García Ayuso, Diego, Di Pierdomenico, Johnny, Esquiva, Gema, Nadal-Nicolás, Francisco Manuel, Pinilla Lozano, Isabel, Cuenca, Nicolás, Vidal Sanz, Manuel, Agudo Barriuso, Marta, Villegas Pérez, María Paz
Inherited Photoreceptor Degeneration Causes the Death of Melanopsin-Positive Retinal Ganglion Cells and Increases Their Coexpression of Brn3a
Investigative Ophthalmology & Visual Science. 2015, 56: 4592-4604. doi:10.1167/iovs.15-16808
URI: http://hdl.handle.net/10045/57937
DOI: 10.1167/iovs.15-16808
ISSN: 0146-0404 (Print)
Abstract: 
Purpose: 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.
Keywords:P23H, Retinitis pigmentosa, Melanopsin, Brn3a, Automated quantification, Intrinsically photosensitive, Photoreceptor degeneration, Intrinsically photosensitive RGCs
Association for Research in Vision and Ophthalmology (ARVO)
info:eu-repo/semantics/article