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Abstract #10253 Published in IGR 6-1
The distributions of mitochondria and sodium channels reflect the specific energy requirements and conduction properties of the human optic nerve head
Barron MJ; Griffiths P; Turnbull DM; Bates D; Nichols PBritish Journal of Ophthalmology 2004; 88: 286-290
AIM: To study the normal distributions of mitochondria and voltage gated Na+ channels in the human optic nerve head in order to gain insight into the potential mechanisms of optic nerve dysfunction seen in the inherited optic neuropathies. METHODS: Five fresh frozen human optic nerves were studied. Longitudinally orientated, serial cryosections of optic nerve head were cut for mitochondrial enzyme histochemistry and immunolabeling for cytochrome c oxidase (COX) subunits and voltage gated Na+ channel subtypes (Nav 1.1, 1.2, 1.3, and 1.6). RESULTS: A high density of voltage gated Na+ channels (subtypes Nav 1.1, 1.3, and 1.6) in the unmyelinated, prelaminar, and laminar optic nerve was found. This distribution co-localized both with areas of high COX activity and strong immunolabeling for COX subunits I and IV. CONCLUSIONS: Increased numbers of mitochondria in the prelaminar optic nerve have previously been interpreted as indicating a mechanical hold up of axoplasmic flow at the lamina cribrosa. These results suggest that this increased mitochondrial density serves the higher energy requirements for electrical conduction in unmyelinated axons in the prelaminar and laminar optic nerve and is not a reflection of any mechanical restriction. This could explain why optic neuropathies typically occur in primary inherited mitochondrial diseases such as Leber's hereditary optic neuropathy, myoclonic epilepsy with ragged red fibers (MERRF), and Leigh's syndrome. Secondary mitochondrial dysfunction has also been reported in dominant optic atrophy, Friedreich's ataxia, tobacco alcohol amblyopia, Cuban epidemic optic neuropathy, and chloramphenicol optic neuropathy. These diseases are rare but these findings challenge the traditional theories of optic nerve structure and function and may suggest an alternative approach to the study of commoner optic neuropathies such as glaucoma.
Dr. M. J. Barron, Department of Neurology, School of Neurology, Neurobiology and Psychiatry, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK. m.j.barron@ncl.ac.uk
Classification:
2.14 Optic disc (Part of: 2 Anatomical structures in glaucoma)
3.3 Immunohistochemistry (Part of: 3 Laboratory methods)
