title: Serum inflammatory markers in diabetic retinopathy.
abstract: OBJECTIVE
  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)-1alpha/CXCLl2, monocyte chemoattractant protein (MCP)-1/CCL2, macrophage inflammatory protein (MIP)-1alpha/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 A(1C), 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-1alpha/CD11a.
  
  
  RESULTS
  The levels of RANTES and SDF-1alpha 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.
authors.affiliation: Howard Hughes Medical Institute, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Annal D
authors.initials: AD
authors.lastname: Meleth
authors.forename: Elvira
authors.initials: E
authors.lastname: Agrón
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
authors.forename: George F
authors.initials: GF
authors.lastname: Reed
authors.forename: Kiran
authors.initials: K
authors.lastname: Arora
authors.forename: Gordon
authors.initials: G
authors.lastname: Byrnes
authors.forename: Karl G
authors.initials: KG
authors.lastname: Csaky
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Ferris
authors.forename: Emily Y
authors.initials: EY
authors.lastname: Chew
mesh_terms: D015415:Biomarkers / Q000097:blood*; D015815:Cell Adhesion Molecules / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D003930:Diabetic Retinopathy / Q000097:blood*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D012173:Retinitis / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D016207:Cytokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A