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. 2010 Apr 7;2(26):26ps16.
doi: 10.1126/scitranslmed.3000866.

Rod-derived cone viability factor for treating blinding diseases: from clinic to redox signaling

Thierry Léveillard  1 , José-Alain Sahel
Affiliations

Rod-derived cone viability factor for treating blinding diseases: from clinic to redox signaling

Thierry Léveillard et al. Sci Transl Med. .

Abstract

The identification of one mechanism that causes vision loss in inherited degenerative retinal disorders revealed a new signaling molecule that represents a potential therapy for these currently untreatable diseases. This protein, called rod-derived cone viability factor (RdCVF), maintains the function and consequently the viability of cone photoreceptor cells in the retina; mice that lack this factor exhibit a progressive loss of photoreceptor cells. The gene encoding RdCVF also encodes, by differential splicing, a second product that has characteristics of a thioredoxin-like enzyme and protects both photoreceptor cells and, more specifically, its interacting protein partner, the tau protein, against oxidative damage. This signaling pathway potentially links environmental insults to an endogenous neuroprotective response.

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Conflict of interest statement

Conflicts of interest: T.L. and J-A.S. are patent-holders on the use of RdCVF and RdCVF2 for the treatment of retinal and neurological disease

Figures

Fig. 1
Fig. 1. Organization of the retina
CREDIT: C. BICKEL/SCIENCE TRANSLATIONAL MEDICINE
Fig. 2
Fig. 2. Schematic representation of the Nxnl1 gene and its two products, RdCVF and RdCVFL
Alternative splicing generates the truncated trophic factor and the longer thioredoxin-like enzyme. In the ribbon diagrams, the thioredoxin catalytic site is shown in yellow, the shared portion of the thioredoxin fold in red, the additional thioredoxin fold (found only in RdCVFL) in green, and the RdCVF specific loops in blue. CREDIT: C. BICKEL/SCIENCE TRANSLATIONAL MEDICINE
Fig. 3
Fig. 3. Maintenance of the cone outer segment by RdCVF
RdCVF was injected into eyes of the P23H rat, a model of autosomal dominant RP. The cone cells (green) of the RdCVF-injected animal (bottom panel) display a longer outer segment (indicated by double arrows) and smaller diameter (asterisk) than those in the vehicle-injected rat (top panel). The relative positions of the cone outer segment in each case are indicated on the diagram on the right.
See this image and copyright information in PMC

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