The Distribution of Mitochondrial Activity in Relation to Optic Nerve Structure

<h3>Background</h3> The observation of a buildup of mitochondria at the level of the lamina cribrosa in the optic nerve head has traditionally been attributed to axoplasmic stasis. However, this region is also the transition zone for myelination, resulting in differing energy requirements. <h3>Objective</h3> To investigate the relationship between myelination and mitochondrial activity in optic nerve tissue. <h3>Methods</h3> Histological, histochemical, and immunocytochemical techniques were used to demonstrate the distribution of myelin, cytochrome-<i>c</i>oxidase activity, and laminar structure in human optic nerve tissue. A study of rabbit optic nerve and retina and unmyelinated human pituitary stalk was also performed. Cytochrome-<i>c</i>oxidase activity in the human optic nerve tissue was measured using microphotometry. <h3>Results</h3> There was a striking inverse relationship between myelination and mitochondrial distribution in all tissue studied. Statistical analysis of microphotometric data showed this distribution to be highly significant. <h3>Conclusion</h3> We caution against the previous inference of a process of axoplasmic stasis and suggest that, instead, the distribution of mitochondria reflects the functional requirement of different regions of the ganglion cell axon. <h3>Clinical Relevance</h3> Optic neuropathy is associated with several inherited disorders of mitochondria. We suggest that a fine balance exists between energy demand and tissue function in the optic nerve, which may explain why optic nerve pathological features are seen in those with mitochondrial disease.