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 I (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

Factor impacto SCIMAGO: 2.011 - Ophthalmology (Q1) - Sensory Systems (Q1) - Cellular and Molecular Neuroscience (Q2)

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: Artículo (Versión definitiva)

Área (Departamento): Área Oftalmología (Dpto. Cirugía,Ginecol.Obstetr.)