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Sci Rep. 2015 Aug 11;5:12910. doi: 10.1038/srep12910.

Human iPSC derived disease model of MERTK-associated retinitis pigmentosa.

Author information

1
CABIMER (Centro Andaluz de Biología Molecular y Medicina Regenerativa), Avda. Americo Vespucio s/n, Parque Científico y Tecnológico Cartuja, 41092, Sevilla, Spain.
2
Department of Physiology, Genetics and Microbiology, University of Alicante, Campus de San Vicente del Raspeig, 0369 Alicante, Spain.
3
1] Department of Genetics and Genomics, IIS-Fundación Jiménez Díaz, 28040 Madrid, Spain [2] Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
4
BioMediTech, University of Tampere, Biokatu 12, 33520 Tampere, Finland.
5
1] CABIMER (Centro Andaluz de Biología Molecular y Medicina Regenerativa), Avda. Americo Vespucio s/n, Parque Científico y Tecnológico Cartuja, 41092, Sevilla, Spain [2] Stem Cell therapies in Neurodegenerative diseases Lab, and National Stem Cell Bank-Valencia Node, Biomolecular and Bioinformatics Resources Platform PRB2,ISCIII, Research Center "Principe Felipe", c/ Eduardo Primo Yúfera 3, 46012, Valencia, Spain.

Abstract

Retinitis pigmentosa (RP) represents a genetically heterogeneous group of retinal dystrophies affecting mainly the rod photoreceptors and in some instances also the retinal pigment epithelium (RPE) cells of the retina. Clinical symptoms and disease progression leading to moderate to severe loss of vision are well established and despite significant progress in the identification of causative genes, the disease pathology remains unclear. Lack of this understanding has so far hindered development of effective therapies. Here we report successful generation of human induced pluripotent stem cells (iPSC) from skin fibroblasts of a patient harboring a novel Ser331Cysfs*5 mutation in the MERTK gene. The patient was diagnosed with an early onset and severe form of autosomal recessive RP (arRP). Upon differentiation of these iPSC towards RPE, patient-specific RPE cells exhibited defective phagocytosis, a characteristic phenotype of MERTK deficiency observed in human patients and animal models. Thus we have created a faithful cellular model of arRP incorporating the human genetic background which will allow us to investigate in detail the disease mechanism, explore screening of a variety of therapeutic compounds/reagents and design either combined cell and gene- based therapies or independent approaches.

PMID:
26263531
PMCID:
PMC4531787
DOI:
10.1038/srep12910
[Indexed for MEDLINE]
Free PMC Article

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