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Why is the optic nerve the canary in the coal mine of mitochondrial diseases?
Author(s) -
SADUN A
Publication year - 2013
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2013.3321.x
Subject(s) - optic nerve , axon , neuroscience , myelin , atrophy , optic neuropathy , retinal , retina , anatomy , pathology , medicine , biology , ophthalmology , central nervous system
Abstract Mitochondrial Optic Neuropathies (MON) present characteristic clinical and pathological features. Loss of visual acuity, dyschromatopsia and a central scotoma speak to involvement of the papillomacular bundle (PMB). Histopathology confirms this. These features are seen in hereditary diseases (Leber's Hereditary Optic Neuropathy—LHON and Dominant Optic Atrophy), Syndromes (such as MELAS, Wolfram's or FA), or toxic MONs. So why is the optic nerve involved so early and so often in mitochondrial disease? The brain weighs 2% of the body but consumes 20% of the body's oxygen. This expensive consumption of energy is largely due to the need for repolarization of the axon's membrane after each action potential. This is largely mitigated by myelin such that the sodium/potassium pumps only work at the Nodes of Ranvier. However, the retinal nerve fiber layer remains unmyelinated due to the need for inner retinal transparency. We present a mathematical model of these conditions that predicts the order of fiber loss in MON as a function of myelin and axon diameter. We demonstrate, with morphometry of postmortem samples of normal and LHON optic nerves, that this pattern is strictly observed.