dc.contributor.author	Roche, Sarah L.
dc.contributor.author	Kutsyr, Oksana
dc.contributor.author	Cuenca, Nicolás
dc.contributor.author	Cotter, Thomas G.
dc.contributor.funder	Science Foundation Ireland	en
dc.contributor.funder	Fighting Blindness Ireland	en
dc.contributor.funder	Generalitat Valenciana	en
dc.contributor.funder	Instituto de Salud Carlos III	en
dc.contributor.funder	Ministerio de Economía y Competitividad	en
dc.date.accessioned	2019-09-23T09:43:34Z
dc.date.available	2019-09-23T09:43:34Z
dc.date.issued	2019-07-25
dc.description.abstract	Purpose: Retinitis pigmentosa (RP) refers to a group of inherited blinding retinal diseases, whereby the death of mutated rod photoreceptors is followed closely by the death of cone photoreceptors. Cone cell death can be hugely debilitating as color/daytime vision becomes impaired. Thus, treatments that are effective against cone cell death are urgently needed. Our research has been working toward development of a neuroprotective treatment for RP. We have previously demonstrated significant neuroprotective properties of norgestrel, a progesterone analogue, in the mouse retina. The current study further investigates the potential of norgestrel as a treatment for RP, with a focus on long-term preservation of cone photoreceptors. Methods: Using the well-established rd10 mouse model of RP, we administered a norgestrel-supplemented diet at postnatal day (P)30, following widespread loss of rod photoreceptors and at the outset of cone degeneration. We subsequently assessed cone cell morphology and retinal function at P50, P60, and P80, using immunohistochemistry, electroretinograph recordings, and optomotor testing. Results: While cone cell degeneration was widespread in the untreated rd10 retina, we observed profound preservation of cone photoreceptor morphology in the norgestrel-treated mice for at least 50 days, out to P80. This was demonstrated by up to 28-fold more cone arrestin-positive photoreceptors. This protection transpired to functional preservation at all ages. Conclusions: This work presents norgestrel as an incredibly promising long-term neuroprotective compound for the treatment of RP. Crucially, norgestrel could be used in the mid-late stages of the disease to protect remaining cone cells and help preserve color/daytime vision.	en
dc.description.sponsorship	Fighting Blindness Ireland (FB13COT); Spanish Ministry of Economy and Competitiveness (MINECO-FEDER-BFU2015-67139-R); Carlos III Institute (ISCIII RETICS-FEDER RD16/0008/0016)	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., Kutsyr, O., Cuenca, N. and Cotter, T. G. (2019) 'Norgestrel, a Progesterone Analogue, Promotes Significant Long-Term Neuroprotection of Cone Photoreceptors in a Mouse Model of Retinal Disease', Investigative Ophthalmology & Visual Science, 60(8), pp. 3221-3235. (14pp.) DOI: 10.1167/iovs.19-27246	en
dc.identifier.doi	10.1167/iovs.19-27246	en
dc.identifier.eissn	1552-5783
dc.identifier.endpage	3235	en
dc.identifier.issn	0146-0404
dc.identifier.issued	80	en
dc.identifier.journaltitle	Investigative Ophthalmology & Visual Science	en
dc.identifier.startpage	3221	en
dc.identifier.uri	https://hdl.handle.net/10468/8588
dc.identifier.volume	60	en
dc.language.iso	en	en
dc.publisher	Association for Research in Vision and Ophthalmology	en
dc.relation.project	info:eu-repo/grantAgreement/SFI/SFI Investigator Programme/13/IA/1783/IE/Cell survival signalling mechanisms and drug delivery strategies for retinal neuroprotection/	en
dc.relation.project	info:eu-repo/grantAgreement/NIH/NATIONAL INSTITUTE ON DRUG ABUSE/271201600008C-0-0-1/US/IGF::OT::IGF SBIR PHASE I AWARD TOPIC 158; N01DA-16-1210; POP: 8/1/2016 - 1/31/2017./	en
dc.relation.uri	https://iovs.arvojournals.org/article.aspx?articleid=2739389
dc.rights	©The Authors This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.	en
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0	en
dc.subject	Retinitis pigmentosa	en
dc.subject	Cone photoreceptors	en
dc.subject	Neuroprotection	en
dc.subject	Progesterone	en
dc.subject	Rd10	en
dc.title	Norgestrel, a progesterone analogue, promotes significant long-term neuroprotection of cone photoreceptors in a mouse model of retinal disease	en
dc.type	Article (peer-reviewed)	en

Norgestrel, a progesterone analogue, promotes significant long-term neuroprotection of cone photoreceptors in a mouse model of retinal disease

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