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Long-term expression of melanopsin and channelrhodopsin causes no gross alterations in the dystrophic dog retina

Gene Therapy volume 24, pages 735–741 (2017)Cite this article

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Abstract

Several preclinical studies have investigated the potential of algal channelrhodopsin and human melanopsin as optogenetic tools for vision restoration. In the present study, we assessed the potentially deleterious effects of long-term expression of these optogenes on the diseased retina in a large animal model of retinal degeneration, the RPE65-deficient Briard dog model of Leber congenital amaurosis. Intravitreal injection of adeno-associated virus vectors expressing channelrhodopsin and melanopsin had no effect on retinal thickness over a 16-month period post injection. Our data support the safety of the optogenetic approach for the treatment of blindness.

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Acknowledgements

We thank the Vector Core Facility for producing the rAAV vectors and the staff of the Boisbonne Center for animal care. We also thank Philippe Hulin and Steven Nedellec (Cellular and Tissular Imaging Core Facility, INSERM, Nantes, France) for their technical assistance. This work was supported by unrestricted grants from the Association Française Contre les Myopathies, INSERM, the Fondation Pour la Thérapie Génique en Pays de la Loire and the Region Pays de la Loire. SP was supported for this work by the Institut National de la Santé et de la Recherche Médicale (INSERM), Pierre et Marie Curie University (UPMC), the Centre National de la Recherche Scientifique (CNRS), FRM (Fondation pour la Recherche Médicale), the E-Rare Project (OPTOREMODE), the Foundation Fighting Blindness (Wynn-Gund translational research award), the French State program ‘Investissements d'Avenir’ managed by the Agence Nationale de la Recherche (LIFESENSES: ANR-10-LABX-65) and by the French Agence National pour la Recherche (ANR) as part of the second Investissements d’Avenir program (ANR-15-RHUS-0001).

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Author notes

  1. B Ameline and K-T Tshilenge: These authors contributed equally to this work.

Authors and Affiliations

  1. Atlantic Gene Therapies, INSERM UMR 1089, Université de Nantes, CHU de Nantes, Nantes, France

    B Ameline, K-T Tshilenge, M Biget, L Libeau, A Mendes-Madeira, N Provost, C Guihal, P Moullier, V Pichard, T Cronin & C Isiegas

  2. CHU de Nantes, Service d’Ophtalmologie, Nantes, France

    M Weber & L Libeau

  3. INSERM, U968, Paris, France

    R Caplette & S Picaud

  4. Sorbonne Universités, UPMC Université de Paris 06, UMR_S 968, Institut de la Vision, Paris, France

    R Caplette & S Picaud

  5. CNRS, UMR_7210, Paris, France

    R Caplette & S Picaud

Authors
  1. B Ameline
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  2. K-T Tshilenge
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  3. M Weber
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  7. A Mendes-Madeira
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  13. T Cronin
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Corresponding author

Correspondence to C Isiegas.

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Competing interests

Serge Picaud is a stakeholder in the company Gensight Biologics. All other co-authors declare no conflict of interest.

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Supplementary Information accompanies this paper on Gene Therapy website

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Ameline, B., Tshilenge, KT., Weber, M. et al. Long-term expression of melanopsin and channelrhodopsin causes no gross alterations in the dystrophic dog retina. Gene Ther 24, 735–741 (2017). https://doi.org/10.1038/gt.2017.63

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