Human iPSC derived disease model of MERTK-associated retinitis pigmentosa
Lukovic, Dunja; Castro, Ana Artero; Garcia Delgado, Ana Belen; de los Angeles, Maria; Bernal, Martin; Pelaez, Noelia Luna; Diez Lloret, Andrea; Espejo, Rocio Perez; Kamenarova, Kunka; Sánchez, Laura Férnandez; Cuenca, Nicolás; Cortón, Marta; Fernandez, Almudena Avila; Sorkio, Anni; Skottman, Heli; Ayuso, Carmen; Erceg, Slaven; Bhattacharya, Shomi S (2015)
Lukovic, Dunja
Castro, Ana Artero
Garcia Delgado, Ana Belen
de los Angeles, Maria
Bernal, Martin
Pelaez, Noelia Luna
Diez Lloret, Andrea
Espejo, Rocio Perez
Kamenarova, Kunka
Sánchez, Laura Férnandez
Cuenca, Nicolás
Cortón, Marta
Fernandez, Almudena Avila
Sorkio, Anni
Skottman, Heli
Ayuso, Carmen
Erceg, Slaven
Bhattacharya, Shomi S
2015
Scientific Reports 5
12910
BioMediTech - BioMediTech
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:uta-201608042132
https://urn.fi/URN:NBN:fi:uta-201608042132
Tiivistelmä
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.
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