Functional cone rescue by RdCVF protein in a dominant model of retinitis pigmentosa

Autor: Serge Picaud, Emmanuelle Clérin, José-Alain Sahel, Saddek Mohand-Said, Thierry Léveillard, Ying Yang, Valérie Fontaine, Manuel Simonutti, Aude Danan
Přispěvatelé: Laboratoire de Physiopathologie Cellulaire et Moleculaire de la Retine, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service du Pr Sahel, Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Institut de la Vision, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute of Ophthalmology, University College of London [London] (UCL), Fondation Ophtalmologique Adolphe de Rothschild [Paris], This work was supported by Inserm, EVI-GENORET and Foundation Fighting Blindness (USA)., European Project: 29850,EVI-GENORET, Fondation Ophtalmologique A. de Rothschild, Marazova, Katia, Functional Genomics of the Retina in Health and Disease - EVI-GENORET - 29850 - OLD
Jazyk: angličtina
Rok vydání: 2009
Předmět:
MESH: Cell Death
genetic structures
[SDV.GEN] Life Sciences [q-bio]/Genetics
MESH: Amino Acid Sequence
MESH: Rats
Sprague-Dawley

MESH: Base Sequence
MESH: Electroretinography
Photoreceptor cell
Rats
Sprague-Dawley

Mice
Thioredoxins
0302 clinical medicine
MESH: Thioredoxins
MESH: Reverse Transcriptase Polymerase Chain Reaction
Drug Discovery
MESH: Animals
Rod cell
Genetics
0303 health sciences
Cell Death
medicine.diagnostic_test
biology
Reverse Transcriptase Polymerase Chain Reaction
MESH: Retina
MESH: Gene Expression Regulation
Cell biology
medicine.anatomical_structure
Rhodopsin
Retinal Cone Photoreceptor Cells
Molecular Medicine
Rats
Transgenic

Retinitis Pigmentosa
MESH: Rats
Molecular Sequence Data
MESH: Sequence Alignment
Retina
03 medical and health sciences
Retinitis pigmentosa
Electroretinography
medicine
Animals
Humans
Amino Acid Sequence
Molecular Biology
MESH: Mice
030304 developmental biology
Pharmacology
[SDV.GEN]Life Sciences [q-bio]/Genetics
MESH: Humans
MESH: Molecular Sequence Data
Base Sequence
Original Articles
medicine.disease
Cone cell
Rats
Transplantation
MESH: Retinal Cone Photoreceptor Cells
Gene Expression Regulation
MESH: Rats
Transgenic

030221 ophthalmology & optometry
biology.protein
MESH: Retinitis Pigmentosa
sense organs
Sequence Alignment
Zdroj: Molecular Therapy
Molecular Therapy, 2009, 17 (5), pp.787-95. ⟨10.1038/mt.2009.28⟩
Molecular Therapy, Cell Press, 2009, 17 (5), pp.787-95. ⟨10.1038/mt.2009.28⟩
ISSN: 1525-0016
1525-0024
DOI: 10.1038/mt.2009.28⟩
Popis: International audience; In retinitis pigmentosa (RP), a majority of causative mutations affect genes solely expressed in rods; however, cone degeneration inevitably follows rod cell loss. Following transplantation and in vitro studies, we demonstrated the role of photoreceptor cell paracrine interactions and identified a Rod-derived Cone Viability Factor (RdCVF), which increases cone survival. In order to establish the clinical relevance of such mechanism, we assessed the functional benefit afforded by the injection of this factor in a frequent type of rhodopsin mutation, the P23H rat. In this model of autosomal dominant RP, RdCVF expression decreases in parallel with primary rod degeneration, which is followed by cone loss. RdCVF protein injections induced an increase in cone cell number and, more important, a further increase in the corresponding electroretinogram (ERG). These results indicate that RdCVF can not only rescue cones but also preserve significantly their function. Interestingly, the higher amplitude of the functional versus the survival effect of RdCVF on cones indicates that RdCVF is acting more directly on cone function. The demonstration at the functional level of the therapeutic potential of RdCVF in the most frequent of dominant RP mutations paves the way toward the use of RdCVF for preserving central vision in many RP patients.
Databáze: OpenAIRE