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S. S. Sidney, C. Kendall, J. H. Boatright, M. T. Pardue, J. M. Nickerson; Effect of Tauroursodeoxycholic Acid (TUDCA) in Rd10 Mice: A Dose-Response Study. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3225.
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© ARVO (1962-2015); The Authors (2016-present)
Previous experiments have shown that tauroursodeoxycholic acid (TUDCA) slows retinal degeneration in the rd10 mouse at a single, relatively high concentration. As part of the pre-clinical testing of this compound, we're interested in determining the minimal effective dose in this model. The purpose of this study is to show the efficacy of various doses of TUDCA in preserving the electroretinogram (ERG) response in rd10 mice.
rd10 mice were subcutaneously injected with TUDCA in sodium bicarbonate buffer at various concentrations (0, 100, 250, 500 mg drug/kg mouse body weight, final concentrations) every three days starting at postnatal day (P) 6 and continuing until P18. At P18, electroretinograms (ERGs) were used to assess visual function in rd10 mice as well as age-matched c57/bl6 mice. Scotopic (dark-adapted) and photopic (light-adapted) ERG measures were taken at 139 cd sec/m2 and 79 cd sec/m2 flash intensities, respectively. Mean data were analyzed by ANOVA and Student-Newman-Keuls post hoc testing.
Scotopic and photopic ERG amplitudes of vehicle-treated rd10 mice were significantly lower than those of c57/bl6 mice. Treatment of rd10 mice with increasing concentrations of TUDCA produced increasing ERG amplitudes. rd10 mice treated with any of the three concentrations of TUDCA had greater scotopic a-wave and b-wave ERG amplitudes than vehicle-treated mice. Photopic ERG amplitudes, though increasing in mice receiving increased drug concentrations, were not statistically significantly different from those of vehicle-treated mice.
TUDCA treatment preserved photoreceptor function in a dose-dependent manner, producing a significant elevation of ERG amplitudes even at the lowest concentration tested.
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