AAV-mediated cone rescue in a naturally occurring mouse model of CNGA3-achromatopsia.
Document Type
Article
Publication Date
2012
JAX Source
PLoS One 2012; 7(4):e35250.
PMID
22509403
Volume
7
Issue
4
First Page
35250
Last Page
35250
ISSN
1932-6203
Abstract
Achromatopsia is a rare autosomal recessive disorder which shows color blindness, severely impaired visual acuity, and extreme sensitivity to bright light. Mutations in the alpha subunits of the cone cyclic nucleotide-gated channels (CNGA3) are responsible for about 1/4 of achromatopsia in the U.S. and Europe. Here, we test whether gene replacement therapy using an AAV5 vector could restore cone-mediated function and arrest cone degeneration in the cpfl5 mouse, a naturally occurring mouse model of achromatopsia with a CNGA3 mutation. We show that gene therapy leads to significant rescue of cone-mediated ERGs, normal visual acuities and contrast sensitivities. Normal expression and outer segment localization of both M- and S-opsins were maintained in treated retinas. The therapeutic effect of treatment lasted for at least 5 months post-injection. This study is the first demonstration of substantial, relatively long-term restoration of cone-mediated light responsiveness and visual behavior in a naturally occurring mouse model of CNGA3 achromatopsia. The results provide the foundation for development of an AAV5-based gene therapy trial for human CNGA3 achromatopsia.
Recommended Citation
Pang J,
Deng W,
Dai X,
Lei B,
Everhart D,
Umino Y,
Li J,
Zhang K,
Mao S,
Boye S,
Liu L,
Chiodo V,
Liu X,
Shi W,
Tao Y,
Chang B,
Hauswirth W.
AAV-mediated cone rescue in a naturally occurring mouse model of CNGA3-achromatopsia. PLoS One 2012; 7(4):e35250.