[HTML][HTML] TUDCA slows retinal degeneration in two different mouse models of retinitis pigmentosa and prevents obesity in Bardet-Biedl syndrome type 1 mice

AV Drack, AV Dumitrescu, S Bhattarai… - … & visual science, 2012 - iovs.arvojournals.org
AV Drack, AV Dumitrescu, S Bhattarai, D Gratie, EM Stone, R Mullins, VC Sheffield
Investigative ophthalmology & visual science, 2012iovs.arvojournals.org
Purpose.: To evaluate and compare the protective effect of tauroursodeoxycholic acid
(TUDCA) on photoreceptor degeneration in different models of retinal degeneration (RD) in
mice. Methods.: Bbs M390R/M390R mice were injected subcutaneously twice a week, from
P40 to P120, and rd10 mice were injected every 3 days from P6 to P38 with TUDCA or
vehicle (0.15 M NaHCO 3). Rd1 and rd16 mice were injected daily from P6 to P30 with
TUDCA or vehicle. Retinal structure and function were determined at multiple time points by …
Abstract
Purpose.: To evaluate and compare the protective effect of tauroursodeoxycholic acid (TUDCA) on photoreceptor degeneration in different models of retinal degeneration (RD) in mice.
Methods.: Bbs M390R/M390R mice were injected subcutaneously twice a week, from P40 to P120, and rd10 mice were injected every 3 days from P6 to P38 with TUDCA or vehicle (0.15 M NaHCO 3). Rd1 and rd16 mice were injected daily from P6 to P30 with TUDCA or vehicle. Retinal structure and function were determined at multiple time points by electroretinography (ERG), optical coherence tomography (OCT), and histology.
Results.: The amplitude of ERG b-waves was significantly higher in TUDCA-treated Bbs1 and rd10 animals than in controls. Retinal thickness on OCT was slightly greater in treated Bbs1 animals than in the controls. Histologically, outer segments were preserved, and the outer nuclear layer was significantly thicker in the treated Bbs1 and rd10 mice than in the controls. Bbs1 M390R/M390R mice developed less obesity than the control Bbs1 M390R/M390R while receiving TUDCA. The Rd1 and rd16 mice showed no improvement with TUDCA treatment, and the rd1 mice did not have normal weight gain during treatment.
Conclusions.: TUDCA treatment preserved ERG b-waves and the outer nuclear layer in Bbs1 M390R/M390R mice, and prevented obesity assessed at P120. TUDCA treatment preserved ERG b-waves and the outer nuclear layer in the rd10 mice to P30. TUDCA is a prime candidate for treatment of humans with retinal degeneration, especially those with Bardet-Biedl syndrome, whom it may help not only with the vision loss, but with the debilitating obesity as well.
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