Age-dependent increase in miRNA-34a expression in the posterior pole of the mouse eye

Zeljka McBride, Krisztina I. Forward, Anthony T. Nguyen, Matthew H. Bordbari, Sharon L. Oltjen, Leonard M Hjelmeland

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Purpose: 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 down-regulation. 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.

Original languageEnglish (US)
Pages (from-to)1569-1578
Number of pages10
JournalMolecular Vision
Volume20
StatePublished - Nov 5 2014

ASJC Scopus subject areas

  • Ophthalmology

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    McBride, Z., Forward, K. I., Nguyen, A. T., Bordbari, M. H., Oltjen, S. L., & Hjelmeland, L. M. (2014). Age-dependent increase in miRNA-34a expression in the posterior pole of the mouse eye. Molecular Vision, 20, 1569-1578.