p<0.05). MIP-1β, RANTES, and VEGF mean serum levels were significantly raised in diabetic probands while IP-10, MCP-1, and MIP-1α serum levels showed no significant elevation compared to controls [IP-10 (pg/mL) 346.20 +/− 287.36 versus 328.74 +/−352.35 (p=0.88); MCP-1(pg/mL) 133.10 +/− 89.10 versus 141.47 +/− 222.15 (p=0.50); MIP-1β (pg/mL) 184.40 +/− 100.20 versus 139.56 +/− 151.38 (p=0.003); RANTES (pg/mL) 51336.23 +/− 19940.31 versus 33629.2 +/− 33301.0 (p=0.002); VEGF (pg/mL) 304.88 +/− 257.52 versus 154.45 +/− 114.78 (p<0.001)]. CONCLUSIONS: Our results suggest that in diabetics, there is an upregulation of IP-10, MCP-1, and VEGF in the vitreous and an upregulation of MIP-1β, RANTES, and VEGF in the serum. These findings support the concept of an angiogenic and inflammatory element in the development of diabetic retinopathy.