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dc.contributor.author
de Genaro, Pablo Adrian
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dc.contributor.author
Simón, Maria Victoria
dc.contributor.author
Rotstein, Nora Patricia
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dc.contributor.author
Politi, Luis Enrique
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dc.date.available
2016-02-29T18:31:48Z
dc.date.issued
2013-04
dc.identifier.citation
de Genaro, Pablo Adrian; Simón, Maria Victoria; Rotstein, Nora Patricia; Politi, Luis Enrique; Retinoic acid promotes apoptosis and differentiation in photoreceptors by activating the p38 MAP kinase pathway; Association For Research In Vision And Ophthalmology; Investigative Ophthalmology & Visual Science; 54; 4-2013; 3143-3156
dc.identifier.issn
0146-0404
dc.identifier.issn
http://dx.doi.org/10.1167/iovs.12-11049
dc.identifier.uri
http://hdl.handle.net/11336/4521
dc.description.abstract
Purpose Retinoic acid (RA) has a critical role during development of the retina, controlling cell fate and differentiation. We here investigated RA effects on photoreceptor differentiation and apoptosis and the intracellular pathways involved in these effects. Methods Rat retinal neuronal cultures were supplemented with RA and with or without docosahexaenoic acid (DHA), a photoreceptor trophic factor. Photoreceptor apoptosis and differentiation were evaluated at different times of development. The effect of the pan caspase inhibitor Z-VAD-FMK on apoptosis and differentiation was determined. RA activation of p38 MAP kinase was determined by evaluating phosphorylated (P)-p38 levels in cultures with or without RA and the effect of pre-treatment with SB203580, a p38 specific inhibitor. Results RA addition at day 0, when cells were still proliferating, selectively increased apoptosis in photoreceptors, whereas addition at day 2 no longer caused cell death. DHA and Z-VAD-FMK prevented this early apoptosis. RA stimulated opsin and peripherin expression and neurite outgrowth regardless of time of development. RA addition rapidly increased P-p38 levels, whereas p38 inhibition decreased RA-induced differentiation and apoptosis, without affecting neurite outgrowth. Conclusions Our results show that RA stimulated differentiation and induced an early apoptosis in photoreceptors, which were rescued by DHA addition. Noteworthy, activation of the p38 intracellular pathway was required for RA effects on both differentiation and apoptosis. This suggests that RA induction of differentiation during early development must be counterbalanced by survival factors, such as DHA, to prevent photoreceptor death and this interplay might help to establish the final number of photoreceptors.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Association For Research In Vision And Ophthalmology
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Photoreceptors
dc.subject
Retinoic Acid
dc.subject
Apoptosis
dc.subject
Retina
dc.subject.classification
Bioquímica y Biología Molecular
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Retinoic acid promotes apoptosis and differentiation in photoreceptors by activating the p38 MAP kinase pathway
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-03-30 10:35:44.97925-03
dc.journal.volume
54
dc.journal.pagination
3143-3156
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
Rockville, MD 20852
dc.description.fil
Fil: de Genaro, Pablo Adrian. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
dc.description.fil
Fil: Simón, Maria Victoria. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
dc.description.fil
Fil: Rotstein, Nora Patricia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
dc.description.fil
Fil: Politi, Luis Enrique. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
dc.journal.title
Investigative Ophthalmology & Visual Science
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/10.1167/iovs.12-11049
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/ark/http://www.ncbi.nlm.nih.gov/pubmed/23580485
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/ark/http://iovs.arvojournals.org/article.aspx?articleid=2189053
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