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Identification and characterization of rod-derived cone viability factor

Nature Genetics volume 36, pages 755–759 (2004)Cite this article

Abstract

Retinitis pigmentosa is an untreatable, inherited retinal disease that leads to blindness. The disease initiates with the loss of night vision due to rod photoreceptor degeneration, followed by irreversible, progressive loss of cone photoreceptor1,2,3. Cone loss is responsible for the main visual handicap, as cones are essential for day and high-acuity vision4. Their loss is indirect, as most genes associated with retinitis pigmentosa are not expressed by these cells. We previously showed that factors secreted from rods are essential for cone viability5,6,7,8. Here we identified one such trophic factor by expression cloning and named it rod-derived cone viability factor (RdCVF). RdCVF is a truncated thioredoxin-like protein specifically expressed by photoreceptors. The identification of this protein offers new treatment possibilities for retinitis pigmentosa.

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Figure 1: Schematic representation of the expression cloning strategy.
Figure 2: Viability activity of RdCVF.
Figure 3: Expression of RdCVF mRNA.
Figure 4: Expression of RdCVF protein.
Figure 5: RdCVF localization in 35-d-old wild-type mouse retina.

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Acknowledgements

We thank A. Gluck, J. Ravey, D. Thiersé, M. Simonutti, V. Forster, N. Hanotteau, G. Millet-Puel, G. Lucchi, P. Oberlin and G. Tarlet for technical assistance; A. Dolemeyer, C. Grolleau, E. Scherbeck and P.-Y. Boelle for help; P. Chambon for support; and E. Borelli, O. Goureau, V. Heidinger, A. Triller and D. Zack for critical reading of the manuscript. This work was financed by Novartis, Inserm, Ministère de la Recherche, the Association Française contre les Myopathies, the Fédération des Aveugles de France, Retina France, Foundation Fighting Blindness (USA), IPSEN Foundation and the European Community (PRO-AGE-RET program).

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Author notes

  1. Thierry Léveillard and José-Alain Sahel: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratoire de Physiopathologie Cellulaire et Moléculaire et de la Rétine, Inserm U592, Université Pierre et Marie Curie, Hôpital St-Antoine, 184 rue du Faubourg St-Antoine, Paris, 75571 cedex 12, France

    Thierry Léveillard, Saddek Mohand-Saïd, Olivier Lorentz, David Hicks, Anne-Claire Fintz, Emmanuelle Clérin, Manuel Simonutti, Valérie Forster, Nükhet Cavusoglu & José-Alain Sahel

  2. Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 rue Laurent Fries, Illkirch, 67404, France

    Frédéric Chalmel, Pascal Dollé & Olivier Poch

  3. Novartis Pharma AG Ophthalmology Research WKL-127.1.04, Basel, CH-4002, Switzerland

    George Lambrou

  4. Institute of Ophthalmology, University College of London, UK

    José-Alain Sahel

Authors
  1. Thierry Léveillard
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Corresponding author

Correspondence to Thierry Léveillard.

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Competing interests

The authors filed a patent on disease-associated protein on 4 June 2001 (international extension on 4 June 2002), EP 1379657.

Supplementary information

Supplementary Fig. 1

RdCVF sequence. (PDF 82 kb)

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Léveillard, T., Mohand-Saïd, S., Lorentz, O. et al. Identification and characterization of rod-derived cone viability factor. Nat Genet 36, 755–759 (2004). https://doi.org/10.1038/ng1386

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