Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

Cohen Syndrome-Associated Cataract Is Explained by VPS13B Functions in Lens Homeostasis and Is Modified by Additional Genetic Factors

Abstract : Purpose: Cohen syndrome (CS) is a rare genetic disorder caused by variants of the VPS13B gene. CS patients are affected with a severe form of retinal dystrophy, and in several cases cataracts also develop. The purpose of this study was to investigate the mechanisms and risk factors for cataract in CS, as well as to report on cataract surgeries in CS patients. Methods: To understand how VPS13B is associated with visual impairments in CS, we generated the Vps13b∆Ex3/∆Ex3 mouse model. Mice from 1 to 3 months of age were followed by ophthalmoscopy and slit-lamp examinations. Phenotypes were investigated by histology, immunohistochemistry, and western blot. Literature analysis was performed to determine specific characteristic features of cataract in CS and to identify potential genotype–phenotype correlations. Results: Cataracts rapidly developed in 2-month-old knockout mice and were present in almost all lenses at 3 months. Eye fundi appeared normal until cataract development. Lens immunostaining revealed that cataract formation was associated with the appearance of large vacuoles in the cortical area, epithelial–mesenchymal transition, and fibrosis. In later stages, cataracts became hypermature, leading to profound retinal remodeling due to inflammatory events. Literature analysis showed that CS-related cataracts display specific features compared to other forms of retinitis pigmentosa-related cataracts, and their onset is modified by additional genetic factors. Corroboratively, we were able to isolate a subline of the Vps13b∆Ex3/∆Ex3 model with delayed cataract onset. Conclusions: VPS13B participates in lens homeostasis, and the CS-related cataract development dynamic is linked to additional genetic factors.
Type de document :
Article dans une revue
Liste complète des métadonnées

Littérature citée [49 références]  Voir  Masquer  Télécharger
Contributeur : Gestionnaire Hal-Su <>
Soumis le : vendredi 16 octobre 2020 - 18:32:47
Dernière modification le : mardi 12 janvier 2021 - 11:08:39


Publication financée par une institution


Distributed under a Creative Commons Paternité - Pas d'utilisation commerciale - Pas de modification 4.0 International License



Vincent Lhussiez, Elisabeth Dubus, Quénol Cesar, Niyazi Acar, Emeline Nandrot, et al.. Cohen Syndrome-Associated Cataract Is Explained by VPS13B Functions in Lens Homeostasis and Is Modified by Additional Genetic Factors. Investigative Opthalmology & Visual Science, Association for Research in Vision and Ophthalmology (ARVO), 2020, 61 (11), pp.18. ⟨10.1167/iovs.61.11.18⟩. ⟨hal-02969762⟩



Consultations de la notice


Téléchargements de fichiers