title: Age-dependent increase in miRNA-34a expression in the posterior pole of the mouse eye.
abstract: OBJECTIVE
  MicroRNA-34a (miR-34a) has been implicated in neurodegeneration. MiR-34a belongs to a signaling network involving p53 and Sirt-1. This network responds to DNA damage with further downstream signals that induce senescence or apoptosis. Our goal was to measure the expression level of miR-34a in the mouse retina and RPE as a function of age.
  
  
  METHODS
  The age-dependent change in miR-34a expression was quantified using a real-time PCR (RT-PCR) assay on microRNA isolates from eye tissue: the retina and RPE/choroid (4, 18, 24, and 32 months of age). Tissue localization of miR-34a was determined by in situ hybridization (ISH) for a series of time points. Expression of the miR-34a target gene Sirt1 was analyzed using RT-PCR and immunohistochemistry.
  
  
  RESULTS
  MiR-34a examined with real-time PCR showed a linear increase in expression with age when compared to that of 4-month-old mice. However, the level of expression between the 24 and 32-month-old animals showed mild downregulation. An age-related increase in miR-34a expression was confirmed in the mouse eye using in situ hybridization. An inverse relationship between the levels of expression of miR-34a and its target Sirt1 mRNA was found at 18 and 24 months of age.
  
  
  CONCLUSIONS
  Our data showed that miR-34a expression increased in the retina and RPE with age. The level of DNA damage in mitochondria in the retina and RPE followed a similar time course. This suggests that miR-34a may play a role in the senescence and apoptosis of the retina and RPE cells in the aging eye.
authors.affiliation: UC Davis School of Medicine, Department of Ophthalmology, Vitreoretinal Research Lab, Davis, CA.
authors.forename: Zeljka
authors.initials: Z
authors.lastname: Smit-McBride
authors.affiliation: UC Davis School of Medicine, Department of Ophthalmology, Vitreoretinal Research Lab, Davis, CA.
authors.forename: Krisztina I
authors.initials: KI
authors.lastname: Forward
authors.affiliation: UC Davis School of Medicine, Department of Ophthalmology, Vitreoretinal Research Lab, Davis, CA.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Nguyen
authors.affiliation: UC Davis School of Medicine, Department of Ophthalmology, Vitreoretinal Research Lab, Davis, CA.
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Bordbari
authors.affiliation: UC Davis School of Medicine, Department of Ophthalmology, Vitreoretinal Research Lab, Davis, CA.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Oltjen
authors.affiliation: UC Davis School of Medicine, Department of Ophthalmology, Vitreoretinal Research Lab, Davis, CA.
authors.forename: Leonard M
authors.initials: LM
authors.lastname: Hjelmeland
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D002829:Choroid / Q000254:growth & development / Q000378:metabolism*; D004249:DNA Damage; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000254:growth & development / Q000378:metabolism*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism
chemical_list: C551848:MIRN34a microRNA, mouse; D035683:MicroRNAs; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1