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(Investigative Ophthalmology and Visual Science. 2005;46:4295-4301.)
© 2005 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.04-1057
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Serum Inflammatory Markers in Diabetic Retinopathy

Annal D. Meleth,1,2 Elvira Agrón,2 Chi-Chao Chan,3 George F. Reed,2 Kiran Arora,2 Gordon Byrnes,4 Karl G. Csaky,5 Frederick L. Ferris, III,2 and Emily Y. Chew2

1From the Howard Hughes Medical Institute, the 2Division of Epidemiology and Clinical Research, the 3Laboratory of Immunology, and the 5Office of the Scientific Director, National Eye Institute, National Institutes of Health, Bethesda, Maryland; and the 4Retina Group of Washington, Rockville, Maryland.

PURPOSE. To evaluate the association of serum factors with the severity of diabetic retinopathy and to assess their presence in retinal tissue obtained at autopsy.

METHODS. The following serum factors of 93 subjects were examined at the National Eye Institute (NEI) clinical center: the chemokines regulated on activation, normal T-cell expressed and presumably secreted (RANTES)/CCL5, epithelial neutrophil activator (ENA)-78/CXCL5, interferon-induced protein (IP)-10/CXCL10, stromal cell–derived factor (SDF)-1{alpha}/CXCLl2, monocyte chemoattractant protein (MCP)-1/CCL2, macrophage inflammatory protein (MIP)-1{alpha}/CCL3, interleukin (IL)-8/CXCL8; the cytokine IL-6; the cell adhesion molecules intercellular adhesion molecule (ICAM-1/CD54) and vascular cell adhesion molecule (VCAM/CD106); and the growth factor vascular endothelial growth factor (VEGF). Logistic regression was performed to assess the association of these factors with age, sex, severity of retinopathy, hemoglobin A1C, total cholesterol, creatinine, duration of diabetes, and presence of macular edema. The outcome assessed was severity of retinopathy. Frozen sections of two donor eyes obtained at autopsy from a donor with documented severe nonproliferative diabetic retinopathy and diabetic macular edema and of a normal nondiabetic eye were processed by immunoperoxidase staining with primary antibodies against RANTES, MCP-1, ICAM-1, and LFA-1{alpha}/CD11a.

RESULTS. The levels of RANTES and SDF-1{alpha} were significantly elevated in patients with at least severe nonproliferative diabetic retinopathy compared with those with less severe diabetic retinopathy (P < 0.001 and 0.007, respectively). Positive immunostaining was observed in the inner retina for MCP-1 and RANTES of the patient with diabetes. Staining was strongly positive throughout the diabetic retina for ICAM-1. Normal retinal tissues showed little reactivity.

CONCLUSIONS. Serum chemokines were significantly elevated in patients with at least severe nonproliferative diabetic retinopathy compared with those who had less severe retinopathy. Elevated levels of the chemokines and cell adhesion molecules were also identified in eyes of a donor with ischemic diabetic retinopathy. These findings provide evidence to support the role of inflammation in the pathogenesis of diabetic retinopathy.




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