1.4. Thérapie génique des dystrophies rétiniennes

The retina is particularly amenable to gene therapy because it is accessible via relatively non-invasive routes, it is small and enclosed allowing the use of small vector doses, and it is immuno-privileged due to sequestration from the systemic circulation by the blood-retina barrier.

Moreover, inherited retinal dystrophies (IRDs) are favourable candidates for gene therapy because they are often monogenic, have characteristic clinical signs allowing an early diagnosis, and progress slowly to blindness allowing a large therapeutic window.

iPSc petitThe aim of our work is to find a viable alternative to palliate this lack of animal models. One way would be to perform preclinical studies on human cellular models of the diseased retina. The caveat is that it is impossible to obtain retinal cells directly from a patient.Therefore, our work is aimed at generating these cells via the intermediate of an innovative and powerful tool, induced pluripotent stem cells (iPSc).

VK RPEWe have generated iPSc-derived RPE for two different IRDs: choroideremia and retinitis punctata albescens. The iPSc-derived RPE is morphologically and functionally characteristic of the tissue in vivo. It is a polarized, pigmented cobblestone that is capable of fluid transport, phagocytosis, visual cycle kinetics and growth factor secretion. Moreover it reproduces the biochemical defect of patients, therefore Therefore, the iPSc-derived RPE is a powerful tool for screening the efficiency of novel therapeutics.


VK Bestrophin LRATBy transducing this epithelium with a viral vector carrying a healthy copy of the causative gene, we can obtain the proof of concept for a restoration of a normal phenotype, a first step towards clinical translation. Similarly, the generated RPE can be used to screen the efficiency of gene editing tools or novel pharmacological agents. Finally, such a model generated in vitro represents a first step towards cell therapy approaches.


Major publications

Torriano S., et al., Hum Mol Genet, doi:10.1093/hmg/ddx244, 2017
Cereso N., et al.,  Mol Ther Methods Clin Dev, 1: 14011, 2014
Hippert C., et al., PLoS One, 7(4): e35318, 2012
Maurice T., et al., Neurobiol Aging, 30:987-1000, 2009
Hippert C., et al., Mol Ther, 16: 1372-1381, 2008
Kalatzis V., et al., Hum Mol Genet, 20:5940-5949, 2001
Kalatzis V., et al., EMBO J, 13: 1361-1371, 2004
Kalatzis V., et al., Nature Genet, 15: 157-164, 1997


  • Pr Ian MacDonald, Alberta University, Edmonton, Canada
  • Dr. Yvan Arsenijevic, University of Lausanne, Switzerland
  • Pr Carmen Ayuso, Fundacion Jimenez Diaz, Madrid, Spain
  • Dr. Mariya Moosajee, University College London, UK
  • Dr Anne-Françoise Roux, CHRU Montpellier, France
  • Pr. Franck Pellestor, CHRU, Montpellier, France
  • Pr. John De Vos, IRB, Montpellier, France
  • Dr Sara Salinas, Inserm, Montpellier, France
  • Dr. Florence Cammas, IRCM, Montpellier, France

Fundings sources

VK sponsors 2




Viki Kalatzis