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Open Access Research article

Rod-derived Cone Viability Factor-2 is a novel bifunctional-thioredoxin-like protein with therapeutic potential

Frédéric Chalmel1, Thierry Léveillard2*, Céline Jaillard2, Aurélie Lardenois3, Naomi Berdugo28, Emmanuelle Morel2, Patrice Koehl4, George Lambrou5, Arne Holmgren6, José A Sahel27 and Olivier Poch3

Author Affiliations

1 Divisions of Bioinformatics and Biochemistry, Swiss Institute of Bioinformatics, University of Basel, CH-4056 Basel, Switzerland

2 Laboratoire de Physiopathologie Cellulaire et Moléculaire de la Rétine, Inserm U592, Université Pierre et Marie Curie, 75571 Paris, France

3 Laboratoire de Biologie et Génomique Structurales, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP 163, 67404 Illkirch cedex, France

4 Department of Computer Science, Genome Center, University of California, Davis, CA 95616, USA

5 Novartis Institutes for Biomedical Research, Basel 4002, Switzerland

6 Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden

7 Institute of Ophthalmology, University College of London, UK

8 Fovea-Pharmaceuticals – 12 rue Jean Antoine Le Baif – 75013 Paris

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BMC Molecular Biology 2007, 8:74  doi:10.1186/1471-2199-8-74

Published: 31 August 2007

Abstract

Background

Cone degeneration is the hallmark of the inherited retinal disease retinitis pigmentosa. We have previously identified a trophic factor "Rod-derived Cone Viability Factor (RdCVF) that is secreted by rods and promote cone viability in a mouse model of the disease.

Results

Here we report the bioinformatic identification and the experimental analysis of RdCVF2, a second trophic factor belonging to the Rod-derived Cone Viability Factor family. The mouse RdCVF gene is known to be bifunctional, encoding both a long thioredoxin-like isoform (RdCVF-L) and a short isoform with trophic cone photoreceptor viability activity (RdCVF-S). RdCVF2 shares many similarities with RdCVF in terms of gene structure, expression in a rod-dependent manner and protein 3D structure. Furthermore, like RdCVF, the RdCVF2 short isoform exhibits cone rescue activity that is independent of its putative thiol-oxydoreductase activity.

Conclusion

Taken together, these findings define a new family of bifunctional genes which are: expressed in vertebrate retina, encode trophic cone viability factors, and have major therapeutic potential for human retinal neurodegenerative diseases such as retinitis pigmentosa.