Fractalkine-CX3CR1 signaling is critical for progesterone-mediated neuroprotection in the retina
| dc.contributor.author | Roche, Sarah L. | |
| dc.contributor.author | Wyse-Jackson, Alice C. | |
| dc.contributor.author | Ruiz-Lopez, Ana M. | |
| dc.contributor.author | Byrne, Ashleigh M. | |
| dc.contributor.author | Cotter, Thomas G. | |
| dc.contributor.funder | Science Foundation Ireland | en |
| dc.contributor.funder | Fighting Blindness Ireland | en |
| dc.date.accessioned | 2017-02-27T12:16:07Z | |
| dc.date.available | 2017-02-27T12:16:07Z | |
| dc.date.issued | 2017-02-20 | |
| dc.date.updated | 2017-02-27T12:09:57Z | |
| dc.description.abstract | Retinitis pigmentosa (RP) encompasses a group of retinal diseases resulting in photoreceptor loss and blindness. We have previously shown in the rd10 mouse model of RP, that rd10 microglia drive degeneration of viable neurons. Norgestrel, a progesterone analogue, primes viable neurons against potential microglial damage. In the current study we wished to investigate this neuroprotective effect further. We were particularly interested in the role of fractalkine-CX3CR1 signaling, previously shown to mediate photoreceptor-microglia crosstalk and promote survival in the rd10 retina. Norgestrel upregulates fractalkine-CX3CR1 signaling in the rd10 retina, coinciding with photoreceptor survival. We show that Norgestrel-treated photoreceptor-like cells, 661Ws, and C57 explants modulate rd10 microglial activity in co-culture, resulting in increased photoreceptor survival. Assessment of Norgestrel’s neuroprotective effects when fractalkine was knocked-down in 661 W cells and release of fractalkine was reduced in rd10 explants confirms a crucial role for fractalkine-CX3CR1 signaling in Norgestrel-mediated neuroprotection. To further understand the role of fractalkine in neuroprotection, we assessed the release of 40 cytokines in fractalkine-treated rd10 microglia and explants. In both cases, treatment with fractalkine reduced a variety of pro-inflammatory cytokines. These findings further our understanding of Norgestrel’s neuroprotective properties, capable of modulating harmful microglial activity indirectly through photoreceptors, leading to increased neuroprotection. | en |
| dc.description.status | Peer reviewed | en |
| dc.description.version | Published Version | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.citation | Roche, S. L., Wyse-Jackson, A. C., Ruiz-Lopez, A. M., Byrne, A. M. and Cotter, T. G. (2017) 'Fractalkine-CX3CR1 signaling is critical for progesterone-mediated neuroprotection in the retina', Scientific Reports, 7, pp. 43067. doi:10.1038/srep43067 | en |
| dc.identifier.doi | 10.1038/srep43067 | |
| dc.identifier.endpage | 43067-15 | en |
| dc.identifier.issn | 2045-2322 | |
| dc.identifier.journaltitle | Scientific Reports | en |
| dc.identifier.startpage | 43067-1 | en |
| dc.identifier.uri | https://hdl.handle.net/10468/3696 | |
| dc.identifier.volume | 7 | en |
| dc.language.iso | en | en |
| dc.publisher | Nature Publishing Group | en |
| dc.rights | © The Authors, 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ | en |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en |
| dc.subject | Retinitis pigmentosa (RP) | en |
| dc.subject | Microglia | en |
| dc.subject | Retinal diseases | en |
| dc.title | Fractalkine-CX3CR1 signaling is critical for progesterone-mediated neuroprotection in the retina | en |
| dc.type | Article (peer-reviewed) | en |
