Sirtuin 1 participates in the process of age-related retinal degeneration

Biochem Biophys Res Commun. 2015 Dec 4-11;468(1-2):167-72. doi: 10.1016/j.bbrc.2015.10.139. Epub 2015 Oct 30.

Abstract

Background: The process of aging involves retinal cell damage that leads to visual dysfunction. Sirtuin (Sirt) 1 can prevent oxidative stress, DNA damage, and apoptosis. In the present study, we measured the expression of Sirt1 as a functional regulator in the retina during the aging process.

Methods: The visual function and Sirt1 expression in young (1 month) and old (19 months) Sprague-Dawley (SD) rats. Electroretinogram (ERG) and real-time polymerase chain reaction (PCR) or Western blotting were performed. Resveratrol, an activator of Sirt1, was orally administered to SD rats at a dose of 5 mg/kg/day for 19 months. The expression of Sirt1, brain-derived neurotrophic factor (BDNF), and tropomyosin receptor kinase B (TrkB) was evaluated in the retinas of mice that did and did not receive resveratrol treatment. Apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay.

Results: With decreasing b-wave amplitude, the expression level of Sirt1 was significantly reduced in aged retinas compared to that in young retinas. After 19 months of treatment with resveratrol, the Sirt1 expression level and b-wave amplitude increased. In old rats treated with resveratrol, the expression levels of BDNF and TrkB were up-regulated. Compared to young retinas, the aged retinas exhibited higher apoptosis, but resveratrol delayed this process.

Conclusions: Our data demonstrated a reduction of Sirt1 expression during the aging process of the retina, but enhancing Sirt1 expression reversed the degeneration of the retina. These results suggested that increasing Sirt1 expression may protect retinal neurons and visual function via regulating neurotrophin and its receptor.

Keywords: Apoptosis; BDNF; Retina; Sirtuin; Visual function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Aging / pathology*
  • Animals
  • Apoptosis
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Electroretinography
  • Gene Expression Regulation
  • Male
  • Mice
  • Rats, Sprague-Dawley
  • Receptor, trkB / genetics
  • Receptor, trkB / metabolism
  • Retina / metabolism
  • Retina / pathology*
  • Retinal Degeneration / genetics*
  • Retinal Degeneration / metabolism
  • Retinal Degeneration / pathology*
  • Sirtuin 1 / genetics*
  • Sirtuin 1 / metabolism
  • Up-Regulation*

Substances

  • Brain-Derived Neurotrophic Factor
  • Receptor, trkB
  • Sirtuin 1