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Phosphodiesterase inhibition induces retinal degeneration, oxidative stress and inflammation in cone-enriched cultures of porcine retina.

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Phosphodiesterase inhibition induces retinal degeneration, oxidative stress and inflammation in cone-enriched cultures of porcine retina.

dc.contributor.author	Martínez Fernández de la Cámara, Cristina
dc.contributor.author	Sequedo, María Dolores
dc.contributor.author	Gómez Pinedo, Ulises
dc.contributor.author	Jaijo, Teresa
dc.contributor.author	Aller Mañas, Elena
dc.contributor.author	García Tárraga, Patricia
dc.contributor.author	García Verdugo, José Manuel
dc.contributor.author	Millán Salvador, José María
dc.contributor.author	Rodrigo, Regina
dc.date.accessioned	2014-01-23T11:42:02Z
dc.date.available	2014-01-23T11:42:02Z
dc.date.issued	2013
dc.identifier.citation	Martínez-Fernández de la Cámara, Cristina Sequedo, María Dolores Gómez-Pinedo, Ulises Jaijo, Teresa Aller, Elena García Tárraga, Patricia García Verdugo, José Manuel Millán, José María Rodrigo, Regina 2013 Phosphodiesterase inhibition induces retinal degeneration, oxidative stress and inflammation in cone-enriched cultures of porcine retina. Experimental Eye Research 9 111 122 133
dc.identifier.uri	http://hdl.handle.net/10550/32581
dc.description.abstract	nherited retinal degenerations affecting both rod and cone photoreceptors constitute one of the causes 74 of incurable blindness in the developed world. Cyclic guanosine monophosphate (cGMP) is crucial in the 75 phototransduction and, mutations in genes related to its metabolism are responsible for different retinal 76 dystrophies. cGMP-degrading phosphodiesterase 6 (PDE6) mutations cause around 4e5% of the retinitis 77 pigmentosa, a rare form of retinal degeneration. The aim of this study was to evaluate whether phar- 78 macological PDE6 inhibition induced retinal degeneration in cone-enriched cultures of porcine retina 79 similar to that found in murine models. PDE6 inhibition was induced in cone-enriched retinal explants 80 from pigs by Zaprinast. PDE6 inhibition induced cGMP accumulation and triggered retinal degeneration, 81 as determined by TUNEL assay. Western blot analysis and immunostaining indicated that degeneration 82 was accompanied by caspase-3, calpain-2 activation and poly (ADP-ribose) accumulation. Oxidative stress 83 markers, total antioxidant capacity, thiobarbituric acid reactive substances (TBARS) and nitric oxide 84 measurements revealed the presence of oxidative damage. Elevated TNF-alpha and IL-6, as determined by enzyme immunoassay, were also found in cone-enriched retinal explants treated with Zaprinast. Our 85 study suggests that this ex vivo model of retinal degeneration in porcine retina could be an alternative 86 model for therapeutic research into the mechanisms of photoreceptor death in cone-related diseases, 87 thus replacing or reducing animal experiments.
dc.relation.ispartof	Experimental Eye Research, 2013, vol. 9, num. 111, p. 122-133
dc.subject	Estrès oxidatiu
dc.subject	Retina
dc.subject	Neurociències
dc.title	Phosphodiesterase inhibition induces retinal degeneration, oxidative stress and inflammation in cone-enriched cultures of porcine retina.
dc.type	journal article	es_ES
dc.date.updated	2014-01-23T11:42:02Z
dc.identifier.doi	10.1016/j.exer.2013.03.015
dc.identifier.idgrec	085212
dc.rights.accessRights	open access	es_ES
dc.identifier.url	10.1016/j.exer.2013.03.015