title: Enzymes of urea synthesis are expressed at the ocular surface, and decreased urea in the tear fluid is associated with dry-eye syndrome.
abstract: OBJECTIVE
  The present study aims at determining whether enzymes of urea synthesis are expressed in the human lacrimal gland and in tissues of ocular surface (conjunctiva, cornea), to give evidence for the hypothesis that urea can be locally formed from ocular tissues and is important for the composition of the tear fluid.
  
  
  METHODS
  The presences of enzymes (arginase 1, 2 and agmatinase) that directly contribute to the formation of urea were investigated in the lacrimal gland and tissues of ocular surface by RT-PCR and immunohistochemistry. We collected tear fluid, aqueous humour, and blood samples from a total of 38 subjects, and tear fluid samples from a total of 78 subjects, with and without dry-eye syndrome (DES, keratoconjunctivitis sicca), and determined the urea concentration.
  
  
  RESULTS
  The enzymes arginase 1, 2 and agmatinase were expressed in all tissues examined except for arginase 1, which was not expressed in the cornea. There was no correlation of urea concentration in tear fluid with aqueous humour and blood plasma (r = 0.13, p = 0.58 and r = 0.45, p = 0.05 respectively). However, correlation of urea concentration between aqueous humour and blood plasma was highly significant (r = 0.7, p = 0.0001). The concentration of urea in the tear fluid of patients with DES compared to healthy control group was significantly reduced (p < 0.0001).
  
  
  CONCLUSIONS
  Enzymes that are directly involved in the formation of urea are expressed in ocular tissues. This may imply that in the ocular surface is a well-coordinated system of enzymes that can produce urea which might be independent of external urea supply.
authors.affiliation: Department of Anatomy and Cell Biology, Martin Luther University of Halle-Wittenberg, Große Steinstraße, Halle/Saale, Germany. kristin.jaeger@medizin.uni-halle.de
authors.forename: Kristin
authors.initials: K
authors.lastname: Jäger
authors.forename: Heike
authors.initials: H
authors.lastname: Kielstein
authors.forename: Matthias
authors.initials: M
authors.lastname: Dunse
authors.forename: Norbert
authors.initials: N
authors.lastname: Nass
authors.forename: Friedrich
authors.initials: F
authors.lastname: Paulsen
authors.forename: Saadettin
authors.initials: S
authors.lastname: Sel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001082:Aqueous Humor / Q000201:enzymology; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D003228:Conjunctiva / Q000201:enzymology*; D003315:Cornea / Q000201:enzymology*; D015352:Dry Eye Syndromes / Q000201:enzymology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007765:Lacrimal Apparatus / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013666:Tears / Q000378:metabolism*; D014508:Urea / Q000378:metabolism*; D014512:Ureohydrolases / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D014508:Urea; D014512:Ureohydrolases; C574619:ARG1 protein, human; C477631:ARG2 protein, human; D001119:Arginase; C019625:agmatinase