Achromatopsia as a potential candidate for gene therapy.
Achromatopsia is an autosomal recessive retinal disease involving loss of cone function that afflicts approximately 1 in 30,000 individuals. Patients with achromatopsia usually have visual acuities lower than 20/200 because of the central vision loss, photophobia, complete color blindness and reduced cone-mediated electroretinographic (ERG) amplitudes. Mutations in three genes have been found to be the primary causes of achromatopsia, including CNGB3 (beta subunit of the cone cyclic nucleotide-gated cation channel), CNGA3 (alpha subunit of the cone cyclic nucleotide-gated cation channel), and GNAT2 (cone specific alpha subunit of transducin). Naturally occurring mouse models with mutations in Cnga3 (cpfl5 mice) and Gnat2 (cpfl3 mice) were discovered at The Jackson Laboratory. A natural occurring canine model with CNGB3 mutations has also been found. These animal models have many of the central phenotypic features of the corresponding human diseases. Using adeno-associated virus (AAV)-mediated gene therapy, we and others show that cone function can be restored in all three models. These data suggest that human achromatopsia may be a good candidate for corrective gene therapy.
Department of Ophthalmology, University of Florida, Gainesville, FL 32610, USA. jpang@ufl.edu
Ji-Jing
JJ
Pang
John
J
Alexander
Bo
B
Lei
Wentao
W
Deng
Keqing
K
Zhang
Qiuhong
Q
Li
Bo
B
Chang
William W
WW
Hauswirth
D000818:Animals; D003117:Color Vision Defects / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics / Q000627:therapeutic use; D004285:Dogs; D015316:Genetic Therapy; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D009154:Mutation / Q000235:genetics
D054815:Cyclic Nucleotide-Gated Cation Channels; C515337:Gnat2 protein, mouse; D020962:Heterotrimeric GTP-Binding Proteins