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Pro-survival redox signalling in progesterone-mediated retinal neuroprotection
Ruiz López, Ana M.
Roche, Sarah L.
Wyse-Jackson, Alice C.
Moloney, Jennifer N.
Byrne, Ashleigh M.
Cotter, Thomas G.
John Wiley & Sons, Inc.
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.
661W , Basic fibroblast growth factor , Norgestrel , Pro-survival ROS , rd10
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
© 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.