Protective effect of uridine on cornea in a rabbit dry eye model.
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.
Oh
Joo Youn
JY
Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea.
In
Youn Seok
YS
Kim
Mee Kum
MK
Ko
Jung Hwa
JH
Lee
Hyun Ju
HJ
Shin
Ki Cheul
KC
Lee
Sang Mok
SM
Wee
Won Ryang
WR
Lee
Jin Hak
JH
Park
Myunggyu
M
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
D006025:Glycosaminoglycans; D009883:Ophthalmic Solutions; D009569:Nitric Oxide; D006820:Hyaluronic Acid; D020780:Matrix Metalloproteinase 9; D014529:Uridine