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Mitochondria in Retinal Neurodegeneration and Stem Cell Models

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Regenerative Biology of the Eye

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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Abstract

Defects in mitochondrial energetics result in several retinal diseases, providing unresolved clues to why some retinal neurons are specifically affected by mitochondrial dysfunction. The central mitochondrial pathway of energy generation—oxidative phosphorylation—presents unique challenges for unravelling the genetic and molecular mechanisms of neuronal susceptibility to energetic failure. This is due to the chimeric assembly of the constituent enzyme complexes from subunits encoded by both the mitochondrial (mt) DNA and nuclear genome. Stem cell modelling of mtDNA and nuclear gene-linked retinal disease hold great promise to advance this understanding, while at the same time providing new therapeutic insights. This unique genetics also has profound implications for stem cell biology. Recent discoveries place regulation of oxidative phosphorylation at the centre of cellular differentiation signalling. These evolving concepts are reviewed here, from oxidative phosphorylation and retinal disease consequences of energetic failure; to mitochondria in stem cells, differentiation, and epigenetic modulation of nuclear gene expression.

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Abbreviations

ADOA:

Autosomal dominant optic atrophy

AMD:

Age-related macular degeneration

ATP:

Adenosine triphosphate

CMT:

Charcot–Marie–Tooth

CPEO:

Chronic progressive external ophthalmoplegia

ESCs:

Embryonic stem cells

GWAS:

Genome wide association studies

iPSCs:

Induced pluripotent stem cells

KSS:

Kearns–Sayre syndrome

LHON:

Leber hereditary optic neuropathy

MELAS:

Mitochondrial encephalopathy lactic acidosis and stroke-like episodes

mtDNA:

Mitochondrial DNA

NAD:

Nicotinamide adenine dinucleotide (oxidised)

NADH:

Nicotinamide adenine dinucleotide (reduced)

NARP:

Neurogenic atrophy and retinitis pigmentosa syndrome

OXPHOS:

Oxidative phosphorylation

POAG:

Primary open angle glaucoma

RGCs:

Retinal ganglion cells

RPE:

Retinal pigment epithelium

TIM:

Translocase of the inner membrane

TOM:

Translocase of the outer membrane

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Authors and Affiliations

  1. Centre for Eye Research Australia and the Department of Ophthalmology, Royal Victorian Eye and Ear Hospital, University of Melbourne, 32 Gisborne Street, East Melbourne, VIC, 3002, Australia

    Ian A. Trounce

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  1. Ian A. Trounce
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Correspondence to Ian A. Trounce .

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  1. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Department of Ophthalmology, The University of Melbourne, East Melbourne, Victoria, Australia

    Alice PĂ©bay

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Trounce, I.A. (2014). Mitochondria in Retinal Neurodegeneration and Stem Cell Models. In: PĂ©bay, A. (eds) Regenerative Biology of the Eye. Stem Cell Biology and Regenerative Medicine. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0787-8_2

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