PURPOSE: To evaluate the preventive effect of tauroursodeoxycholic acid (TUDCA) on photoreceptor degeneration, synaptic connectivity and functional activity of the retina in the transgenic P23H rat, an animal model of autosomal dominant retinitis pigmentosa (RP). METHODS: P23H line-3 rats were injected with TUDCA once a week from postnatal day (P)21 to P120, in parallel with vehicle-administered controls. At P120, functional activity of the retina was evaluated by electroretinographic (ERG) recording. The effects of TUDCA on the number, morphology, integrity, and synaptic connectivity of retinal cells were characterized by immunofluorescence confocal microscopy. RESULTS: The amplitude of ERG a- and b-waves was significantly higher in TUDCA-treated animals under both scotopic and photopic conditions than in control animals. In the central area of the retina, TUDCA-treated P23H rats showed threefold more photoreceptors than control animals. The number of TUNEL-positive cells was significantly smaller in TUDCA-treated rats, in which photoreceptor morphology was preserved. Presynaptic and postsynaptic elements, as well as the synaptic contacts between photoreceptors and bipolar or horizontal cells, were preserved in TUDCA-treated P23H rats. Furthermore, in TUDCA-treated rat retinas, the number of both rod bipolar and horizontal cell bodies, as well as the density of their synaptic terminals in the outer plexiform layer, was greater than in control rats. CONCLUSIONS: TUDCA treatment was capable of preserving cone and rod structure and function, together with their contacts with their postsynaptic neurons. The neuroprotective effects of TUDCA make this compound potentially useful for delaying retinal degeneration in RP.
PURPOSE: To evaluate the preventive effect of tauroursodeoxycholic acid (TUDCA) on photoreceptor degeneration, synaptic connectivity and functional activity of the retina in the transgenic P23Hrat, an animal model of autosomal dominant retinitis pigmentosa (RP). METHODS:P23H line-3 rats were injected with TUDCA once a week from postnatal day (P)21 to P120, in parallel with vehicle-administered controls. At P120, functional activity of the retina was evaluated by electroretinographic (ERG) recording. The effects of TUDCA on the number, morphology, integrity, and synaptic connectivity of retinal cells were characterized by immunofluorescence confocal microscopy. RESULTS: The amplitude of ERG a- and b-waves was significantly higher in TUDCA-treated animals under both scotopic and photopic conditions than in control animals. In the central area of the retina, TUDCA-treated P23Hrats showed threefold more photoreceptors than control animals. The number of TUNEL-positive cells was significantly smaller in TUDCA-treated rats, in which photoreceptor morphology was preserved. Presynaptic and postsynaptic elements, as well as the synaptic contacts between photoreceptors and bipolar or horizontal cells, were preserved in TUDCA-treated P23Hrats. Furthermore, in TUDCA-treated rat retinas, the number of both rod bipolar and horizontal cell bodies, as well as the density of their synaptic terminals in the outer plexiform layer, was greater than in control rats. CONCLUSIONS:TUDCA treatment was capable of preserving cone and rod structure and function, together with their contacts with their postsynaptic neurons. The neuroprotective effects of TUDCA make this compound potentially useful for delaying retinal degeneration in RP.
Authors: Matthew M LaVail; Shimpei Nishikawa; Roy H Steinberg; Muna I Naash; Jacque L Duncan; Nikolaus Trautmann; Michael T Matthes; Douglas Yasumura; Cathy Lau-Villacorta; Jeannie Chen; Ward M Peterson; Haidong Yang; John G Flannery Journal: Exp Eye Res Date: 2017-11-06 Impact factor: 3.467
Authors: Arlene V Drack; Alina V Dumitrescu; Sajag Bhattarai; Daniel Gratie; Edwin M Stone; Robert Mullins; Val C Sheffield Journal: Invest Ophthalmol Vis Sci Date: 2012-01-05 Impact factor: 4.799
Authors: Laura Fernández-Sánchez; Luis Pérez de Sevilla Müller; Nicholas C Brecha; Nicolás Cuenca Journal: Invest Ophthalmol Vis Sci Date: 2014-08-12 Impact factor: 4.799
Authors: Laura Fernández-Sánchez; Pedro Lax; Carolina Isiegas; Eduard Ayuso; José M Ruiz; Pedro de la Villa; Fatima Bosch; Enrique J de la Rosa; Nicolás Cuenca Journal: Hum Gene Ther Date: 2012-11-05 Impact factor: 5.695