Therapeutic strategy for handling inherited retinal degenerations in a gene-independent manner using rod-derived cone viability factors.
The most common hereditary retinal degeneration, retinitis pigmentosa (RP), leads to blindness by degeneration of cone photoreceptors. Meanwhile, genetic studies have shown that a significant proportion of RP genes is expressed only by rods, which raises the question of the mechanism leading to the degeneration of cones. Following the concept of sustainability factor cones, rods secrete survival factors that are necessary to maintain the cones, named Rod-derived Cone Viability Factors (RdCVFs). In patients suffering from RP, loss of rods results in the loss of RdCVFs expression and followed by cone degeneration. We have identified the bifunctional genes nucleoredoxin-like 1 and 2 that encode for, by differential splicing, a thioredoxin enzyme and a cone survival factor, respectively RdCVF and RdCVF2. The administration of these survival factors would maintain cones and central vision in most patients suffering from RP.
Inserm, U968, département de génétique, Institut de la vision, 17, rue Moreau, 75012 Paris, France; UMR_S 968, département de génétique, université Pierre-et-Marie-Curie (Paris-6), Institut de la vision, 17, rue Moreau, 75012 Paris, France; CNRS, UMR_7210, 75012 Paris, France. Electronic address: thierry.leveillard@inserm.fr.
Thierry
T
Léveillard
Inserm, U968, département de génétique, Institut de la vision, 17, rue Moreau, 75012 Paris, France; UMR_S 968, département de génétique, université Pierre-et-Marie-Curie (Paris-6), Institut de la vision, 17, rue Moreau, 75012 Paris, France; CNRS, UMR_7210, 75012 Paris, France.
Ram
R
Fridlich
Inserm, U968, département de génétique, Institut de la vision, 17, rue Moreau, 75012 Paris, France; UMR_S 968, département de génétique, université Pierre-et-Marie-Curie (Paris-6), Institut de la vision, 17, rue Moreau, 75012 Paris, France; CNRS, UMR_7210, 75012 Paris, France.
Emmanuelle
E
Clérin
Inserm, U968, département de génétique, Institut de la vision, 17, rue Moreau, 75012 Paris, France; UMR_S 968, département de génétique, université Pierre-et-Marie-Curie (Paris-6), Institut de la vision, 17, rue Moreau, 75012 Paris, France; CNRS, UMR_7210, 75012 Paris, France.
Najate
N
Aït-Ali
Inserm, U968, département de génétique, Institut de la vision, 17, rue Moreau, 75012 Paris, France; UMR_S 968, département de génétique, université Pierre-et-Marie-Curie (Paris-6), Institut de la vision, 17, rue Moreau, 75012 Paris, France; CNRS, UMR_7210, 75012 Paris, France.
Géraldine
G
Millet-Puel
Inserm, U968, département de génétique, Institut de la vision, 17, rue Moreau, 75012 Paris, France; UMR_S 968, département de génétique, université Pierre-et-Marie-Curie (Paris-6), Institut de la vision, 17, rue Moreau, 75012 Paris, France; CNRS, UMR_7210, 75012 Paris, France.
Céline
C
Jaillard
Inserm, U968, département de génétique, Institut de la vision, 17, rue Moreau, 75012 Paris, France; UMR_S 968, département de génétique, université Pierre-et-Marie-Curie (Paris-6), Institut de la vision, 17, rue Moreau, 75012 Paris, France; CNRS, UMR_7210, 75012 Paris, France.
Ying
Y
Yang
Wilmer Ophthalmological Institute, Johns Hopkins University School of Medicine, 600N. Wolfe St., Baltimore MD 21287, USA.
Donald
D
Zack
Laboratoire de spectrométrie de masse bio-organique, IPHC-DSA, ULP, CNRS, UMR7178, 23, rue du Lœss, BP28, 67037 Strasbourg cedex 2, France.
Alain
A
van-Dorsselaer
Inserm, U968, département de génétique, Institut de la vision, 17, rue Moreau, 75012 Paris, France; UMR_S 968, département de génétique, université Pierre-et-Marie-Curie (Paris-6), Institut de la vision, 17, rue Moreau, 75012 Paris, France; CNRS, UMR_7210, 75012 Paris, France.
José-Alain
JA
Sahel
D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology; D012162:Retinal Degeneration / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D017948:Retinal Rod Photoreceptor Cells / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000188:drug therapy / Q000473:pathology; D013879:Thioredoxins / Q000235:genetics* / Q000627:therapeutic use*
C488098:NXNL1 protein, human; D013879:Thioredoxins
Cone photoreceptors; Nucleoredoxin-like; Photorécepteurs à cône; Redox signalling; Signalisation redox; TAU; Thioredoxin; Thiorédoxine; Vision