Patient-specific induced pluripotent stem cells to evaluate the pathophysiology of TRNT1-associated Retinitis pigmentosa.

Autor:	Sharma TP; Stephen A Wynn Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. Electronic address: tasneem-sharma@uiowa.edu., Wiley LA; Stephen A Wynn Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. Electronic address: luke-wiley@uiowa.edu., Whitmore SS; Stephen A Wynn Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. Electronic address: steven-whitmore@uiowa.edu., Anfinson KR; Stephen A Wynn Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. Electronic address: kristin-anfinson@uiowa.edu., Cranston CM; Stephen A Wynn Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. Electronic address: cathryn-cranston@uiowa.edu., Oppedal DJ; Stephen A Wynn Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. Electronic address: douglas-oppedal@uiowa.edu., Daggett HT; Stephen A Wynn Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. Electronic address: heather-daggett@uiowa.edu., Mullins RF; Stephen A Wynn Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. Electronic address: robert-mullins@uiowa.edu., Tucker BA; Stephen A Wynn Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. Electronic address: budd-tucker@uiowa.edu., Stone EM; Stephen A Wynn Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. Electronic address: edwin-stone@uiowa.edu.
Jazyk:	angličtina
Zdroj:	Stem cell research [Stem Cell Res] 2017 May; Vol. 21, pp. 58-70. Date of Electronic Publication: 2017 Mar 18.
DOI:	10.1016/j.scr.2017.03.005
Abstrakt:	Retinitis pigmentosa (RP) is a heterogeneous group of monogenic disorders characterized by progressive death of the light-sensing photoreceptor cells of the outer neural retina. We recently identified novel hypomorphic mutations in the tRNA Nucleotidyl Transferase, CCA-Adding 1 (TRNT1) gene that cause early-onset RP. To model this disease in vitro, we generated patient-specific iPSCs and iPSC-derived retinal organoids from dermal fibroblasts of patients with molecularly confirmed TRNT1-associated RP. Pluripotency was confirmed using rt-PCR, immunocytochemistry, and a TaqMan Scorecard Assay. Mutations in TRNT1 caused reduced levels of full-length TRNT1 protein and expression of a truncated smaller protein in both patient-specific iPSCs and iPSC-derived retinal organoids. Patient-specific iPSCs and iPSC-derived retinal organoids exhibited a deficit in autophagy, as evidenced by aberrant accumulation of LC3-II and elevated levels of oxidative stress. Autologous stem cell-based disease modeling will provide a platform for testing multiple avenues of treatment in patients suffering from TRNT1-associated RP. (Copyright © 2017. Published by Elsevier B.V.)
Databáze:	MEDLINE
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