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(Investigative Ophthalmology and Visual Science. 2005;46:2379-2387.)
© 2005 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.04-1344
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D-ß-Hydroxybutyrate Protects against Corneal Epithelial Disorders in a Rat Dry Eye Model with Jogging Board

Shigeru Nakamura,1 Michiko Shibuya,1 Hideo Nakashima,1 Tomohiro Imagawa,2 Masato Uehara,2 and Kazuo Tsubota3

1From the Ophtecs Corporation, Hyogo, Japan; the 2Department of Veterinary Anatomy, Faculty of Agriculture, Tottori University, Tottori, Japan; and the 3Department of Ophthalmology, Keio University, School of Medicine, Tokyo, Japan.

PURPOSE. The purpose of this study was to establish a rat dry eye model of corneal epithelial disorders by inducing improper tear dynamics and change in blink frequency. The protective effect of D-ß-hydroxybutyrate (HBA) on the corneal epithelia was also investigated.

METHODS. A series of treatments were performed under continuous exposure to low-humidity airflow. Rats were placed on a jogging board (JB) made of a plastic pipe for 7.5 h/d, and, for 16.5 hours, they were placed in individual cages without JB treatment. The resultant changes in tear dynamics and corneal epithelial structure were then analyzed. Five days after the rats were exposed to the treatment, eyes that showed corneal fluorescein staining were examined, to investigate the effect of HBA, by administration of eye drops containing 80 mM HBA four times daily during JB treatment for 5 days.

RESULTS. Significant reductions in blink frequency, Schirmer score, and tear clearance were recorded during JB treatment in eyes that showed persistent punctate staining of almost one half of the corneal surface. The application of HBA-containing eye drops significantly reduced the punctate staining compared with the initial or phosphate-buffered saline–treated eyes.

CONCLUSIONS. This rat dry eye model, established by repeated JB treatment in desiccating conditions, induced abnormal tear dynamics and superficial punctate keratopathy similar to that in humans. These findings suggest the potential clinical application of HBA in corneal surface epithelial disorders in patients with moderate to mild dry eye.




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