| First Author | Pang JJ | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 4 | Pages | e35250 |
| PubMed ID | 22509403 | Mgi Jnum | J:187090 |
| Mgi Id | MGI:5435345 | Doi | 10.1371/journal.pone.0035250 |
| Citation | Pang JJ, et al. (2012) AAV-mediated cone rescue in a naturally occurring mouse model of CNGA3-achromatopsia. PLoS One 7(4):e35250 |
| abstractText | 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. |
