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Invest Ophthalmol Vis Sci. 2009 Apr;50(4):1838-47. doi: 10.1167/iovs.08-2029. Epub 2008 Nov 7.

Adaptive optics scanning laser ophthalmoscopy images in a family with the mitochondrial DNA T8993C mutation.

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1
Department of Ophthalmology, University of California, San Francisco, California 94143-0730, USA.

Abstract

PURPOSE:

This study was designed to assess the effect of mitochondrial DNA (mtDNA) mutation T8993C on cone structure in a family expressing neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) syndrome.

METHODS:

Five family members were studied, using clinical examination, nerve conduction studies, perimetry, optical coherence tomography (OCT) measures of central retinal thickness, and electroretinography. High-resolution images of cone structure using adaptive optics scanning laser ophthalmoscopy (AOSLO) were obtained in four subjects with stable fixation. Cone spacing was compared to 18 age-similar normal subjects and converted to z-scores at each location where unambiguous cones were identified. Tissue levels of T8993C mutant heteroplasmy in blood and hair follicles were quantified using real-time allele-refractory mutations system (ARMS) quantitative polymerase chain reaction (qPCR).

RESULTS:

Subjects expressing the T8993C mutation showed varying levels of disease severity. The subject with the lowest mutant load (42%-54%) showed no neurologic or retinal abnormalities. The remaining four subjects with over 77% mutant load all expressed severe neurologic and/or retinal abnormalities. AOSLO images revealed three patterns of cone spacing: pattern 1, normal; pattern 2, increased cone spacing within a contiguous cone mosaic; and pattern 3, patchy cone loss with increased cone spacing. Visual function was most severely affected in pattern 3.

CONCLUSIONS:

High levels of T8993C mutant load were associated with severe neurologic or visual dysfunction, while lower levels caused no detectable abnormalities. Visual function was better in patients with a contiguous and regular cone mosaic. Patients expressing high levels of the mtDNA T8993C mutation show abnormal cone structure, suggesting normal mitochondrial DNA is necessary for normal waveguiding by cones.

PMID:
18997096
PMCID:
PMC4836613
DOI:
10.1167/iovs.08-2029
[Indexed for MEDLINE]
Free PMC Article
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