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


CONCLUSIONS
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.
Chalmel
Frédéric
F
Division of Bioinformatics, Swiss Institute of Bioinformatics, University of Basel, CH-4056 Basel, Switzerland. frederic.chalmel@unibas.ch
Léveillard
Thierry
T
Jaillard
Céline
C
Lardenois
Aurélie
A
Berdugo
Naomi
N
Morel
Emmanuelle
E
Koehl
Patrice
P
Lambrou
George
G
Holmgren
Arne
A
Sahel
José A
JA
Poch
Olivier
O
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D002642:Chick Embryo; D003198:Computer Simulation; D017077:Culture Media, Conditioned / Q000737:chemistry; D005136:Eye Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism; D010802:Phylogeny; D020033:Protein Isoforms / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000378:metabolism*; D012174:Retinitis Pigmentosa / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D013879:Thioredoxins / Q000737:chemistry* / Q000494:pharmacology
D017077:Culture Media, Conditioned; D005136:Eye Proteins; D020033:Protein Isoforms; C525119:RdCVF protein, mouse; D013879:Thioredoxins