title: Identification of VEGF-independent cytokines in proliferative diabetic retinopathy vitreous.
abstract: OBJECTIVE
  To identify inflammatory cytokines significantly elevated and independent of VEGF levels in the vitreous of proliferative diabetic retinopathy (PDR) patients that may serve as novel diagnostic factors or therapeutic targets.
  
  
  METHODS
  Thirty-nine cytokines and chemokines were measured from the vitreous of 72 patients undergoing vitrectomy (29 controls and 43 PDR) via a magnetic bead-based immunoassay. Patient information, including sex, age, history of smoking, cancer diagnosis and treatment, and presence of diabetes and hypertension were also collected. Univariate and multivariate logistic regression analyses were performed to assess the association of cytokine concentrations and patient demographics with disease.
  
  
  RESULTS
  Nineteen cytokines were significantly elevated in the vitreous of PDR patients compared with controls, including five novel cytokines that have not previously been associated with PDR: sCD40L, GM-CSF, IFNα2, IL-12p40, and MCP-3. Sixteen cytokines were found to be statistically independent of VEGF. Of these, 14 show a statistically significant interaction with VEGF, while two do not. With regards to patient demographics, age and hypertension were statistically significant risk factors with the odds of disease decreasing with increasing age and increasing 3-fold for hypertensive patients.
  
  
  CONCLUSIONS
  This is the first report of a comprehensive multiplex analysis to identify novel VEGF-independent cytokines associated with PDR. Of the 39 inflammatory cytokines tested, 16 are predictive of disease risk, independent of VEGF levels. These PDR-associated cytokines represent potential targets in the treatment of PDR, both in conjunction with anti-VEGF therapy, as well as for patients that are nonresponders to such therapy.
authors.affiliation: Laboratory of Cancer and Developmental Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Bromberg-White
authors.forename: Louis
authors.initials: L
authors.lastname: Glazer
authors.forename: Robert
authors.initials: R
authors.lastname: Downer
authors.forename: Kyle
authors.initials: K
authors.lastname: Furge
authors.forename: Elissa
authors.initials: E
authors.lastname: Boguslawski
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Duesbery
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000150:complications / Q000378:metabolism* / Q000601:surgery; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014821:Vitrectomy; D018630:Vitreoretinopathy, Proliferative / Q000209:etiology / Q000378:metabolism* / Q000601:surgery; D014822:Vitreous Body / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D042461:Vascular Endothelial Growth Factor A
keywords: VEGF; cytokine; diabetic retinopathy; vitreous