title: Functional and morphological study of retinal photoreceptor cell degeneration in transgenic rabbits with a Pro347Leu rhodopsin mutation.
abstract: OBJECTIVE
  To investigate the process of retinal degeneration by analyzing the functional and morphological findings in transgenic rabbits with a Pro347Leu rhodopsin mutation.
  
  
  METHODS
  Wild-type (WT) and transgenic (Tg) rabbits at ages 4, 8 and 12 months were used. We conducted functional evaluation by recording the changes in the pupil response to red and blue light stimulation and the amplitude of the electroretinography (ERG). Morphologically, rod and cone distribution was examined using light and electron microscopy. Immunostaining for the identification of retinal ganglion cells (RGCs) was also confirmed by injecting a TUJ-1 monoclonal antibody.
  
  
  RESULTS
  Pupil constriction for infrared pupillography and the a- and b-waves for ERG in Tg rabbits decreased with increasing age; the differences were compared to the age-matched WT rabbits. The subnormal ERG in the Tg rabbits, especially the a-wave decrease and pupil constriction with a long latency time, was induced only during exposure to blue light stimulation at 12 months. Light and electron microscopic findings showed a progressive loss of photoreceptor cells over time manifesting by 8 months in the peripheral retina. Moreover, pyknotic nuclei of the outer nuclear layer in the center of the visual streak were observed. At 12 months, there was disappearance of the rods and ballooning degeneration of the cones. Some remaining RGCs had large cell bodies with long branching dendrites.
  
  
  CONCLUSIONS
  The changes in the pupil light response and amplitude of the ERG could be used to predict the state of retinal degeneration in the Tg rabbit.
authors.affiliation: Department of Orthoptics and Visual Science, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa, 252-0373, Japan. asaken@kitasato-u.ac.jp.
authors.forename: Ken
authors.initials: K
authors.lastname: Asakawa
authors.affiliation: Department of Orthoptics and Visual Science, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa, 252-0373, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishikawa
authors.affiliation: Department of Orthoptics and Visual Science, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa, 252-0373, Japan.
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Uga
authors.affiliation: Department of Ophthalmology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
authors.forename: Kimiyo
authors.initials: K
authors.lastname: Mashimo
authors.affiliation: Department of Ophthalmology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
authors.forename: Kimiya
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Department of Ophthalmology, Mie University Graduate School, School of Medicine, Mie, Japan.
authors.forename: Mineo
authors.initials: M
authors.lastname: Kondo
authors.affiliation: Department of Ophthalmology, Nagoya University Graduate School, School of Medicine, Nagoya, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Terasaki
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D004596:Electroretinography; D008027:Light; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology* / Q000648:ultrastructure; D017354:Point Mutation; D011680:Pupil / Q000528:radiation effects; D011817:Rabbits; D012025:Reflex, Pupillary / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000502:physiology; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000503:physiopathology*; D012243:Rhodopsin / Q000235:genetics*; D014404:Tubulin / Q000378:metabolism
chemical_list: D014404:Tubulin; D012243:Rhodopsin
keywords: Pupil light response; Pyknosis; Rabbit; Retinal photoreceptor cell; Retinitis pigmentosa