Increased retinal mtDNA damage in the CFH variant associated with age-related macular degeneration

Deborah A. Ferrington, Rebecca J. Kapphahn, Michaela M. Leary, Shari R. Atilano, Marcia R. Terluk, Pabalu Karunadharma, George Kuei Jie Chen, Rinki Ratnapriya, Anand Swaroop, Sandra R. Montezuma, M. Cristina Kenney

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


Age-related macular degeneration (AMD) is a major cause of blindness among the elderly in the developed world. Genetic analysis of AMD has identified 34 high-risk loci associated with AMD. The genes at these high risk loci belong to diverse biological pathways, suggesting different mechanisms leading to AMD pathogenesis. Thus, therapies targeting a single pathway for all AMD patients will likely not be universally effective. Recent evidence suggests defects in mitochondria (mt) of the retinal pigment epithelium (RPE) may constitute a key pathogenic event in some AMD patients. The purpose of this study is to determine if individuals with a specific genetic background have a greater propensity for mtDNA damage. We used human eyebank tissues from 76 donors with AMD and 42 age-matched controls to determine the extent of mtDNA damage in the RPE that was harvested from the macula using a long extension polymerase chain reaction assay. Genotype analyses were performed for ten common AMD-associated nuclear risk alleles (ARMS2, TNFRSF10A, CFH, C2, C3, APOE, CETP, LIPC, VEGF and COL10A1) and mtDNA haplogroups. Sufficient samples were available for genotype association with mtDNA damage for TNFRSF10A, CFH, CETP, VEGFA, and COL10A1. Our results show that AMD donors carrying the high risk allele for CFH (C) had significantly more mtDNA damage compared with donors having the wild-type genetic profile. The data from an additional 39 donors (12 controls and 27 AMD) genotyped for CFH alleles further supported these findings. Taken together, these studies provide the rationale for a more personalized approach for treating AMD by uncovering a significant correlation between the CFH high risk allele and accelerated mtDNA damage. Patients harboring this genetic risk factor may benefit from therapies that stabilize and protect the mt in the RPE.

Original languageEnglish (US)
Pages (from-to)269-277
Number of pages9
JournalExperimental Eye Research
StatePublished - Apr 1 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Ltd.


  • Age-related macular degeneration
  • Complement factor H
  • Eyebank tissue
  • Haplogroups
  • Inflammation
  • Mitochondria
  • MtDNA


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