Research Paper Volume 9, Issue 4 pp 1341—1350

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

Raymond C.B. Wong 1, 2, , Shiang Y. Lim 3, , 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, ,

  • 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

received: March 25, 2017 ; accepted: April 23, 2017 ; published: April 29, 2017 ;

https://doi.org/10.18632/aging.101231
How to Cite

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.

Abbreviations

Cybrid: cyb; induced pluripotent stem cells: iPSCs; Leber hereditary optic neuropathy: LHON; Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke-like episodes: MELAS; mitochondrial: mt; retinal ganglion cells: RGCs.