Rod-derived Cone Viability Signaling for the Treatment of Inherited Retinal Degenerations

Research center

17 rue Moreau
75012 Paris
José-Alain Sahel

Institution

Inserm
Université Pierre et Marie Curie
CNRS
ED158
Université Pierre et Marie Curie

Laboratory

Phone: 01 53 46 25 48
UMR S 968
Labex Lifesenses

Mots clefs

Retinal Degeneration
Redox signaling
Gene therapy
Thioredoxin
Photoreceptors
Available to host a PhD student

publications

Delyfer MN, Aït-Ali N#, Camara H#, Clérin E#, Korobelnik JF, Sahel JA, Léveillard T#. J Vis Exp. 2013 Aug 14;(78).

AMD Gene Consortium (# Léveillard T one of thye senior authors). Nat Genet. 2013 Apr;45(4):433-9, 439e1-2.

Jaillard C, Mouret A, Niepon ML, Clérin E#, Yang Y, Lee-Rivera I, Aït-Ali N#, Millet-Puel G#, Cronin T, Sedmak T, Raffelsberger W,Kinzel B, Trembleau A, Poch O, Bennett J, Wolfrum U, Lledo PM, Sahel JA, Léveillard T#. Hum Mol Genet. 2012 May 15;21(10):2298-311.

Clérin E#, Wicker N, Mohand-Saïd S, Poch O, Sahel JA, Léveillard T#. BMC Ophthalmol. 2011 Dec 20;11:38.

Delyfer MN, Raffelsberger W, Mercier D, Korobelnik JF, Gaudric A, Charteris DG, Tadayoni R, Metge F, Caputo G, Barale PO, Ripp R, Muller JD, Poch O, Sahel JA, Léveillard T#. PLoS One. 2011;6(12):e28791.

Fields of research

Neurological and psychiatric diseases

Research Theme

The identification of one of the mechanisms leading to a vision loss in patients suffering from inherited degenerative retinal disorders reveals a novel family of signaling genes involved in the regulation of trophic interactions and response to oxidative stress. It represents a potential therapy for these currently untreatable diseases. The Rod-derived Cone Viability Factor is encoded by the Nucleoredoxin-like-1 gene and the Nxnl1-/- mouse experiences a progressive loss of photoreceptor cells. This gene encodes for a trophic protein whose role is to maintain the function and consequently the viability of cone photoreceptors. Interestingly, it also encodes by differential splicing for a second protein product that has the characteristics of thioredoxin-like enzyme and protects the photoreceptors and more specifically its interacting protein partner, the TAU protein, against oxidative damage. This novel signaling pathway potentially links environmental insults to an endogenous neuroprotective response.

Membres de l'équipe

Najate Ait-Ali
Naomie Berdugo
Frédéric Blond
Emmanuelle Clérin
Géraldine Millet-Puel
Manuela Argentini

Lab rotation

Does RdCVF metabolic signaling stimulate outer segment regrowth

Chercheur responsable: 

LEVEILLARD Thierry

Dates: 

1 September 2016 - 30 June 2017

Date limite de candidature: 

1 September 2016

Lab rotation proposal:

~ Sep-Dec 2016 ~ Jan-March 2017 ~ Apr-June 2017

Project:

In patients suffering from retinitis pigmentosa (RP), the most prevalent form of inherited retinal disease leading to untreatable blindness, cone outer segments are shortened with the progression of the disease, although cones survive even in advanced cases of RP. The mode of action of Rod-derived Cone Viability Factor (RdCVF) as revealed recently [Aït-Ali et al. Cell. 2015 May 7;161(4):817-32]  implies that the administration of RdCVF in RP  patients could not only stabilize their central vision but also restore vision by stimulating cone outer segments re-growth. The student will work on a mouse model we have developed to establish a proof of concept using gene therapy of this medically relevant phenomenon.

Address: Institut de la Vision - 17, rue Moreau 75012 PARIS

Phone number: + 33 1 53 46 25 48 ; Emailthierry.leveillard@inserm.fr

Website

Superviseur: 

Thierry LEVEILLARD