Cohen Syndrome-Associated Cataract Is Explained by VPS13B Functions in Lens Homeostasis and Is Modified by Additional Genetic Factors
| Autor: | Romain Da Costa, Isabelle Audo, Laurence Olivier-Faivre, Serge Picaud, Laurence Duplomb, Niyazi Acar, Manuel Simonutti, Eléonore Lizé, Quénol Cesar, Christel Thauvin-Robinet, Audrey Geissler, Muhammad Ansar, Vincent Lhussiez, Emeline F. Nandrot, Elisabeth Dubus, André Bouchot, Sylvie Nguyen |
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| Přispěvatelé: | Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Bourgogne Franche-Comté [COMUE] (UBFC), University of Geneva [Switzerland], The Regional Council of Bourgogne-Franche Comté and the European Union through the Plan d'Actions Régional pour l'Innovation (PARI) and the Programme opérationnel FEDER-FSE Bourgogne 2014–2020, funds from the Fondation de France/Fondation de l'Oeil (N.A.) and funds from the JED Fondation (L.F., V.L.), funds from Fondation Maladies Rares., HAL-SU, Gestionnaire, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Genève = University of Geneva (UNIGE) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
genetic structures Developmental Disabilities Vesicular Transport Proteins 030105 genetics & heredity surgery genetic background chemistry.chemical_compound Lens Myopia Homeostasis Mice Knockout Cohen syndrome [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology medicine.diagnostic_test Retinal Degeneration Genetic disorder inflamma- tion VPS13B cataract Knockout mouse Microcephaly Muscle Hypotonia medicine.medical_specialty mouse model Blotting Western Retinitis Fingers Ophthalmoscopy 03 medical and health sciences Cataracts Intellectual Disability Ophthalmology Lens Crystalline medicine Animals Obesity business.industry fibrosis Retinal genetic modifiers medicine.disease eye diseases Mice Inbred C57BL Disease Models Animal ophthalmology 030104 developmental biology Gene Expression Regulation chemistry inflammation RNA sense organs business [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Zdroj: | Investigative Ophthalmology & Visual Science Investigative Ophthalmology & Visual Science, Association for Research in Vision and Ophthalmology, 2020, 61 (11), pp.18. ⟨10.1167/iovs.61.11.18⟩ Investigative Ophthalmology & Visual Science, 2020, 61 (11), pp.18. ⟨10.1167/iovs.61.11.18⟩ |
| ISSN: | 1552-5783 0146-0404 |
| DOI: | 10.1167/iovs.61.11.18⟩ |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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