Na+ Channels Co-Localise With Mitochondrial Enzyme Activity in the Unmyelinated Part of the Human Optic Nerve Head

Abstract

Abstract: : Purpose:To study the distribution of Na+ channels and Na+/K+ATPase in the optic nerve head with relation to the distribution of mitochondrial enzyme activity, myelin and the position of the lamina cribrosa. Methods:We studied human optic nerves removed at corneal transplant retrieval. Optic nerve heads were sectioned longitudinally and Na+ channels, Na+/K+ATPase, cytochrome c oxidase and myelin were demonstrated by histochemical and immunohistochemical methods. Results:We found a high density of Na+ channel and Na+/K+ATPase immunolabelling in the unmyelinated prelaminar and laminar optic nerve. This distribution co-localised with the distribution of cytochrome c oxidase reflecting mitochondrial activity 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. Our results suggest that the increased mitochondrial density serves the increased energy requirements for electrical conduction in unmyelinated axons in the prelaminar and laminar optic nerve. Therefore, we suggest that the distribution of mitochondria in the optic nerve head reflects functional energy requirements rather than any mechanical restriction at the lamina cribrosa. This may explain why optic neuropathies occur in mitochondrial inherited diseases. Leber’s hereditary optic neuropathy specifically targets the optic nerve but other mitochondrial cytopathies including MERRF, MELAS, CPEO and Leighs syndrome are also associated with optic neuropathy. These diseases are rare but our findings also challenge the traditional hypotheses of optic nerve structure and function and may suggest an alternative approach to the study of commoner optic neuropathies such as glaucoma.

Keywords: anatomy • ion channels • mitochondria