title: Profile of lipid and protein autacoids in diabetic vitreous correlates with the progression of diabetic retinopathy.
abstract: OBJECTIVE
  This study was aimed at obtaining a profile of lipids and proteins with a paracrine function in normal and diabetic vitreous and exploring whether the profile correlates with retinal pathology.
  
  
  METHODS
  Vitreous was recovered from 47 individuals undergoing vitreoretinal surgery: 16 had nonproliferative diabetic retinopathy (NPDR), 15 had proliferative diabetic retinopathy, 7 had retinal detachments, and 9 had epiretinal membranes. Protein and lipid autacoid profiles were determined by protein arrays and mass spectrometry-based lipidomics.
  
  
  RESULTS
  Vitreous lipids included lipoxygenase (LO)- and cytochrome P450 epoxygenase (CYP)-derived eicosanoids. The most prominent LO-derived eicosanoid was 5-hydroxyeicosate traenoic acid (HETE), which demonstrated a diabetes-specific increase (P = 0.027) with the highest increase in NPDR vitreous. Vitreous also contained CYP-derived epoxyeicosatrienoic acids; their levels were higher in nondiabetic than diabetic vitreous (P < 0.05). Among inflammatory, angiogenic, and angiostatic cytokines and chemokines, only vascular endothelial growth factor (VEGF) showed a significant diabetes-specific profile (P < 0.05), although a similar trend was noted for tumor necrosis factor (TNF)-alpha. Soluble VEGF receptors R1 and R2 were detected in all samples with lowest VEGF-R2 levels (P < 0.05) and higher ratio of VEGF to its receptors in NPDR and PDR vitreous.
  
  
  CONCLUSIONS
  This study is the first to demonstrate diabetes-specific changes in vitreous lipid autacoids including arachidonate and docosahexanoate-derived metabolites indicating an increase in inflammatory versus anti-inflammatory lipid mediators that correlated with increased levels of inflammatory and angiogenic proteins, further supporting the notion that inflammation plays a role the pathogenesis of this disease.
authors.affiliation: Department of Pharmacology, New York Medical College, Valhalla, New York, USA. michal_schwartzman@nymc.edu
authors.forename: Michal Laniado
authors.initials: ML
authors.lastname: Schwartzman
authors.forename: Pavel
authors.initials: P
authors.lastname: Iserovich
authors.forename: Katherine
authors.initials: K
authors.lastname: Gotlinger
authors.forename: Lars
authors.initials: L
authors.lastname: Bellner
authors.forename: Michael W
authors.initials: MW
authors.lastname: Dunn
authors.forename: Mauro
authors.initials: M
authors.lastname: Sartore
authors.forename: Maria
authors.initials: M
authors.lastname: Grazia Pertile
authors.forename: Andrea
authors.initials: A
authors.lastname: Leonardi
authors.forename: Sonal
authors.initials: S
authors.lastname: Sathe
authors.forename: Ann
authors.initials: A
authors.lastname: Beaton
authors.forename: Lynn
authors.initials: L
authors.lastname: Trieu
authors.forename: Robert
authors.initials: R
authors.lastname: Sack
mesh_terms: D000368:Aged; D012898:Autacoids / Q000032:analysis* / Q000378:metabolism; D018925:Chemokines / Q000032:analysis* / Q000378:metabolism; D016207:Cytokines / Q000032:analysis* / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000378:metabolism*; D018450:Disease Progression; D015777:Eicosanoids / Q000032:analysis* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D014822:Vitreous Body / Q000737:chemistry* / Q000378:metabolism
chemical_list: D012898:Autacoids; D018925:Chemokines; D016207:Cytokines; D015777:Eicosanoids