The Neuro-Ophthalmology of Mitochondrial Disease

• Type of Material: Article
• Authors: J. Alexander Fraser, Emory University; Valerie Biousse, Emory University; Nancy J Newman, Emory University
• Language: English
• Date: 2010-07-08
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.survophthal.2009.10.002
• Title of Journal or Parent Work: Survey of Ophthalmology
• ISSN: 0039-6257
• Volume: 55
• Issue: 4
• Start Page: 299
• End Page: 334
• Grant/Funding Information: Dr. Nancy J. Newman is a recipient of a Research to Prevent Blindness Lew R. Wasserman Merit Award.; This study was supported in part by a departmental grant (Department of Ophthalmology) from Research to Prevent Blindness, Inc., New York, NY, and by core grants P30-EY06360 (Department of Ophthalmology) from the National Institutes of Health, Bethesda, MD.
• Keywords: MELAS; pigmentary retinopathy; Leber hereditary optic neuropathy; neuro-ophthalmology; chronic progressive external ophthalmoplegia; Mitochondria; dominant optic atrophy; NARP; Kearns-Sayre syndrome
• Research Categories: Biology, Neuroscience; Health Sciences, Opthamology

Abstract

Mitochondrial diseases frequently manifest neuro-ophthalmologic symptoms and signs. Because of the predilection of mitochondrial disorders to involve the optic nerves, extraocular muscles, retina, and even the retrochiasmal visual pathways, the ophthalmologist is often the first physician to be consulted. Disorders caused by mitochondrial dysfunction can result from abnormalities in either the mitochondrial DNA or in nuclear genes which encode mitochondrial proteins. Inheritance of these mutations will follow patterns specific to their somatic or mitochondrial genetics. Genotype-phenotype correlations are inconstant, and considerable overlap may occur among these syndromes. The diagnostic approach to the patient with suspected mitochondrial disease entails a detailed personal and family history, careful ophthalmic, neurologic, and systemic examination, directed investigations, and attention to potentially life-threatening sequelae. Although curative treatments for mitochondrial disorders are currently lacking, exciting research advances are being made, particularly in the area of gene therapy. Leber hereditary optic neuropathy, with its window of opportunity for timely intervention and its accessibility to directed therapy, offers a unique model to study future therapeutic interventions. Most patients and their relatives benefit from informed genetic counseling.