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)-1alpha, MIP-1beta, 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-1alpha, MIP-1beta, 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-1beta, RANTES, and VEGF mean serum levels were significantly raised in diabetic probands while IP-10, MCP-1, and MIP-1alpha 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-1beta (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-1beta, RANTES, and VEGF in the serum. These findings support the concept of an angiogenic and inflammatory element in the development of diabetic retinopathy.