The retina is an exquisite target for defects of oxidative phosphorylation (OXPHOS) associated with mitochondrial impairment.
Retinal involvement occurs in two ways,
retinal dystrophy (
retinitis pigmentosa) and subacute or chronic
optic atrophy, which are the most common clinical entities. Both can present as isolated or virtually exclusive conditions, or as part of more complex, frequently multisystem syndromes. In most cases, mutations of
mtDNA have been found in association with mitochondrial retinopathy. The main genetic abnormalities of
mtDNA include mutations associated with
neurogenic muscle weakness, ataxia and retinitis pigmentosa (NARP) sometimes with earlier onset and increased severity (
maternally inherited Leigh syndrome, MILS), single large-scale deletions determining
Kearns-Sayre syndrome (KSS, of which
retinal dystrophy is a cardinal symptom), and mutations, particularly in
mtDNA-encoded ND genes, associated with
Leber hereditary optic neuropathy (LHON). However, mutations in nuclear genes can also cause mitochondrial retinopathy, including autosomal recessive phenocopies of LHON, and slowly progressive
optic atrophy caused by dominant or, more rarely, recessive, mutations in the fusion/mitochondrial shaping
protein OPA1, encoded by a nuclear gene on chromosome 3q29.