Mitochondrial DNA damage and repair in rpe associated with aging and age-related macular degeneration

Haijiang Lin, Haifeng Xu, Fong Qi Liang, Hao Liang, Praveena Gupta, Anna N. Havey, Michael E. Boulton, Bernard F. Godley

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

PURPOSE. Mitochondrial DNA (mtDNA) damage may be associated with age-related diseases, such as age-related macular degeneration (AMD). The present study was designed to test whether the frequency of mtDNA damage, heteroplasmic mtDNA mutations, and repair capacity correlate with progression of AMD. METHODS. Macular and peripheral RPE cells were isolated and cultured from human donor eyes with and without AMD. The stages of AMD were graded according to the Minnesota Grading System. Confluent primary RPE cells were used to test the frequency of endogenous mtDNA damage by quantitative PCR. Mutation detection kits were used to detect heteroplasmic mtDNA mutation. To test the mtDNA repair capacity, cultured RPE cells were allowed to recover for 3 and 6 hours after exposure to H<inf>2</inf>O<inf>2</inf>, and repair was assessed by quantitative PCR. The levels of human OGG1 protein, which is associated with mtDNA repair, were analyzed by Western blot. RESULTS. This study showed that mtDNA damage increased with aging and that more lesions occurred in RPE cells from the macular region than the periphery. Furthermore, mtDNA repair capacity decreased with aging, with less mtDNA repair capacity in the macular region compared with the periphery in samples from aged subjects. Most interestingly, the mtDNA damage was positively correlated with the grading level of AMD, whereas repair capacity was negatively correlated. In addition, more mitochondrial heteroplasmic mutations were detected in eyes with AMD. CONCLUSIONS. These data show macula-specific increases in mtDNA damage, heteroplasmic mutations, and diminished repair that are associated with aging and AMD severity.

Original languageEnglish (US)
Pages (from-to)3521-3529
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number6
DOIs
StatePublished - May 2011

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Macular Degeneration
Mitochondrial DNA
DNA Repair
DNA Damage
Mutation
Polymerase Chain Reaction
Cultured Cells
Western Blotting

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

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Mitochondrial DNA damage and repair in rpe associated with aging and age-related macular degeneration. / Lin, Haijiang; Xu, Haifeng; Liang, Fong Qi; Liang, Hao; Gupta, Praveena; Havey, Anna N.; Boulton, Michael E.; Godley, Bernard F.

In: Investigative Ophthalmology and Visual Science, Vol. 52, No. 6, 05.2011, p. 3521-3529.

Research output: Contribution to journalArticle

Lin, Haijiang ; Xu, Haifeng ; Liang, Fong Qi ; Liang, Hao ; Gupta, Praveena ; Havey, Anna N. ; Boulton, Michael E. ; Godley, Bernard F. / Mitochondrial DNA damage and repair in rpe associated with aging and age-related macular degeneration. In: Investigative Ophthalmology and Visual Science. 2011 ; Vol. 52, No. 6. pp. 3521-3529.
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