Human iPSC disease modelling reveals functional and structural defects in retinal pigment epithelial cells harbouring the m.3243A > G mitochondrial DNA mutation.

ABSTRACT: The m.3243A > G mitochondrial DNA mutation was originally described in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. The phenotypic spectrum of the m.3243A > G mutation has since expanded to include a spectrum of neuromuscular and ocular manifestations, including reduced vision with retinal degeneration, the underlying mechanism of which remains unclear. We used dermal fibroblasts, from patients with retinal pathology secondary to the m.3243A > G mutation to generate heteroplasmic induced pluripotent stem cell (hiPSC) clones. RPE cells differentiated from these hiPSCs contained morphologically abnormal mitochondria and melanosomes, and exhibited marked functional defects in phagocytosis of photoreceptor outer segments. These findings have strikin

SUBMITTER: Chichagova V 

PROVIDER: S-EPMC5615077 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature