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(Investigative Ophthalmology and Visual Science. 2007;48:1102-1109.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-0809

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Protective Effect of Uridine on Cornea in a Rabbit Dry Eye Model

Joo Youn Oh,1,2 Youn Seok In,1,2 Mee Kum Kim,1,2 Jung Hwa Ko,2 Hyun Ju Lee,2 Ki Cheul Shin,3 Sang Mok Lee,1,2 Won Ryang Wee,1,2 Jin Hak Lee,1,2 and Myunggyu Park4

1From the Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea; 2Seoul National University Hospital Clinical Research Institute, Seoul, Korea; 3Department of Ophthalmology, Kunkuk University Hospital, Seoul, Korea; and 4MD Bioalpha, Suwon, Korea.

PURPOSE. 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 104 cells/well) and keratocytes (1 x 104 cells/well) at various concentrations (0.5–50 µM). 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 µM) 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.








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