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L. Fernandez-Sanchez, G. Esquiva, I. Pinilla, J. Martín-Nieto, N. Cuenca; The Antiapoptotic TUDCA Protects Against Mitochondrial Dysfunction, Glial Cell Changes and Loss of the Capillary Network in the Transgenic Rat Model of Retinitis Pigmentosa P23H. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3721.
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It has been reported that TUDCA prevents the degeneration of photoreceptors in the P23H rat retina. The aim of this study was to study the changes in the vascular network and glial cells (astrocytes, Müller cells and microglia) in the P23H rat retina after administration of the antiapoptotic TUDCA.
For this study homozygous P23H line 3 rats were used. The animals (from 20 days to 4 months) were injected weekly with TUDCA (500 mg, i.p.). Vertical retinal cryostat sections were singly or doubly immunostained for specific markers of microglia, Müller cells and/or astrocytes. Wholemount retinas were subjected to lectin staining to reveal the retinal vascular plexus, and an antibody to GFAP was used to observe its relationship to astrocytes.
In the P23H rat, Müller cells expressed the marker GFAP in response to degeneration of the retina. Activation of microglia was also observed, although there were no differences in the number of these cells in the retina of animals treated with TUDCA compared to untreated controls. The number of astrocytes was higher in the retina of TUDCA-treated animals, which was accompanied by minor degeneration of retinal vessels. The morphology of astrocytes in TUDCA-treated animals was similar to that of wild-type (Sprague-Dawley) rats, whereas in untreated P23H astrocytes exhibited a deteriorated morphology, including changes in the Cajal’s sucker-feet. The immunostaining for different mitochondrial markers revealed that TUDCA prevented the loss of mitochondria in the axon terminals of rods in the OPL and in photoreceptor inner segments.
This work suggests that the neuroprotective effect of TUDCA could be useful to delay photoreceptor loss in retinitis pigmentosa and preserve the capillary network and associated astrocytes. TUDCA is also able to avoid the mitochondrial degeneration that occurs in the P23H rat. Therefore, TUDCA could be potentially useful for the future treatment of retinitis pigmentosa.
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