title: Tauroursodeoxycholic acid prevents retinal degeneration in transgenic P23H rats.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Physiology, Genetics and Microbiology, Universidad de Alicante, CampusUniversitario San Vicente, Alicante, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Fernández-Sánchez
authors.forename: Pedro
authors.initials: P
authors.lastname: Lax
authors.forename: Isabel
authors.initials: I
authors.lastname: Pinilla
authors.forename: José
authors.initials: J
authors.lastname: Martín-Nieto
authors.forename: Nicolás
authors.initials: N
authors.lastname: Cuenca
mesh_terms: D000818:Animals; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D055253:Color Vision; D004195:Disease Models, Animal; D004596:Electroretinography; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D018613:Microscopy, Confocal; D055254:Night Vision; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects; D051381:Rats; D055647:Rats, Transgenic; D051245:Retinal Bipolar Cells / Q000187:drug effects; D012162:Retinal Degeneration / Q000503:physiopathology / Q000517:prevention & control*; D013655:Taurochenodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D002756:Cholagogues and Choleretics; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine