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 |
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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 |
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