Premium
Pro‐survival redox signalling in progesterone‐mediated retinal neuroprotection
Author(s) -
Ruiz Lopez Ana M.,
Roche Sarah L.,
Wyse Jackson Alice C.,
Moloney Jennifer N.,
Byrne Ashleigh M.,
Cotter Thomas G.
Publication year - 2017
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13604
Subject(s) - neuroprotection , retina , retinitis pigmentosa , retinal , biology , photoreceptor cell , microbiology and biotechnology , endocrinology , medicine , pharmacology , neuroscience , biochemistry
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 ( PGRMC 1); 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.