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

Tasneem P Sharma; Luke A Wiley; S. Scott Whitmore; Kristin R Anfinson; Cathryn M Cranston; Douglas J Oppedal; Heather T Daggett; Robert F Mullins; Budd A Tucker; Edwin M Stone

doi:10.1016/j.scr.2017.03.005

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

Journal article

Open access

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

Tasneem P Sharma, Luke A Wiley, S. Scott Whitmore, Kristin R Anfinson, Cathryn M Cranston, Douglas J Oppedal, Heather T Daggett, Robert F Mullins, Budd A Tucker and Edwin M Stone

Stem Cell Research, Vol.21(C), pp.58-70

05/2017

DOI: 10.1016/j.scr.2017.03.005

PMID: 28390992

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Abstract

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. •Utilizing patient-derived iPSCs to study RP.•Generating iPSC-derived retinal organoids from patients with molecularly confirmed TRNT1-associated RP.•Mutations in TRNT1 disrupt autophagy in patient-specific retinal cells.

Retinal organoids

Oxidative stress

TRNT 1

Induced pluripotent stem cells

Retinitis pigmentosa

Autophagy

Details

Title: Subtitle: Patient-specific induced pluripotent stem cells to evaluate the pathophysiology of TRNT1-associated Retinitis pigmentosa
Creators: Tasneem P Sharma
Luke A Wiley
S. Scott Whitmore
Kristin R Anfinson
Cathryn M Cranston
Douglas J Oppedal
Heather T Daggett
Robert F Mullins
Budd A Tucker
Edwin M Stone
Resource Type: Journal article
Publication Details: Stem Cell Research, Vol.21(C), pp.58-70
DOI: 10.1016/j.scr.2017.03.005
PMID: 28390992
NLM abbreviation: Stem Cell Res
ISSN: 1873-5061
eISSN: 1876-7753
Publisher: Elsevier B.V
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: EY026008-02
Language: English
Date published: 05/2017
Academic Unit: The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9983980054102771

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