Knockout of CaV1.3 L-type calcium channels in a mouse model of retinitis pigmentosa

Abstract Retinitis Pigmentosa is a genetically heterogeneous, degenerative retinal disorder characterized by gradual dysfunction and death of photoreceptors, first rods and later cones, and progressive blindness. Studies suggested that application of L-type calcium channel blockers rescues photorece...

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Autores principales:	Irem Kilicarslan, Lucia Zanetti, Elena Novelli, Christoph Schwarzer, Enrica Strettoi, Alexandra Koschak
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c195843478044d28b924edd3054a2ac5
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spelling	oai:doaj.org-article:c195843478044d28b924edd3054a2ac52021-12-02T18:46:57ZKnockout of CaV1.3 L-type calcium channels in a mouse model of retinitis pigmentosa10.1038/s41598-021-94304-32045-2322https://doaj.org/article/c195843478044d28b924edd3054a2ac52021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94304-3https://doaj.org/toc/2045-2322Abstract Retinitis Pigmentosa is a genetically heterogeneous, degenerative retinal disorder characterized by gradual dysfunction and death of photoreceptors, first rods and later cones, and progressive blindness. Studies suggested that application of L-type calcium channel blockers rescues photoreceptors in paradigms related to Ca2+ overflow. To investigate whether Cav1.3 L-type channels have protective effects in the retina, we established a new mouse model by crossing rd10, modeling autosomal-recessive RP, with Cav1.3 deficient mice (rd10/Cav1.3KO). Our immunohistochemical analyses revealed an influence of Cav1.3 channels on the degenerative process of photoreceptors. The absence of Cav1.3 delayed the centre-to-periphery degeneration of rods indicated by a significantly higher number of photoreceptor rows and, consequently, of cones. In accordance with a preserved number of cones we observed a regular row of cone somas in rd10/Cav1.3-KO retinas. Surviving rod photoreceptors maintained synaptic contacts with rod bipolar cells. However, the delay in degeneration was only observed up to postnatal day 45. Although we observed a reduction in the spontaneous oscillatory retinal activity during multielectrode array analyses, measurable functional preservation was lacking in behavioural tests. In conclusion, Cav1.3 channels contribute to photoreceptor degeneration in rd10 retinas but photoreceptor temporary rescue might rather be achieved indirectly through other retinal cell layers.Irem KilicarslanLucia ZanettiElena NovelliChristoph SchwarzerEnrica StrettoiAlexandra KoschakNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Irem Kilicarslan Lucia Zanetti Elena Novelli Christoph Schwarzer Enrica Strettoi Alexandra Koschak Knockout of CaV1.3 L-type calcium channels in a mouse model of retinitis pigmentosa
description	Abstract Retinitis Pigmentosa is a genetically heterogeneous, degenerative retinal disorder characterized by gradual dysfunction and death of photoreceptors, first rods and later cones, and progressive blindness. Studies suggested that application of L-type calcium channel blockers rescues photoreceptors in paradigms related to Ca2+ overflow. To investigate whether Cav1.3 L-type channels have protective effects in the retina, we established a new mouse model by crossing rd10, modeling autosomal-recessive RP, with Cav1.3 deficient mice (rd10/Cav1.3KO). Our immunohistochemical analyses revealed an influence of Cav1.3 channels on the degenerative process of photoreceptors. The absence of Cav1.3 delayed the centre-to-periphery degeneration of rods indicated by a significantly higher number of photoreceptor rows and, consequently, of cones. In accordance with a preserved number of cones we observed a regular row of cone somas in rd10/Cav1.3-KO retinas. Surviving rod photoreceptors maintained synaptic contacts with rod bipolar cells. However, the delay in degeneration was only observed up to postnatal day 45. Although we observed a reduction in the spontaneous oscillatory retinal activity during multielectrode array analyses, measurable functional preservation was lacking in behavioural tests. In conclusion, Cav1.3 channels contribute to photoreceptor degeneration in rd10 retinas but photoreceptor temporary rescue might rather be achieved indirectly through other retinal cell layers.
format	article
author	Irem Kilicarslan Lucia Zanetti Elena Novelli Christoph Schwarzer Enrica Strettoi Alexandra Koschak
author_facet	Irem Kilicarslan Lucia Zanetti Elena Novelli Christoph Schwarzer Enrica Strettoi Alexandra Koschak
author_sort	Irem Kilicarslan
title	Knockout of CaV1.3 L-type calcium channels in a mouse model of retinitis pigmentosa
title_short	Knockout of CaV1.3 L-type calcium channels in a mouse model of retinitis pigmentosa
title_full	Knockout of CaV1.3 L-type calcium channels in a mouse model of retinitis pigmentosa
title_fullStr	Knockout of CaV1.3 L-type calcium channels in a mouse model of retinitis pigmentosa
title_full_unstemmed	Knockout of CaV1.3 L-type calcium channels in a mouse model of retinitis pigmentosa
title_sort	knockout of cav1.3 l-type calcium channels in a mouse model of retinitis pigmentosa
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c195843478044d28b924edd3054a2ac5
work_keys_str_mv	AT iremkilicarslan knockoutofcav13ltypecalciumchannelsinamousemodelofretinitispigmentosa AT luciazanetti knockoutofcav13ltypecalciumchannelsinamousemodelofretinitispigmentosa AT elenanovelli knockoutofcav13ltypecalciumchannelsinamousemodelofretinitispigmentosa AT christophschwarzer knockoutofcav13ltypecalciumchannelsinamousemodelofretinitispigmentosa AT enricastrettoi knockoutofcav13ltypecalciumchannelsinamousemodelofretinitispigmentosa AT alexandrakoschak knockoutofcav13ltypecalciumchannelsinamousemodelofretinitispigmentosa
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Knockout of CaV1.3 L-type calcium channels in a mouse model of retinitis pigmentosa

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