April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Characteristics of Mitochondrial DNA Variants in Age-Related Macular Degeneration Retinas
Author Affiliations & Notes
  • M. C. Kenney
    Ophthalmology, Univ of California-Irvine, Orange, California
  • S. R. Atilano
    Ophthalmology, Univ of California-Irvine, Orange, California
  • M. Chwa
    Ophthalmology, Univ of California-Irvine, Orange, California
  • D. S. Boyer
    Retina-Vitreous Associates Medical Group, Beverly Hills, California
  • G. Chak
    University of Rochester, Rochester, New York
  • E. Yang
    Northwestern University, Chicago, Illinois
  • S. Chinichian
    Ophthalmology, Univ of California-Irvine, Orange, California
  • P. Coskun
    Center for Molecular and Mitochondrial Medicine and Genetics, Department of Biological Chemistry, Univ of California-Irvine, Irvine, California
  • D. C. Wallace
    Center for Molecular and Mitochondrial Medicine and Genetics, Department of Biological Chemistry, Univ of California-Irvine, Irvine, California
  • N. Udar
    Ophthalmology, Univ of California-Irvine, Orange, California
  • Footnotes
    Commercial Relationships  M.C. Kenney, None; S.R. Atilano, None; M. Chwa, None; D.S. Boyer, None; G. Chak, None; E. Yang, None; S. Chinichian, None; P. Coskun, None; D.C. Wallace, None; N. Udar, None.
  • Footnotes
    Support  Discovery Eye Foundation, Guenther Foundation, Lincy Foundation, Iris and B. Gerald Cantor Foundation, Ko Family Foundation, Gilbert Foundation, Research to Prevent Blindness.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 3446. doi:
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      M. C. Kenney, S. R. Atilano, M. Chwa, D. S. Boyer, G. Chak, E. Yang, S. Chinichian, P. Coskun, D. C. Wallace, N. Udar; Characteristics of Mitochondrial DNA Variants in Age-Related Macular Degeneration Retinas. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3446.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To determine the mitochondrial DNA (mtDNA) variants in retinas, choroids and/or blood of patients with AMD. To identify the levels of mtDNA heteroplasmy present in retinal mtDNA.

Methods: : Total DNA was extracted from retinas, choroids and/or blood from 13 normal (mean age 79.8, range 56 to 97) and 9 AMD subjects (mean age 81.5, range 69-93). Blood samples were collected from 141 AMD (average age 79, range 59-95) and 144 age-matched control subjects (average age 74, range 54-93) and total DNA was isolated. Samples were analyzed by Long extension-PCR (LX-PCR) amplification, restriction fragment length polymorphism (RFLP) and/or sequencing at the UCLA Sequencing and Genotype Core. Analyses were performed using the Mutation Surveyor program and GraphPad Prism software.

Results: : LX-PCR of the blood samples showed a prominent band of intact mtDNA (~16.2kb) while the retinal samples had increased signs of rearrangements/mutation represented by smaller sized-bands. Sequencing showed SNP heteroplasmy and length heteroplasmy in the retinal mtDNA. Other SNP variations were found in the AMD retinas. The common Leber’s Hereditary Optic Neuropathy single nucleotide polymorphisms G11778A, T14484C and G3460A were not found in any of the AMD samples studied.

Conclusions: : The retina has continuous high oxygen consumption rates to provide mitochondrial ATP for visual function. In addition, the retina is exposed continually to light causing further photo-oxidative damage to the cells. Our results support the hypothesis that AMD may be associated with alterations in mitochondrial energy metabolism including mtDNA base substitutions, heteroplasmy and total mtDNA rearrangements/mutations.

Keywords: age-related macular degeneration • mitochondria • genetics 
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