Mouse models of dominant optic atrophy: What do they tell us about the pathophysiology of visual loss?

Dominant optic atrophy (DOA) is the most common inherited optic neuropathy affecting one in every 12,000 people. It presents with bilateral visual loss, central visual fields defects, colour vision disturbance and optic disc pallor. OPA1 has been identified as the responsible gene and its locus mapped to chromosome 3q28-q29. Mutations in this gene are responsible for the clinical phenotype in over 70% of patients with DOA. Histopathological studies in tissues from patients reveal loss of retinal ganglion cells but the paucity of viable human tissue has raised the importance of an animal model to study the pathophysiology of the disease. In the last decade considerable work has gone into the generation of animal, most notably mouse, models of Opal DOA. Two murine models of DOA have been published, designated B6;C3-Opa1(Q285STOP) and B6;C3-Opa1(329-355del) and they provide valuable insights with respect to neurological and visual phenotyping, mitochondrial dysfunction, optic nerve and axonal changes, retinal ganglion cell depletion and dendritic atrophy. Here we summarise the current state of knowledge of the mechanisms of disease based on data from these models of Opal DOA. (C) 2010 Elsevier Ltd. All rights reserved.