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

Mol Vis. 2008 Mar 27:14:637-43.

Abstract

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.

MeSH terms

  • Aged
  • Angiogenesis Inducing Agents / blood
  • Angiogenesis Inducing Agents / metabolism*
  • Chemokine CCL2 / metabolism
  • Chemokine CCL4 / blood
  • Chemokine CCL5 / blood
  • Chemokine CXCL10 / metabolism
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / metabolism*
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Humans
  • Inflammation Mediators / blood
  • Inflammation Mediators / metabolism*
  • Male
  • Middle Aged
  • Osmolar Concentration
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor A / metabolism
  • Vitreous Body / metabolism*

Substances

  • Angiogenesis Inducing Agents
  • CCL2 protein, human
  • CXCL10 protein, human
  • Chemokine CCL2
  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokine CXCL10
  • Inflammation Mediators
  • Vascular Endothelial Growth Factor A