Inherited Photoreceptor Degeneration Causes the Death of Melanopsin-Positive Retinal Ganglion Cells and Increases Their Coexpression of Brn3a
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Title: | Inherited Photoreceptor Degeneration Causes the Death of Melanopsin-Positive Retinal Ganglion Cells and Increases Their Coexpression of Brn3a |
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Authors: | 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 |
Research Group/s: | Neurobiología del Sistema Visual y Terapia de Enfermedades Neurodegenerativas (NEUROVIS) |
Center, Department or Service: | Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología |
Keywords: | P23H | Retinitis pigmentosa | Melanopsin | Brn3a | Automated quantification | Intrinsically photosensitive | Photoreceptor degeneration | Intrinsically photosensitive RGCs |
Knowledge Area: | Biología Celular |
Issue Date: | Jul-2015 |
Publisher: | Association for Research in Vision and Ophthalmology (ARVO) |
Citation: | Investigative Ophthalmology & Visual Science. 2015, 56: 4592-4604. doi:10.1167/iovs.15-16808 |
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. |
Sponsor: | Supported by grants from the Spanish Ministry of Economy and Competitiveness: SAF-2012-38328; ISCIII-FEDER “Una manera de hacer Europa” PI13/00643, PI13/01266, and BFU2012-36845, RETICS: RD12/0034/0014, and RD12/0034/0010. |
URI: | http://hdl.handle.net/10045/57937 |
ISSN: | 0146-0404 (Print) | 1552-5783 (Online) |
DOI: | 10.1167/iovs.15-16808 |
Language: | eng |
Type: | info:eu-repo/semantics/article |
Rights: | © 2015 by Association for Research in Vision and Ophthalmology |
Peer Review: | si |
Publisher version: | http://dx.doi.org/10.1167/iovs.15-16808 |
Appears in Collections: | INV - NEUROVIS - Artículos de Revistas |
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File | Description | Size | Format | |
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2015_Garcia-Ayuso_etal_IOVS_final.pdf | Versión final (acceso restringido) | 1,99 MB | Adobe PDF | Open Request a copy |
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