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L. Fernandez-Sanchez, I. Pinilla, L. Campello, M. Idiope, J. Martin-Nieto, N. Cuenca; Tauroursodeoxycholic Acid (TUDCA) Slows Retinal Degeneration in Transgenic P23H Rats. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2195. doi: https://doi.org/.
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Systemic injections of TUDCA have been shown to suppress apoptosis and preserve function and morphology of photoreceptor cells in mouse models of retinal degeneration. The purpose of this study was to investigate the possible preventive effect of TUDCA in the rhodopsin P23H transgenic rat model of autosomal dominant retinitis pigmentosa.
Homozygous P23H line-3 rats were used in this study. Animals (20 days to 4 months old) were injected TUDCA (500 mg/kg, i.p.) once a week. Cryostat vertical sections of retinas were subjected to single and double immunostaining with antibodies to specific neuronal markers. Images were obtained by means of immunofluorescence confocal microscopy. Retinal function was assessed by electroretinogram. NAPDH-diaphorase histochemistry on whole-mount retinas was performed to visualize the retinal vascular network. Apoptotic cells were identified by using the TUNEL assay.
Recoverin and transducin immunoreactivity shows a preservation of photoreceptor inner and outer segments present in the retina of TUDCA-treated rats as compared to vehicle-treated subjects. In the latter the number of rows in the ONL was of 2-3 in the nasal area, 3 in the central retina, and 0-1 rows in the temporal retina. However, in TUDCA-treated animals 3-4 rows of photoreceptors were found in the nasal area, 4-6 in central retina and 2-3 in the temporal area. The number of TUNEL-labeled cells was lower in TUDCA-treated animals as compared with controls, indicating a decrease in apoptotic cells. In 4-month old P23H rats the capillary retinal network was significantly reduced with respect to wild-type SD rats. Even, capillary loops were difficult to visualize in the P23H rat. In contrast, the capillary network of TUDCA-treated animals was similar in appearance to that of SD rats, suggesting a positive effect of this compound on the prevention of retinal degeneration.
TUDCA slows photoreceptor cells degeneration and vascular network disruption in P23H rats. This work indicates that the antiapoptotic action of TUDCA could be potentially useful to retard retinal degeneration in retinitis pigmentosa.
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