{"id":8986,"date":"2025-08-29T18:56:18","date_gmt":"2025-08-29T16:56:18","guid":{"rendered":"https:\/\/rvh-synergie.org\/actualites\/les-modeles-de-souris-de-la-retinite-pigmentosa-refletent-la-pathobiologie-du-rp59-humain\/"},"modified":"2025-08-29T18:56:21","modified_gmt":"2025-08-29T16:56:21","slug":"les-modeles-de-souris-de-la-retinite-pigmentosa-refletent-la-pathobiologie-du-rp59-humain","status":"publish","type":"post","link":"https:\/\/rvh-synergie.org\/actualites\/les-modeles-de-souris-de-la-retinite-pigmentosa-refletent-la-pathobiologie-du-rp59-humain\/","title":{"rendered":"Les mod\u00e8les de souris de la r\u00e9tinite pigmentosa refl\u00e8tent la pathobiologie du RP59 humain"},"content":{"rendered":"
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La d\u00e9g\u00e9n\u00e9rescence r\u00e9tinienne de la r\u00e9tinite pigmentaire est caus\u00e9e par une famille de mutations h\u00e9r\u00e9ditaires dans pr\u00e8s de 100 g\u00e8nes qui conduisent lentement \u00e0 la c\u00e9cit\u00e9 au fil des ann\u00e9es ou des d\u00e9cennies.<\/p>\n

L’un de ces g\u00e8nes code pour l’enzyme DHDDS, une partie de la voie qui glycosylate les prot\u00e9ines dans des cellules plus \u00e9lev\u00e9es. La r\u00e9tinite pigmentaire des mutations DHDDS est appel\u00e9e RP59. Il s’agit d’une maladie g\u00e9n\u00e9tique r\u00e9cessive, ce qui signifie que des mutations doivent \u00eatre pr\u00e9sentes sur les deux copies du g\u00e8ne DHDDS pour provoquer une maladie.<\/p>\n

Pour mieux comprendre et potentiellement traiter RP59, Steven Pittler, Ph.D., et ses coll\u00e8gues de l’Universit\u00e9 de l’Alabama \u00e0 Birmingham ont cr\u00e9\u00e9 de nouveaux mod\u00e8les de souris avec des mutations dans le g\u00e8ne de la souris pour les DHDD.<\/p>\n

Leur premier mod\u00e8le, signal\u00e9 en 2020 et 2023, \u00e9tait un mutant K42E \/ K42E. La terminologie K42E \/ K42E est une st\u00e9nographie g\u00e9n\u00e9tique, ce qui signifie que les deux copies du g\u00e8ne DHDDS de souris avaient une mutation \u00e0 l’acide amin\u00e9 num\u00e9ro 42, et ces mutations ont remplac\u00e9 l’acide amin\u00e9 de lysine (K) avec de l’acide glutamique (E). L’all\u00e8le K42E \/ K42E est observ\u00e9 dans la maladie de RP59 humaine.<\/p>\n

Les chercheurs UAB rapportent d\u00e9sormais deux autres mod\u00e8les de souris: un mutant T206A \/ K42E et un mutant T206A \/ T206A. T206A signifie que l’acide amin\u00e9 thr\u00e9onine (T) 206 des DHDD a \u00e9t\u00e9 remplac\u00e9 par l’alanine (A). \u00c0 12 mois, les souris T206A \/ K42E et les souris T206A \/ T206A ont montr\u00e9 des changements dans la structure et la fonction r\u00e9tiniennes similaires au mod\u00e8le de souris K42E \/ K42E, selon l’\u00e9tude publi\u00e9e dans la revue Mod\u00e8les et m\u00e9canismes de la maladie<\/i>.<\/p>\n

\u00ab\u00a0\u00c9tant donn\u00e9 que T206A \/ K42E est l’une des variantes r\u00e9pandues rapport\u00e9es chez les patients RP59, ces r\u00e9sultats nous rapprocheront de la compr\u00e9hension du m\u00e9canisme sous-jacent \u00e0 cette maladie\u00a0\u00bb, a d\u00e9clar\u00e9 Pittler, professeur au D\u00e9partement d’optom\u00e9trie et de la science de la vision de l’UAB.<\/p>\n

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Ces r\u00e9sultats indiquent que l’all\u00e8le DHDDS T206A, comme l’all\u00e8le K42E, provoque une maladie r\u00e9tinienne, probablement par le biais d’un m\u00e9canisme pathobiologique commun, et nous proposons que la base physiologique de la dysfonction r\u00e9tinienne dans RP59 implique une d\u00e9g\u00e9n\u00e9ration bipolaire et amacrine bipolaire.<\/p>\n

Les cellules bipolaires sont des interm\u00e9diaires dans les couches de la r\u00e9tine des cellules de rassemblement de lumi\u00e8re \u00e0 l’arri\u00e8re de la r\u00e9tine au nerf optique, qui envoie ensuite ces informations au cortex visuel du cerveau.<\/p>\n

Une constatation selon laquelle T206A \/ T206A provoque une maladie similaire aux mod\u00e8les T206A \/ K42E et K42E \/ K42E montre que l’all\u00e8le T206A lui-m\u00eame est pathog\u00e8ne, dit Pittler, m\u00eame si l’all\u00e8le T206A \/ T206A n’a pas \u00e9t\u00e9 vu chez l’homme.<\/p>\n

Chez l’homme, l’all\u00e8le T206A \/ K42E provoque le m\u00eame ph\u00e9notype mais est moins robuste que K42E \/ K42E.<\/p>\n

Les changements dans la structure et la fonction r\u00e9tiniennes chez les souris T206A \/ T206A et T206A \/ K42E, comme celles rapport\u00e9es plus t\u00f4t pour les souris K42E \/ K42E, ont \u00e9t\u00e9 une r\u00e9duction de l’\u00e9paisseur de la couche nucl\u00e9aire interne et de la r\u00e9duction des densit\u00e9s de cellules bipolaires et amacrines. L’\u00e9lectror\u00e9tinographie a r\u00e9v\u00e9l\u00e9 une r\u00e9duction des ondes B, mais une r\u00e9duction de l’\u00e9pargne des amplitudes des ondes A. L’\u00e9lectror\u00e9tinographie utilise une \u00e9lectrode \u00e0 la surface de l’\u0153il pour mesurer les r\u00e9ponses \u00e9lectriques des neurones r\u00e9tiniens \u00e0 un \u00e9clair de lumi\u00e8re et d\u00e9terminer quelles couches de neurones r\u00e9tiniennes sont d\u00e9fectueuses.<\/p>\n

La premi\u00e8re r\u00e9ponse \u00e9lectrique, l’onde A, refl\u00e8te la sant\u00e9 des cellules photor\u00e9cepteurs dans la r\u00e9tine externe qui d\u00e9tectent les photons. La deuxi\u00e8me r\u00e9ponse, la B-Wave, refl\u00e8te la sant\u00e9 des couches int\u00e9rieures de la r\u00e9tine, qui se trouvent en aval des cellules photor\u00e9ceptrices.<\/p>\n

<\/p><\/div>\n","protected":false},"excerpt":{"rendered":"

La d\u00e9g\u00e9n\u00e9rescence r\u00e9tinienne de la r\u00e9tinite pigmentaire est caus\u00e9e par une famille de mutations h\u00e9r\u00e9ditaires<\/p>\n","protected":false},"author":1,"featured_media":8987,"comment_status":"closed","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[86],"tags":[1175,49,1275,6471,6469,6470,6468,6472,1266],"class_list":["post-8986","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-les-maladies","tag-humain","tag-les","tag-modeles","tag-pathobiologie","tag-pigmentosa","tag-refletent","tag-retinite","tag-rp59","tag-souris","generate-columns","tablet-grid-50","mobile-grid-100","grid-parent","grid-50","resize-featured-image"],"yoast_head":"\nLes mod\u00e8les de souris de la r\u00e9tinite pigmentosa refl\u00e8tent la pathobiologie du RP59 humain - RVH-Synergie.org<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/rvh-synergie.org\/actualites\/les-modeles-de-souris-de-la-retinite-pigmentosa-refletent-la-pathobiologie-du-rp59-humain\/\" \/>\n<meta property=\"og:locale\" content=\"fr_FR\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Les mod\u00e8les de souris de la r\u00e9tinite pigmentosa refl\u00e8tent la pathobiologie du RP59 humain - 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