Prolonged recovery of retinal structure/function after gene therapy in an Rs1h-deficient mouse model of x-linked juvenile retinoschisis
- PMID: 16027044
- DOI: 10.1016/j.ymthe.2005.06.002
Prolonged recovery of retinal structure/function after gene therapy in an Rs1h-deficient mouse model of x-linked juvenile retinoschisis
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.
Similar articles
-
RS-1 Gene Delivery to an Adult Rs1h Knockout Mouse Model Restores ERG b-Wave with Reversal of the Electronegative Waveform of X-Linked Retinoschisis.Invest Ophthalmol Vis Sci. 2004 Sep;45(9):3279-85. doi: 10.1167/iovs.04-0576. Invest Ophthalmol Vis Sci. 2004. PMID: 15326152
-
Retinoschisin gene therapy and natural history in the Rs1h-KO mouse: long-term rescue from retinal degeneration.Invest Ophthalmol Vis Sci. 2007 Aug;48(8):3837-45. doi: 10.1167/iovs.07-0203. Invest Ophthalmol Vis Sci. 2007. PMID: 17652759
-
Preclinical Dose-Escalation Study of Intravitreal AAV-RS1 Gene Therapy in a Mouse Model of X-linked Retinoschisis: Dose-Dependent Expression and Improved Retinal Structure and Function.Hum Gene Ther. 2016 May;27(5):376-89. doi: 10.1089/hum.2015.142. Hum Gene Ther. 2016. PMID: 27036983 Free PMC article.
-
Of men and mice: Human X-linked retinoschisis and fidelity in mouse modeling.Prog Retin Eye Res. 2022 Mar;87:100999. doi: 10.1016/j.preteyeres.2021.100999. Epub 2021 Aug 11. Prog Retin Eye Res. 2022. PMID: 34390869 Review.
-
X-linked retinoschisis: a clinical and molecular genetic review.Surv Ophthalmol. 2004 Mar-Apr;49(2):214-30. doi: 10.1016/j.survophthal.2003.12.007. Surv Ophthalmol. 2004. PMID: 14998693 Review.
Cited by
-
Retinoschisin (RS1) interacts with negatively charged lipid bilayers in the presence of Ca2+: an atomic force microscopy study.Biochemistry. 2010 Aug 24;49(33):7023-32. doi: 10.1021/bi1007029. Biochemistry. 2010. PMID: 20677810 Free PMC article.
-
Gene Therapy in Inherited Retinal Diseases: An Update on Current State of the Art.Front Med (Lausanne). 2021 Oct 15;8:750586. doi: 10.3389/fmed.2021.750586. eCollection 2021. Front Med (Lausanne). 2021. PMID: 34722588 Free PMC article. Review.
-
Clinical and genetic findings in Hungarian patients with X-linked juvenile retinoschisis.Mol Vis. 2008;14:2321-32. Epub 2008 Dec 12. Mol Vis. 2008. PMID: 19093009 Free PMC article.
-
Retinal dystrophies and gene therapy.Eur J Pediatr. 2012 May;171(5):757-65. doi: 10.1007/s00431-011-1615-2. Epub 2011 Nov 15. Eur J Pediatr. 2012. PMID: 22080959 Review.
-
Intravitreal delivery of AAV8 retinoschisin results in cell type-specific gene expression and retinal rescue in the Rs1-KO mouse.Gene Ther. 2009 Jul;16(7):916-26. doi: 10.1038/gt.2009.61. Epub 2009 May 21. Gene Ther. 2009. PMID: 19458650 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
