title: Human retinal transmitochondrial cybrids with J or H mtDNA haplogroups respond differently to ultraviolet radiation: implications for retinal diseases.
abstract: BACKGROUND
  It has been recognized that cells do not respond equally to ultraviolet (UV) radiation but it is not clear whether this is due to genetic, biochemical or structural differences of the cells. We have a novel cybrid (cytoplasmic hybrids) model that allows us to analyze the contribution of mitochondrial DNA (mtDNA) to cellular response after exposure to sub-lethal dose of UV. mtDNA can be classified into haplogroups as defined by accumulations of specific single nucleotide polymorphisms (SNPs). Recent studies have shown that J haplogroup is high risk for age-related macular degeneration while the H haplogroup is protective. This study investigates gene expression responses in J cybrids versus H cybrids after exposure to sub-lethal doses of UV-radiation.
  
  
  RESULTS
  Cybrids were created by fusing platelets isolated from subjects with either H (n = 3) or J (n = 3) haplogroups with mitochondria-free (Rho0) ARPE-19 cells. The H and J cybrids were cultured for 24 hours, treated with 10 mJ of UV-radiation and cultured for an additional 120 hours. Untreated and treated cybrids were analyzed for growth rates and gene expression profiles. The UV-treated and untreated J cybrids had higher growth rates compared to H cybrids. Before treatment, J cybrids showed lower expression levels for CFH, CD55, IL-33, TGF-A, EFEMP-1, RARA, BCL2L13 and BBC3. At 120 hours after UV-treatment, the J cybrids had decreased CFH, RARA and BBC3 levels but increased CD55, IL-33 and EFEMP-1 compared to UV-treated H cybrids.
  
  
  CONCLUSIONS
  In cells with identical nuclei, the cellular response to sub-lethal UV-radiation is mediated in part by the mtDNA haplogroup. This supports the hypothesis that differences in growth rates and expression levels of complement, inflammation and apoptosis genes may result from population-specific, hereditary SNP variations in mtDNA. Therefore, when analyzing UV-induced damage in tissues, the mtDNA haplogroup background may be important to consider.
authors.affiliation: Gavin Herbert Eye Institute, University California Irvine, Irvine, California, United States of America.
authors.forename: Deepika
authors.initials: D
authors.lastname: Malik
authors.affiliation: Gavin Herbert Eye Institute, University California Irvine, Irvine, California, United States of America.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Hsu
authors.affiliation: Gavin Herbert Eye Institute, University California Irvine, Irvine, California, United States of America.
authors.forename: Payam
authors.initials: P
authors.lastname: Falatoonzadeh
authors.affiliation: Gavin Herbert Eye Institute, University California Irvine, Irvine, California, United States of America.
authors.forename: Javier
authors.initials: J
authors.lastname: Cáceres-del-Carpio
authors.affiliation: Gavin Herbert Eye Institute, University California Irvine, Irvine, California, United States of America; Department of Ophthalmology, El-Minya University, El-Minya, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Tarek
authors.affiliation: Gavin Herbert Eye Institute, University California Irvine, Irvine, California, United States of America.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Chwa
authors.affiliation: Gavin Herbert Eye Institute, University California Irvine, Irvine, California, United States of America.
authors.forename: Shari R
authors.initials: SR
authors.lastname: Atilano
authors.affiliation: Gavin Herbert Eye Institute, University California Irvine, Irvine, California, United States of America.
authors.forename: Claudio
authors.initials: C
authors.lastname: Ramirez
authors.affiliation: Gavin Herbert Eye Institute, University California Irvine, Irvine, California, United States of America; Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Nesburn
authors.affiliation: Retina-Vitreous Associates Medical Group; Beverly Hills, California, United States of America.
authors.forename: David S
authors.initials: DS
authors.lastname: Boyer
authors.affiliation: Gavin Herbert Eye Institute, University California Irvine, Irvine, California, United States of America.
authors.forename: Baruch D
authors.initials: BD
authors.lastname: Kuppermann
authors.affiliation: Tulane Center for Aging, Tulane University, New Orleans, Louisiana, United States of America.
authors.forename: S Michal
authors.initials: SM
authors.lastname: Jazwinski
authors.affiliation: Tulane Center for Aging, Tulane University, New Orleans, Louisiana, United States of America.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Miceli
authors.affiliation: Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia and Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Wallace
authors.affiliation: Gavin Herbert Eye Institute, University California Irvine, Irvine, California, United States of America.
authors.forename: Nitin
authors.initials: N
authors.lastname: Udar
authors.affiliation: Gavin Herbert Eye Institute, University California Irvine, Irvine, California, United States of America; Department of Pathology and Laboratory Medicine, University California Irvine, Irvine, California, United States of America.
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Kenney
mesh_terms: D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012160:Retina / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: D004272:DNA, Mitochondrial