RGD Reference Report - Long-term and age-dependent restoration of visual function in a mouse model of CNGB3-associated achromatopsia following gene therapy. - Rat Genome Database

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Long-term and age-dependent restoration of visual function in a mouse model of CNGB3-associated achromatopsia following gene therapy.

Authors: Carvalho, LS  Xu, J  Pearson, RA  Smith, AJ  Bainbridge, JW  Morris, LM  Fliesler, SJ  Ding, XQ  Ali, RR 
Citation: Carvalho LS, etal., Hum Mol Genet. 2011 Aug 15;20(16):3161-75. doi: 10.1093/hmg/ddr218. Epub 2011 May 15.
RGD ID: 9068450
Pubmed: (View Article at PubMed) PMID:21576125
DOI: Full-text: DOI:10.1093/hmg/ddr218

Mutations in the CNGB3 gene account for >50% of all known cases of achromatopsia. Although of early onset, its stationary character and the potential for rapid assessment of restoration of retinal function following therapy renders achromatopsia a very attractive candidate for gene therapy. Here we tested the efficacy of an rAAV2/8 vector containing a human cone arrestin promoter and a human CNGB3 cDNA in CNGB3 deficient mice. Following subretinal delivery of the vector, CNGB3 was detected in both M- and S-cones and resulted in increased levels of CNGA3, increased cone density and survival, improved cone outer segment structure and normal subcellular compartmentalization of cone opsins. Therapy also resulted in long-term improvement of retinal function, with restoration of cone ERG amplitudes of up to 90% of wild-type and a significant improvement in visual acuity. Remarkably, successful restoration of cone function was observed even when treatment was initiated at 6 months of age; however, restoration of normal visual acuity was only possible in younger animals (e.g. 2-4 weeks old). This study represents achievement of the most substantial restoration of visual function reported to date in an animal model of achromatopsia using a human gene construct, which has the potential to be utilized in clinical trials.



Disease Annotations    
Achromatopsia 1  (IMP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Cngb3  (cyclic nucleotide gated channel subunit beta 3)

Genes (Mus musculus)
Cngb3  (cyclic nucleotide gated channel beta 3)

Genes (Homo sapiens)
CNGB3  (cyclic nucleotide gated channel subunit beta 3)


Additional Information