title: Inherited Photoreceptor Degeneration Causes the Death of Melanopsin-Positive Retinal Ganglion Cells and Increases Their Coexpression of Brn3a.
abstract: OBJECTIVE
  To study the population of intrinsically photosensitive retinal ganglion cells (melanopsin-expressing RGCs, m+RGCs) in P23H-1 rats, a rat model of inherited photoreceptor degeneration.
  
  
  METHODS
  At postnatal (P) times P30, P365, and P540, retinas from P23H dystrophic rats (line 1, rapid degeneration; and line 3, slow degeneration) and Sprague Dawley (SD) rats (control) were dissected as whole-mounts and immunodetected for melanopsin and/or Brn3a. The dendritic arborization of m+RGCs and the numbers of Brn3a+RGCs and m+RGCs were quantified and their retinal distribution and coexpression analyzed.
  
  
  RESULTS
  In SD rats, aging did not affect the population of Brn3a+RGCs or m+RGCs or the percentage that showed coexpression (0.27%). Young P23H-1 rats had a significantly lower number of Brn3a+RGCs and showed a further decline with age. The population of m+RGCs in young P23H-1 rats was similar to that found in SD rats and decreased by 22.6% and 28.2% at P365 and P540, respectively, similarly to the decrease of the Brn3a+RGCs. At these ages the m+RGCs showed a decrease of their dendritic arborization parameters, which was similar in both the P23H-1 and P23H-3 lines. The percentage of coexpression of Brn3a was, however, already significantly higher at P30 (3.31%) and increased significantly with age (10.65% at P540).
  
  
  CONCLUSIONS
  Inherited photoreceptor degeneration was followed by secondary loss of Brn3a+RGCs and m+RGCs. Surviving m+RGCs showed decreased dendritic arborization parameters and increased coexpression of Brn3a and melanopsin, phenotypic and molecular changes that may represent an effort to resist degeneration and/or preferential survival of m+RGCs capable of synthesizing Brn3a.
authors.affiliation: Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca (IMIB-Virgen de la Arrixaca) and Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: García-Ayuso
authors.affiliation: Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca (IMIB-Virgen de la Arrixaca) and Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.
authors.forename: Johnny
authors.initials: J
authors.lastname: Di Pierdomenico
authors.affiliation: Departamento de Fisiología, Genética y Microbiología, Universidad de Alicante, San Vicente del Raspeig, Alicante, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Esquiva
authors.affiliation: Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca (IMIB-Virgen de la Arrixaca) and Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.
authors.forename: Francisco Manuel
authors.initials: FM
authors.lastname: Nadal-Nicolás
authors.affiliation: Servicio de Oftalmología, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Pinilla
authors.affiliation: Departamento de Fisiología, Genética y Microbiología, Universidad de Alicante, San Vicente del Raspeig, Alicante, Spain.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Cuenca
authors.affiliation: Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca (IMIB-Virgen de la Arrixaca) and Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Vidal-Sanz
authors.affiliation: Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca (IMIB-Virgen de la Arrixaca) and Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Agudo-Barriuso
authors.affiliation: Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca (IMIB-Virgen de la Arrixaca) and Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.
authors.forename: María P
authors.initials: MP
authors.lastname: Villegas-Pérez
mesh_terms: D000818:Animals; D016923:Cell Death; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007124:Immunoenzyme Techniques; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology*; D017299:Rod Opsins; D050819:Transcription Factor Brn-3A / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D000099210:Melanopsin
chemical_list: D017299:Rod Opsins; D050819:Transcription Factor Brn-3A; D000099210:Melanopsin