title: Dominant optic atrophy: updates on the pathophysiology and clinical manifestations of the optic atrophy 1 mutation.
abstract: OBJECTIVE
  Review recent advances in clinical and experimental studies of dominant optic atrophy (DOA) to better understand the complexities of pathophysiology caused by the optic atrophy 1 (OPA1) mutation.
  
  
  RESULTS
  DOA is the most commonly diagnosed inherited optic atrophy, causing progressive bilateral visual loss that begins early in life. During the past 25 years, there has been substantial progress in the understanding of the clinical, genetic, and pathophysiological basis of this disease. The histopathological hallmark of DOA is the primary degeneration of retinal ganglion cells, preferentially in the papillomacular bundle, which results temporal optic disc pallor and cecocentral scotomata in patients with DOA. Loss of OPA1 protein function by OPA1 gene mutations causes mitochondrial dysfunction because of the loss of mitochondrial fusion, impaired mitochondrial oxidative phosphorylation, increases in reactive oxygen species, and altered calcium homeostasis. These factors lead to apoptosis of retinal ganglion cells by a haploinsufficiency mechanism.
  
  
  CONCLUSIONS
  Improved understanding of the pathophysiology of DOA provides insights that can be used to develop therapeutic approaches to the DOA.
authors: aNeuro-Ophthalmology Service, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA bDepartment of Ophthalmology, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors: Bo Y
authors: BY
authors: Chun
authors: Joseph F
authors: JF
authors: Rizzo
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006706:Homeostasis; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D009154:Mutation; D029241:Optic Atrophy, Autosomal Dominant / Q000235:genetics* / Q000473:pathology*; D010085:Oxidative Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000473:pathology*
chemical_list: D017382:Reactive Oxygen Species; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human; D002118:Calcium