[HTML][HTML] AAV-mediated cone rescue in a naturally occurring mouse model of CNGA3-achromatopsia

J Pang, WT Deng, X Dai, B Lei, D Everhart, Y Umino… - PloS one, 2012 - journals.plos.org
J Pang, WT Deng, X Dai, B Lei, D Everhart, Y Umino, J Li, K Zhang, S Mao, SL Boye, L Liu…
PloS one, 2012journals.plos.org
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 US 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 …
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.
PLOS