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(Investigative Ophthalmology and Visual Science. 2003;44:4682-4688.)
© 2003 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.03-0198
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Protective Effect of D-ß-Hydroxybutyrate on Corneal Epithelia in Dry Eye Conditions through Suppression of Apoptosis

Shigeru Nakamura,1 Michiko Shibuya,1 Yasukazu Saito,1 Hideo Nakashima,1 Fumio Saito,1 Akihiro Higuchi,2 and Kazuo Tsubota2

1From Ophtecs Corporation, Hyogo, Japan; and the 2Department of Ophthalmology, Tokyo Dental College, Chiba, Japan.

PURPOSE. To investigate the effect of D-ß-hydroxybutyrate (HBA) on ocular surface epithelial disorders induced by tear fluid deficiency, the potency of HBA and serum, the efficacy of which has been well documented in clinical application, were compared.

METHODS. Rat corneal epithelial erosion was induced by exposure of rat eyes to continuous low-humidity airflow, which accelerated the tear evaporation. During desiccation, one eye of each rat was treated with HBA (20, 40, or 80 mM) or rat serum (5%, 20%, or 100%), and in the other eye a drop of phosphate-buffered saline (PBS) was instilled as the control. Histopathologic examination and quantification of the epithelial defect area were performed. The apoptosis in the epithelia was determined by chromatin condensation using the Hoechst 33342 fluorescein probe.

RESULTS. In PBS-treated eyes, thinning in the cell layer was seen on the periphery of the initial wound after 6 hours, and it progressed to defects after 12 hours. In the 80-mM HBA and 20% serum applications, the pathologic change in the epithelia was moderate, and the structure was maintained in an almost normal state in the 100% serum application. Significant decreases in the defect areas were observed in the 5%, 20%, and 100% serum and 40- and 80-mM HBA treatment groups compared with the PBS-treated eyes (n = 12). A significant suppression of chromatin condensation was observed with HBA and serum treatment.

CONCLUSIONS. These results suggest the potential clinical application of HBA for ocular surface epithelial disorders to maintain epithelial cell viability in patients with dry eye.




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