Mitochondrial replacement in an iPSC model of Leber's hereditary optic neuropathy

Raymond C B Wong; Shiang Y Lim; Sandy S C Hung; Stacey Jackson; Shahnaz Khan; Nicole J Van Bergen; Elisabeth De Smit; Helena H Liang; Lisa S Kearns; Linda Clarke; David A Mackey; Alex W Hewitt; Ian A Trounce; Alice Pébay

doi:10.18632/aging.101231

Mitochondrial replacement in an iPSC model of Leber's hereditary optic neuropathy

Aging (Albany NY). 2017 Apr;9(4):1341-1350. doi: 10.18632/aging.101231.

Authors

Raymond C B Wong^{1

2}, Shiang Y Lim³, Sandy S C Hung^{1

2}, Stacey Jackson^{1

2}, Shahnaz Khan^{1

2}, Nicole J Van Bergen^{1

2}, Elisabeth De Smit^{1

2}, Helena H Liang^{1

2}, Lisa S Kearns^{1

2}, Linda Clarke^{1

2}, David A Mackey^{4

5}, Alex W Hewitt^{1

2

5}, Ian A Trounce^{1

2

6}, Alice Pébay^{1

2

6}

Affiliations

¹ Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia.
² Department of Surgery, Ophthalmology, the University of Melbourne, Melbourne, Australia.
³ O'Brien Institute Department, St Vincent's Institute of Medical Research, Victoria, Australia.
⁴ Centre for Ophthalmology and Vision Science, University of Western Australia, Lions Eye Institute, Nedlands, Australia.
⁵ School of Medicine, Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
⁶ Co-senior authors.

Abstract

Cybrid technology was used to replace Leber hereditary optic neuropathy (LHON) causing mitochondrial DNA (mtDNA) mutations from patient-specific fibroblasts with wildtype mtDNA, and mutation-free induced pluripotent stem cells (iPSCs) were generated subsequently. Retinal ganglion cell (RGC) differentiation demonstrates increased cell death in LHON-RGCs and can be rescued in cybrid corrected RGCs.

Keywords: Leber’s hereditary optic neuropathy; cybrid; disease model; induced pluripotent stem cells; retinal ganglion cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis
Cell Death
Cell Differentiation
DNA, Mitochondrial / genetics*
DNA, Mitochondrial / metabolism
DNA, Mitochondrial / therapeutic use
Genetic Therapy / methods*
Humans
Induced Pluripotent Stem Cells*
Microsatellite Repeats
Mitochondria / genetics*
Optic Atrophy, Hereditary, Leber / therapy*
Retinal Ganglion Cells / pathology
Stem Cell Transplantation / methods*
Superoxides / metabolism

Substances

DNA, Mitochondrial
Superoxides