Molecular Therapy
Volume 12, Issue 4, October 2005, Pages 644-651
Journal home page for Molecular Therapy

Article
Prolonged Recovery of Retinal Structure/Function after Gene Therapy in an Rs1h-Deficient Mouse Model of X-Linked Juvenile Retinoschisis

https://doi.org/10.1016/j.ymthe.2005.06.002Get rights and content
Under a Creative Commons license
open archive

Abstract

X-linked juvenile retinoschisis (RS) is a common cause of juvenile macular degeneration in males. RS is characterized by cystic spoke-wheel-like maculopathy, peripheral schisis, and a negative (b-wave more reduced than a-wave) electroretinogram (ERG). These symptoms are due to mutations in the RS1 gene in Xp22.2 leading to loss of functional protein. No medical treatment is currently available. We show here that in an Rs1h-deficient mouse model of human RS, delivery of the human RS1 cDNA with an AAV vector restored expression of retinoschisin to both photoreceptors and the inner retina essentially identical to that seen in wild-type mice. More importantly, unlike an earlier study with a different AAV vector and promoter, this work shows for the first time that therapeutic gene delivery using a highly specific AAV5–opsin promoter vector leads to progressive and significant improvement in both retinal function (ERG) and morphology, with preservation of photoreceptor cells that, without treatment, progressively degenerate.

Keywords

retinoschisis
knockout mouse
gene therapy
AAV vector
electroretinogram
opsin promoter

Cited by (0)