Inherited photoreceptor degeneration causes the death of melanopsin-positive retinal ganglion cells and increases their coexpression of brn3a
Garcia-Ayuso D ; Di Pierdomenico J ; Esquiva G ; Nadal-Nicolás FM ; Pinilla Lozano, Maria Isabel (Universidad de Zaragoza) ; Cuenca N ; Vidal-Sanz M ; Agudo-Barriuso M ; Villegas-Pérez MP.
Resumen: 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.
Idioma: Inglés
DOI: 10.1167/iovs.15-16808
Año: 2015
Publicado en: INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 56, 8 (2015), 4592-4604
ISSN: 0146-0404
Factor impacto JCR: 3.427 (2015)
Categ. JCR: OPHTHALMOLOGY rank: 6 / 56 = 0.107 (2015) - Q1 - T1
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI13-00643
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI13-01266
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/RETICS-RD12-0034-0010
Financiación: info:eu-repo/grantAgreement/ES/MICINN/ISCIII-RD12-0034-0014
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BFU2012-36845
Financiación: info:eu-repo/grantAgreement/ES/MINECO/SAF-2012-38328
Tipo y forma: Article (Published version)
Área (Departamento): Oftalmología (Departamento de Cirugía, Ginecología y Obstetricia)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
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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.
Idioma: Inglés
DOI: 10.1167/iovs.15-16808
Año: 2015
Publicado en: INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 56, 8 (2015), 4592-4604
ISSN: 0146-0404
Factor impacto JCR: 3.427 (2015)
Categ. JCR: OPHTHALMOLOGY rank: 6 / 56 = 0.107 (2015) - Q1 - T1
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI13-00643
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI13-01266
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/RETICS-RD12-0034-0010
Financiación: info:eu-repo/grantAgreement/ES/MICINN/ISCIII-RD12-0034-0014
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BFU2012-36845
Financiación: info:eu-repo/grantAgreement/ES/MINECO/SAF-2012-38328
Tipo y forma: Article (Published version)
Área (Departamento): Oftalmología (Departamento de Cirugía, Ginecología y Obstetricia)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. 0
Exportado de SIDERAL (2017-01-03-12:03:31)
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