Transgenic Expression of Cacna1f Rescues Vision and Retinal Morphology in a Mouse Model of Congenital Stationary Night Blindness 2A (CSNB2A)
| Autor: | N. Torben Bech-Hansen, Robert L. Chow, Amy S. Lee, Lisa Nguyen, Kenichi Ito, Derek Waldner, Li-Li Chen, William K. Stell, Derrick E. Rancourt, François Tremblay |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Retinal Disorder genetic structures Calcium Channels L-Type Cacna1f Biomedical Engineering Mice Transgenic Biology Article Retina 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Night Blindness calcium channels Retinitis pigmentosa medicine Myopia Animals CSNB2A Congenital stationary night blindness medicine.diagnostic_test Retinal Eye Diseases Hereditary Genetic Diseases X-Linked Macular degeneration medicine.disease channelopathies eye diseases Ophthalmology Cav1.4 030104 developmental biology medicine.anatomical_structure chemistry 030221 ophthalmology & optometry sense organs Neuroscience Electroretinography |
| Zdroj: | Translational Vision Science & Technology |
| ISSN: | 2164-2591 |
| Popis: | Purpose Congenital stationary night blindness 2A (CSNB2A) is a genetic retinal disorder characterized by poor visual acuity, nystagmus, strabismus, and other signs of retinal dysfunction resulting from mutations in Cacna1f -the gene coding for the pore-forming subunit of the calcium channel CaV1.4. Mouse models of CSNB2A have shown that mutations causing the disease deleteriously affect photoreceptors and their synapses with second-order neurons. This study was undertaken to evaluate whether transgenic expression of Cacna1f could rescue morphology and visual function in a Cacna1f-KO model of CSNB2A. Methods Strategic creation, breeding and use of transgenic mouse lines allowed for Cre-driven retina-specific expression of Cacna1f in a CSNB2A model. Transgene expression and retinal morphology were investigated with immunohistochemistry in retinal wholemounts or cross-sections. Visual function was assessed by optokinetic response (OKR) analysis and electroretinography (ERG). Results Mosaic, prenatal expression of Cacna1f in the otherwise Cacna1f-KO retina was sufficient to rescue some visual function. Immunohistochemical analyses demonstrated wild-type-like photoreceptor and synaptic morphology in sections with transgenic expression of Cacna1f. Conclusions This report describes a novel system for Cre-inducible expression of Cacna1f in a Cacna1f-KO mouse model of CSNB2A and provides preclinical evidence for the potential use of gene therapy in the treatment of CSNB2A. Translational relevance These data have relevance in the treatment of CSNB2A and in understanding how photoreceptor integration might be achieved in retinas in which photoreceptors have been lost, such as retinitis pigmentosa, age-related macular degeneration, and other degenerative conditions. |
| Databáze: | OpenAIRE |
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