Pro-survival redox signalling in progesterone-mediated retinal neuroprotection

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dc.contributor.authorRuiz López, Ana M.
dc.contributor.authorRoche, Sarah L.
dc.contributor.authorWyse-Jackson, Alice C.
dc.contributor.authorMoloney, Jennifer N.
dc.contributor.authorByrne, Ashleigh M.
dc.contributor.authorCotter, Thomas G.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderFighting Blindness, Ireland
dc.date.accessioned2017-08-31T10:42:00Z
dc.date.available2017-08-31T10:42:00Z
dc.date.issued2017-06-08
dc.date.updated2017-08-30T12:15:04Z
dc.description.abstractRetinitis pigmentosa (RP) is a group of hereditary retinal diseases, characterised by photoreceptor cell loss. Despite a substantial understanding of the mechanisms leading to cell death, an effective therapeutic strategy is sought. Our laboratory has previously demonstrated the neuroprotective properties of Norgestrel, a progesterone analogue, in the degenerating retina, mediated in part by the neurotrophic factor basic fibroblast growth factor (bFGF). In other retinal studies, we have also presented a pro-survival role for reactive oxygen species (ROS), downstream of bFGF. Thus, we hypothesized that Norgestrel utilises bFGF-driven ROS production to promote photoreceptor survival. Using the 661W photoreceptor-like cell line, we now show that Norgestrel, working through progesterone receptor membrane complex 1 (PGRMC1); generates an early burst of pro-survival bFGF-induced ROS. Using the rd10 mouse model of RP, we confirm that Norgestrel induces a similar early pro-survival increase in retinal ROS. Norgestrel-driven protection in the rd10 retina was attenuated in the presence of antioxidants. This study therefore presents an essential role for ROS signalling in Norgestrel-mediated neuroprotection in vitro and demonstrates that Norgestrel employs a similar pro-survival mechanism in the degenerating retina.en
dc.description.sponsorshipScience Foundation Ireland (grant no. 13/IA/1783)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationRuiz Lopez, A. M., Roche, S. L., Wyse Jackson, A. C., Moloney, J. N., Byrne, A. M. and Cotter, T. G. (2017) 'Pro-survival redox signalling in progesterone-mediated retinal neuroprotection', European Journal of Neuroscience, 46(1), pp. 1663-1672. doi:10.1111/ejn.13604en
dc.identifier.doi10.1111/ejn.13604
dc.identifier.endpage1672en
dc.identifier.issn1460-9568
dc.identifier.issued1en
dc.identifier.journaltitleEuropean Journal of Neuroscienceen
dc.identifier.startpage1663en
dc.identifier.urihttps://hdl.handle.net/10468/4595
dc.identifier.volume46en
dc.language.isoenen
dc.publisherJohn Wiley & Sons, Inc.en
dc.rights© 2017, Federation of European Neuroscience Societies and John Wiley & Sons Ltd. This is the peer reviewed version of the following article: Ruiz Lopez, A. M., Roche, S. L., Wyse Jackson, A. C., Moloney, J. N., Byrne, A. M. and Cotter, T. G. (2017) 'Pro-survival redox signalling in progesterone-mediated retinal neuroprotection', European Journal of Neuroscience, 46(1), pp. 1663-1672, which has been published in final form at http://dx.doi.org/10.1111/ejn.13604. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.en
dc.subject661Wen
dc.subjectBasic fibroblast growth factoren
dc.subjectNorgestrelen
dc.subjectPro-survival ROSen
dc.subjectrd10en
dc.titlePro-survival redox signalling in progesterone-mediated retinal neuroprotectionen
dc.typeArticle (peer-reviewed)en
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