title: Protective effect of uridine on cornea in a rabbit dry eye model.
abstract: OBJECTIVE
  To investigate the effect of uridine on cultured human corneal epithelial cells and keratocytes in vitro and to evaluate whether the application of uridine-containing eye drops could improve ocular surface health in an in vivo dry eye model.
  
  
  METHODS
  Uridine was added to cultured epithelial cells (3 x 10(4) cells/well) and keratocytes (1 x 10(4) cells/well) at various concentrations (0.5-50 microM). Cytotoxicity was tested with the use of MTT assay, and the cells were assessed for apoptosis with the use of flow cytometry. Expressions of hyaluronic acid (HA), glycosaminoglycan (GAG), nitric oxide (NO), and matrix metalloproteinase (MMP)-9 were measured. In vivo, the degree of reepithelialization was assessed after topical application of uridine (100 microM) in a rabbit corneal wound model. Changes in tear production and conjunctival goblet cell counts were investigated after instillation of various concentrations of uridine-containing eye drops in a rabbit dry eye model.
  
  
  RESULTS
  In vitro, uridine showed no cellular toxicity. It increased the biosynthesis of HA and GAG and reduced MMP-9 levels in cultured corneal epithelial cells and keratocytes. In vivo, uridine enhanced corneal wound healing and significantly increased the number of conjunctival goblet cells in rabbits.
  
  
  CONCLUSIONS
  Uridine can restore the health of the ocular surface in a rabbit corneal wound and dry eye model.
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Joo Youn
authors.initials: JY
authors.lastname: Oh
authors.forename: Youn Seok
authors.initials: YS
authors.lastname: In
authors.forename: Mee Kum
authors.initials: MK
authors.lastname: Kim
authors.forename: Jung Hwa
authors.initials: JH
authors.lastname: Ko
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Ki Cheul
authors.initials: KC
authors.lastname: Shin
authors.forename: Sang Mok
authors.initials: SM
authors.lastname: Lee
authors.forename: Won Ryang
authors.initials: WR
authors.lastname: Wee
authors.forename: Jin Hak
authors.initials: JH
authors.lastname: Lee
authors.forename: Myunggyu
authors.initials: M
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D002470:Cell Survival; D002478:Cells, Cultured; D003228:Conjunctiva / Q000166:cytology / Q000187:drug effects; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D019573:Epithelium, Corneal / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006025:Glycosaminoglycans / Q000378:metabolism; D020397:Goblet Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000633:toxicity; D011817:Rabbits; D014529:Uridine / Q000008:administration & dosage* / Q000633:toxicity; D014945:Wound Healing / Q000187:drug effects
chemical_list: D006025:Glycosaminoglycans; D009883:Ophthalmic Solutions; D009569:Nitric Oxide; D006820:Hyaluronic Acid; D020780:Matrix Metalloproteinase 9; D014529:Uridine