June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Age-Dependent Ocular Changes in Sirt6 Knockout Mice
Author Affiliations & Notes
  • Alexey Obolensky
    Center for Retinal and Macular Degenerations, Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
  • Victoria Peshti
    The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel
  • Yariv Kanfi
    The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel
  • Haim Cohen
    The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel
  • Eyal Banin
    Center for Retinal and Macular Degenerations, Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
  • Footnotes
    Commercial Relationships Alexey Obolensky, None; Victoria Peshti, None; Yariv Kanfi, None; Haim Cohen, None; Eyal Banin, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 6078. doi:
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    • Get Citation

      Alexey Obolensky, Victoria Peshti, Yariv Kanfi, Haim Cohen, Eyal Banin; Age-Dependent Ocular Changes in Sirt6 Knockout Mice. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6078.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Sirtuins (Silent Information Regulator Two, Sirt)) are a family of proteins with histone deacetylase and/or mono-ribosyltransferase activity. Overexpression of sirtuins in many organisms promotes longevity, while their absence may cause early senescence. The purpose of the present study was to assess the role of Sirt6 in retinal aging.

Methods: Retinal function and structure were compared over the span of 10 months between three groups of mice: homozygous Sirt6-/- knockouts, heterozygous Sirt6+/- (hz), and normal wild type (wt) mice. At 1, 6 and 10 months of age, retinal function was evaluated by electroretinography (ERG) and quantitative histologic techniques were used to assess retinal structure.

Results: Sirt6-/- mice demonstrated a high rate of early postnatal lethality and were characterized by developmental retardation, low body weight and a short lifespan. By 5-6 months of age, severe corneal injury was often observed in Sirt6-/- mice including corneal scarring, vascularization, signs of stromal edema and inflammation. At 1 month of age Sirt6-/- mice demonstrated a trend toward lower dark-adapted b-wave amplitudes as compared with wt animals. At this time, no changes in outer nuclear layer (ONL) thickness were found between wt and Sirt6-/- mice. However, at 6 months, dark adapted ERG responses were significantly (by 45% at highest stimulus intensity) reduced in Sirt6-/- animals compared with wt control. Cone function was also markedly affected, being 2.5-3-fold lower in Sirt6-/- mice. ONL thickness was significantly reduced in the central retina of Sirt6-/- mice (p<0.02) at this time point. At 10 months of age severe impairment of retinal function was observed in Sirt6-/- mice, with dark-adapted b-wave amplitudes reduced by 39% and cone-flicker ERG amplitudes reduced by 75% as compared with wt. Further thinning of the ONL not only in the central but also in the mid-peripheral and peripheral retina was evident, accompanied by thinning of other retinal layers. No significant differences were found in ERG amplitudes between wt and hz mice up to the age of 10 months.

Conclusions: Sirt6-/- mice demonstrate age-dependent corneal injury and impairment of retinal function accompanied by thinning of the ONL. The results may suggest a role for Sirt6 in maintaining survival and function of retinal cells over time.

Keywords: 688 retina • 413 aging • 510 electroretinography: non-clinical  
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