Multiplex bead analysis of vitreous and serum concentrations of inflammatory and proangiogenic factors in diabetic patients.
OBJECTIVE
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.
Maier
Richard
R
Department of Ophthalmology, Medical University of Graz, Graz, Austria. richardmaier@chello.at
Weger
Martin
M
Haller-Schober
Eva-Maria
EM
El-Shabrawi
Yosuf
Y
Wedrich
Andreas
A
Theisl
Anna
A
Aigner
Reingard
R
Barth
Alfred
A
Haas
Anton
A
D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000097:blood / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000378:metabolism; D054407:Chemokine CCL4 / Q000097:blood; D018946:Chemokine CCL5 / Q000097:blood; D054357:Chemokine CXCL10 / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism; D014822:Vitreous Body / Q000378:metabolism*
D043925:Angiogenesis Inducing Agents; C111835:CCL2 protein, human; C114753:CXCL10 protein, human; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D018836:Inflammation Mediators; D042461:Vascular Endothelial Growth Factor A