title: Dysregulated heme oxygenase-ferritin system in pterygium pathogenesis.
abstract: OBJECTIVE
  Cyclooxygenase (COX)-, lipoxygenase (LOX)-, and cytochrome P450 monooxygenase (CYP)-derived eicosanoids have been implicated in ocular surface inflammation and neovascularization. These eicosanoids are subjected to regulation by enzymes, such as heme oxygenases (HOs) and ferritin.
  
  
  METHODS
  Quantitative polymerase chain reaction and lipidomics based on liquid chromatography-tandem mass spectrometry were performed on pterygia from patients undergoing surgical pterygium excision. Control tissues consisted of donor corneas. In addition, lipidomics based on liquid chromatography-tandem mass spectrometry was performed on tears collected from patients before the surgery.
  
  
  RESULTS
  Messenger RNA (mRNA) expression of HO-2, the constitutive HO isoform, was upregulated by 40% in pterygia compared with control tissue, whereas the mRNA level of the inducible form, HO-1, was downregulated by more than 50%. Levels of CYP4B1 mRNA showed an approximate 2-fold increase in pterygia compared with control. Lipidomic analysis of tissues indicated a moderate elevation in Prostaglandin E2 and thromboxane B2 levels in pterygia compared with control. Among the LOX-derived metabolites, the antiinflammatory-hydroxyeicosatetraenoic acid (15-HETE) levels were significantly reduced in pterygia (79.3 ± 48.11 pg/mg protein) compared with control (586.2 ± 213.5 pg/mg protein), whereas the proinflammatory LOX- and CYP4B1-derived 12-HETE levels were 10-fold higher in pterygia (2768 ± 832.3 pg/mg protein) compared with control (231.4 ± 87.35 pg/mg protein). Prostaglandin E2 and HETEs were also present in tears from patients with pterygium but were not detected in tears from healthy volunteers. The mRNA expression levels of both light and heavy chain ferritin were 60% and 30% lower, respectively, in pterygia compared with control.
  
  
  CONCLUSIONS
  We believe that a dysfunctional HO-ferritin system leads to increased levels of proinflammatory mediators, thus contributing to the inflammation characteristic of pterygia.
authors.affiliation: Department of Pharmacology, New York Medical College, Valhalla, NY, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Fox
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Gotlinger
authors.forename: Michael W
authors.initials: MW
authors.lastname: Dunn
authors.forename: Olivia L
authors.initials: OL
authors.lastname: Lee
authors.forename: Tatyana
authors.initials: T
authors.lastname: Milman
authors.forename: Gerald
authors.initials: G
authors.lastname: Zaidman
authors.forename: Michal L
authors.initials: ML
authors.lastname: Schwartzman
authors.forename: Lars
authors.initials: L
authors.lastname: Bellner
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000378:metabolism; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D005293:Ferritins / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D007527:Isoenzymes; D008297:Male; D008875:Middle Aged; D011625:Pterygium / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013666:Tears / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D007527:Isoenzymes; D012333:RNA, Messenger; D013929:Thromboxane B2; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D005293:Ferritins; D001189:Aryl Hydrocarbon Hydroxylases; C095029:cytochrome P-450 CYP4B1; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; D015232:Dinoprostone