Pro-survival redox signalling in progesterone-mediated retinal neuroprotection

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dc.contributor.author Ruiz Lopez, Ana M.
dc.contributor.author Roche, Sarah L.
dc.contributor.author Wyse-Jackson, Alice C.
dc.contributor.author Moloney, Jennifer N.
dc.contributor.author Byrne, Ashleigh M.
dc.contributor.author Cotter, Thomas G.
dc.date.accessioned 2017-08-31T10:42:00Z
dc.date.available 2017-08-31T10:42:00Z
dc.date.issued 2017-06-08
dc.identifier.citation 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. doi:10.1111/ejn.13604 en
dc.identifier.volume 46 en
dc.identifier.issued 1 en
dc.identifier.startpage 1663 en
dc.identifier.endpage 1672 en
dc.identifier.issn 1460-9568
dc.identifier.uri http://hdl.handle.net/10468/4595
dc.identifier.doi 10.1111/ejn.13604
dc.description.abstract Retinitis 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.sponsorship Science Foundation Ireland (grant no. 13/IA/1783) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher John 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.subject 661W en
dc.subject Basic fibroblast growth factor en
dc.subject Norgestrel en
dc.subject Pro-survival ROS en
dc.subject rd10 en
dc.title Pro-survival redox signalling in progesterone-mediated retinal neuroprotection en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Thomas Cotter, School Of Biochemistry & Cell Biology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: t.cotter@ucc.ie en
dc.internal.availability Full text available en
dc.check.info Access to this article is restricted until 12 months after publication by request of the publisher. en
dc.check.date 2018-06-08
dc.date.updated 2017-08-30T12:15:04Z
dc.description.version Accepted Version en
dc.internal.rssid 409120267
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Fighting Blindness, Ireland
dc.description.status Peer reviewed en
dc.identifier.journaltitle European Journal of Neuroscience en
dc.internal.copyrightchecked Yes en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress t.cotter@ucc.ie en


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