Purchase this article with an account.
L. Fernandez-Sanchez, P. Lax, G. Esquiva, I. Pinilla, J. Martín-Nieto, N. Cuenca; Loss of Synaptic Contacts in the Retina Is Prevented by Tauroursodeoxycholic Acid (TUDCA) in Transgenic P23H Rats. Invest. Ophthalmol. Vis. Sci. 2009;50(13):980.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
It has been seen that systemic injections of TUDCA are neuroprotective in mouse and rat models of retinal degenerations. This compound is capable of preventing the loss of rod photoreceptors and electroretinographic (ERG) response in different animal models of retinopathy and light-induced visual function loss. The aim of this study was to evaluate its effects on synaptic connectivity, cone morphology, ERG response and retinal capillary nerwork in the rhodopsin P23H transgenic rat model of dominant retinitis pigmentosa.
Homozygous P23H line-3 rats were used in this study. Animals were injected with TUDCA (500 mg/kg, i.p.) once a week from 20 days until 4 months postnatally. Cryostat vertical sections were subjected to single or double immunostaining with specific neuronal markers and visualized by confocal microscopy. NADPH diaphorase histochemistry on whole-mount retinas was performed to analyze the extent of capillary-network protection. ERGs were recorded at the end of treatments.
In P23H rats TUDCA prevented degeneration of cone photoreceptors, these exhibiting a good preserved morphology. Double immunolabeling for synaptophysin, calbindin and PKC showed a conservation of synaptic connectivity between photoreceptors and bipolar and horizontal cells in the outer plexiform layer of TUDCA-treated rats, as compared to control animals. The ERG waves amplitude in TUDCA-treated P23H was significantly higher than in vehicle-treated rats, which confirms the preservation of functionality and structure of photoreceptors. Furthermore, TUDCA-treated animals exhibited conserved areas of the retinal capillary network that were lost in 4 month-old control rats.
TUDCA is capable of preserving cone and rod structure and function, together with their contacts with postsynaptic cells, in P23H transgenic rats. This work suggests that the neuroprotective effect of TUDCA could be useful to delay photoreceptor loss and preserve the capillary network in retinitis pigmentosa.
This PDF is available to Subscribers Only