title: Intraocular activation of angiogenic and inflammatory pathways in uveal melanoma.
abstract: OBJECTIVE
  To identify and quantify angiogenic and inflammatory cytokines in aqueous and vitreous humor in eyes with untreated uveal melanoma and to analyze clinicopathologic correlations.
  
  
  METHODS
  Intraocular fluid samples of patients (uveal melanoma aqueous n = 21, vitreous n = 34) and controls (cataract aqueous n = 41, vitreomacular traction aqueous n = 35, vitreous n = 36) were taken intraoperatively and analyzed using Luminex xMAP suspension array technology. Beadlyte kits were used for detection of 28 different cytokines.
  
  
  RESULTS
  Flt-3 ligand, interleukin (IL) 1α, IL-6, IL-8, interferon-γ inducible protein (IP)-10, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1α, platelet-derived growth factor AA, and vascular endothelial growth factor were significantly elevated in aqueous and vitreous of melanoma eyes when compared with controls. Eotaxin was significantly elevated in aqueous, and IL-7 and RANTES were significantly elevated in vitreous samples of melanoma eyes. Interferon-γ inducible protein 10, macrophage inflammatory protein 1α (aqueous and vitreous), Flt-3 ligand, IL-6, IL-8, and MCP-1 (vitreous) correlated with tumor dimensions. Further correlations were found between infiltration of Bruch membrane and Flt-3 ligand, MCP-1 (aqueous and vitreous), IL-8, interferon-γ inducible protein 10, macrophage inflammatory protein 1α, and platelet-derived growth factor AA (vitreous). Analyzing 16 paired aqueous and vitreous melanoma samples, Flt-3 ligand, IL-7, interferon-γ inducible protein 10, MCP-1, and platelet-derived growth factor AA were significantly elevated in vitreous, and IL-1α and vascular endothelial growth factor in aqueous samples.
  
  
  CONCLUSIONS
  A range of significantly elevated angiogenic, inflammatory, and chemotactic cytokines in eyes with uveal melanoma supports the link between inflammation and tumorigenesis.
authors.affiliation: Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.
authors.forename: Roman
authors.initials: R
authors.lastname: Dunavoelgyi
authors.forename: Marion
authors.initials: M
authors.lastname: Funk
authors.forename: Stefan
authors.initials: S
authors.lastname: Sacu
authors.forename: Michael
authors.initials: M
authors.lastname: Georgopoulos
authors.forename: Gerhard
authors.initials: G
authors.lastname: Zlabinger
authors.forename: Martin
authors.initials: M
authors.lastname: Zehetmayer
authors.forename: Ursula
authors.initials: U
authors.lastname: Schmidt-Erfurth
mesh_terms: D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D001082:Aqueous Humor / Q000378:metabolism*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D016207:Cytokines / Q000378:metabolism*; D015353:Eye Enucleation; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D009006:Monosomy / Q000235:genetics; D011446:Prospective Studies; D014604:Uveal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D014822:Vitreous Body / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D016207:Cytokines