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Cyclic nucleotide-gated cation channel beta-3 (Cone photoreceptor cGMP-gated channel subunit beta) (Cyclic nucleotide-gated cation channel modulatory subunit) (Cyclic nucleotide-gated channel beta-3) (CNG channel beta-3)


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

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.

MeSH Terms

  • Aging
  • Animals
  • Arrestins
  • Cell Survival
  • Color Vision Defects
  • Cyclic Nucleotide-Gated Cation Channels
  • Disease Models, Animal
  • Gene Transfer Techniques
  • Genetic Therapy
  • Genetic Vectors
  • Humans
  • Injections
  • Mice
  • Mice, Transgenic
  • Opsins
  • Organ Specificity
  • Promoter Regions, Genetic
  • Protein Transport
  • Retina
  • Retinal Cone Photoreceptor Cells
  • Time Factors
  • Vision, Ocular
  • Visual Acuity