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H. Nakashima, Y. Saitoh, S. Nakamura, F. Saito, A. Higuchi, K. Tubota; Effect of D-3-Hydroxybutyrate (HBA) on Corneal Epithelial Disorder in Dry Eye Condition . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2533. doi: https://doi.org/.
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Purpose: HBA has been shown to ameliorate tissue damage, protein catabolism and metabolic dysfunction in various stress conditions. In this study, we used a rat dry eye model to determine whether topically applied HBA could prevent the pathogenesis of corneal epithelial erosion caused by ocular surface desiccation, and assessed the therapeutic benefit of HBA in ophthalmic formulations, by comparing the potency of HBA with serum, of which the efficacy in clinical application has been well investigated. Methods: Male rats (8 weeks) were placed in a desiccation room to enhance tear evaporation: room temperature 23±2°C, relative humidity 28±2% and constant air flow (2-4 m/s) and maintained for 12 hours, just after bilaterally wounding the central region of the corneal epithelium (0.4 mm2) as a trigger for corneal epithelial erosion. During desiccation, one eye of each rat was treated with HBA (20, 40, 80 mM) or rat serum (5, 20, 100%) and the other eye was given a drop of PBS as a control. Ten microliters of eye drops were given every hour. Histopathological examination of the corneal epithelium was performed after 6 and 12 hours of desiccation. To quantify epithelial defect, images of fluorescein stained corneal surface were applied to image analysis. Results: In PBS treated eyes, thinning in the cell layer accompanied by extensive exfoliation of the corneal epithelium was seen on the periphery of the initial wound after 6 hours, and then these detachments progressed to defects after 12 hours. In the 80 mM HBA and 20% serum applications, the thinning in the cell layer was moderate and the structure was maintained in an almost normal state in the 100% serum application. The defect areas in 20, 40, 80 mM HBA decreased to 104.7% (N.S.), 79.5% (p < 0.05), 65.3% (p < 0.01) of the control, and those in 5, 20, 100% serum decreased to 72.7% (p < 0.05), 53.6% (p < 0.01), 48.5% (p < 0.01) of the control, respectively (n=12). Conclusions: These results suggest a potential therapeutic effect of HBA in the clinical treatment of ocular surface epithelial disorder in patients with dry eye.
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