Browse by author
Lookup NU author(s): Dr Patrick Yu Wai Man, Professor Patrick Chinnery
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
The ubiquitously expressed gene OPA1 is the main disease causing gene for autosomal dominant optic atrophy (ADOA). These patients present with bilateral reduction in visual acuity, central visual field defects and impaired color vision, secondary to the progressive loss of retinal ganglion cells (RGCs) and subsequent degeneration of the optic nerve. Up to now, it is not clear why a mutation in a ubiquitously expressed gene affects only RGCs and the optic nerve. Twenty-two-month-old Opa1 animals underwent a full examination following the Shirpa protocol. Weight, food intake and life span were monitored. Rotarod treadmill experiments were performed to assess neuromuscular function. Limb skeletal muscle was evaluated morphologically, mitochondrial cytochrome c oxidase (COX) activity was studied histochemically and mtDNA integrity was determined by long-range PCR. The Shirpa test showed that 33% of the Opa1 mice suffered from tremor and 52% of the Opa1 animals showed an abnormal clutching reflex. Control animals performed well in the accelerating Rotarod treadmill experiment whereas the Opa1 mice performed significantly worse. Skeletal muscle fibers were morphologically normal, had normal COX activity and showed no evidence of secondary mtDNA damage in contrast to patients with syndromic ADOA. We also found a highly significant difference in body weight. Our results demonstrate that OPA1 mutations affect not only RGCs but also other tissues and cell types, though to a lesser extent. In particular we found deficits in both neuromuscular and metabolic function. We therefore want to encourage clinicians to be vigilant about to extra-ocular manifestations in ADOA patients. (C) 2009 Elsevier Inc. All rights reserved.
Author(s): Alavi MV, Fuhrmann N, Nguyen HP, Yu-Wai-Man P, Heiduschka P, Chinnery PF, Wissinger B
Publication type: Article
Publication status: Published
Journal: Experimental Neurology
Year: 2009
Volume: 220
Issue: 2
Pages: 404-409
ISSN (print): 0014-4886
ISSN (electronic): 1090-2430
Publisher: Academic Press
URL: http://dx.doi.org/10.1016/j.expneurol.2009.09.026
DOI: 10.1016/j.expneurol.2009.09.026
Altmetrics provided by Altmetric
