Molecular Genetics and Genomics

, Volume 288, Issue 10, pp 459–467

Gene replacement therapy for retinal CNG channelopathies

  • Christian Schön
  • Martin Biel
  • Stylianos Michalakis
Review

DOI: 10.1007/s00438-013-0766-4

Cite this article as:
Schön, C., Biel, M. & Michalakis, S. Mol Genet Genomics (2013) 288: 459. doi:10.1007/s00438-013-0766-4

Abstract

Visual phototransduction relies on the function of cyclic nucleotide-gated channels in the rod and cone photoreceptor outer segment plasma membranes. The role of these ion channels is to translate light-triggered changes in the second messenger cyclic guanosine 3′–5′-monophosphate levels into an electrical signal that is further processed within the retinal network and then sent to higher visual centers. Rod and cone photoreceptors express distinct CNG channels. The rod photoreceptor CNG channel is composed of one CNGB1 and three CNGA1 subunits, whereas the cone channel is formed by one CNGB3 and three CNGA3 subunits. Mutations in any of these channel subunits result in severe and currently untreatable retinal degenerative diseases like retinitis pigmentosa or achromatopsia. In this review, we provide an overview of the human diseases and relevant animal models of CNG channelopathies. Furthermore, we summarize recent results from preclinical gene therapy studies using adeno-associated viral vectors and discuss the efficacy and translational potential of these gene therapeutic approaches.

Keywords

Adeno-associated virusCNG channelCyclic nucleotide-gated channelChannelopathiesGene therapyRetina

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Christian Schön
    • 1
  • Martin Biel
    • 1
  • Stylianos Michalakis
    • 1
  1. 1.Center for Integrated Protein Science Munich, CIPSM and Department of Pharmacy – Center for Drug ResearchLudwig-Maximilians-Universität MünchenMunichGermany