Mitochondrial optic neuropathies

• LHON
• mitochondria
• Leber's hereditary optic neuropathy

• LHON, Leber's hereditary optic neuropathy
• ROS, reactive oxygen species
• CEON, Cuban epidemic of optic neuropathy
• TAA, tobacco alcohol amblyopia
• mtPTP, mitochondrial permeability transition pore

Many optic neuropathies produce a similar clinical presentation. Investigations show that these optic neuropathies involve inherited or acquired impairments of mitochondrial function. Further reflection on these diseases and the selected sites of injury may provide a useful model of the pathophysiological mechanisms involved.

Recent studies have made clear the molecular basis of an intriguing optic neuropathy: Leber's hereditary optic neuropathy (LHON). This well characterised sub-acute affectation of the optic nerves, typically inherited through the maternal line, is due to mitochondrial dysfunction, usually demonstrated to be a consequence of one of three pathogenic point mutations in the mitochondrial DNA (mtDNA).1,2,3 All three of these pathogenic mutations affect complex I in the respiratory chain and the biochemical defect they induce is still under investigation. Both an impairment of energy production and/or a chronic increase of reactive oxygen species (ROS) are the potential consequences of the underlying LHON pathogenic mutations leading to optic nerve degeneration.4,5

The disease has many oddities. These include the disproportionate number of men who are affected and the amazing fact that a person will see well for two decades and then suddenly go blind, at about the same time, in both eyes.6

The LHON clinical presentation is stereotypic. A previously unaffected person, often a man in his 20s, will present with an acute onset of visual loss in one eye. Within a few days the patient notes a loss of colour vision, a significant loss of visual acuity, and a central visual field defect. Within weeks, the second eye almost always becomes involved in a remarkably similar way.6,7

With this clinical picture in mind, it was quite surprising when we saw tens of thousands of patients with bilateral symmetric visual loss and a similar presentation …