Assessing mitochondrial DNA nucleotide changes in spontaneous optic neuropathies

Purpose: The high mutation rate in the mitochondrial genome makes it difficult to be certain about mtDNA pathology, and yet we now recognize several primary and provisional Leber hereditary optic neuropathy (LHON) mutations (which are commonly pathologic) and a larger number of secondary LHON mutations (which are often associated with certain primary LHON mutations and may contribute to pathogenicity), haplogroup-specific mitochondrial DNA (mtDNA) sequence variants, and simple polymorphisms (which are not commonly pathologic). Conclusions: An enormous amount of information is now known about mitochondria, the apparent dependence of the optic nerve on mitochondria, various metabolic effects of primary LHON mutations, and certain ways in which these nucleotide changes might harm the optic nerve are discussed.