aav-mediated cone rescue in a naturally occurring mouse model of cnga3-achromatopsiaaav-mediated锥救援cnga3-achromatopsia的自然发生的小鼠模型.pdfVIP

AAV-Mediated Cone Rescue in a Naturally Occurring Mouse Model of CNGA3-Achromatopsia 1,2 . 1. 1,2 3 4 4 1 Ji-jing Pang * , Wen-Tao Deng , Xufeng Dai , Bo Lei , Drew Everhart , Yumiko Umino , Jie Li , 3 1 1 1 1 1 1 1 Keqing Zhang , Song Mao , Sanford L. Boye , Li Liu , Vince A. Chiodo , Xuan Liu , Wei Shi , Ye Tao , Bo Chang5, William W. Hauswirth1 1 Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida, United States of America, 2 Eye Hospital, School of Optometry and Ophthalmology, Wenzhou Medical College, Wenzhou, China, 3 Chongqing Key Laboratory of Ophthalmology, Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China, 4 Ophthalmology, SUNY Upstate Medical University, Syracuse, New York, United States of America, 5 The Jackson Laboratory, Bar Harbor, Maine, United States of America 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 sensiti