June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
SIRT1 Regulates Cell Survival, Collagen VI Expression of Human TM Cells and Permeability Of Endothelial Cells of Schlemm’s Canal
Author Affiliations & Notes
  • yan Dai
    Medicine, Boston University School of Medicine, Boston, MA
  • Audrey Hagiwara
    Medicine, Boston University School of Medicine, Boston, MA
  • Heba Ijaz
    Medicine, Boston University School of Medicine, Boston, MA
  • Christopher Uherek
    Ophthalmology, Boston University School of Medicine, Boston, MA
  • Paloma Borrajo Liton
    Department of Ophthalmology, Duke University, Durham,, NC
  • Elizabeth Cho
    Medicine, Boston University School of Medicine, Boston, MA
  • Haiyan Gong
    Ophthalmology, Boston University School of Medicine, Boston, MA
  • Footnotes
    Commercial Relationships yan Dai, None; Audrey Hagiwara, None; Heba Ijaz, None; Christopher Uherek, None; Paloma Liton, None; Elizabeth Cho, None; Haiyan Gong, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 3304. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      yan Dai, Audrey Hagiwara, Heba Ijaz, Christopher Uherek, Paloma Borrajo Liton, Elizabeth Cho, Haiyan Gong; SIRT1 Regulates Cell Survival, Collagen VI Expression of Human TM Cells and Permeability Of Endothelial Cells of Schlemm’s Canal. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3304.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: SIRT1 (silence information regulator 1) is a histone deacetylase, which has been shown to play an important role in the regulation of metabolism, cell survival and organismal lifespan. Age-related loss of SIRT1 has been implicated in a number of several age-related diseases. Primary open angle glaucoma (POAG) is an age-related disease; cell death, matrix accumulation in the trabecular meshwork (TM) cell and decreased permeability of Schlemm’s canal (SC) endothelium were reported in POAG eyes. The goal of this study is to determine the role of SIRT1 in regulation of TM cell survival, matrix expression, and permeability of SC endothelial cells.

Methods: SIRT1 protein level in TM cells from human eyes (HTM) was analyzed by western blot analysis with anti-SIRT1 antibody. Cell viability by SIRT1 inhibitor Sirtinol or activator SRT1720 was monitored using the MTS assay. The effect of collagen VI expression by Sirtinol in HTM cells was determined by qRT-PCR, the permeability of SC cell by Sirtinol was determined by monitoring TEERs in a transwell SC cell culture.

Results: <br /> Our data shows that SIRT1 is expressed in primary HTM cells. Treatment of HTM cells with Sirtinol, a SIRT1 inhibitor at 50uM and 100uM, significantly reduces HTM cells survival up to 3 fold compared to vehicle control, while treatment with a SIRT1 activator, SRT1720 at 50nM increases cell survival. Moreover, SIRT1 inhibition up-regulates matrix collagen VI mRNA level up to 2.5 fold which has been shown significantly increased in the TM of POAG eyes. In addition, we demonstrated that SIRT1 inhibition with Sirtinol decreases 2-fold permeability of SC cell compared to control, which is an important contribution factor to increased outflow resistance in POAG. Thus, we demonstrate for the first time that SIRT1 regulates cell survival and matrix collagen VI expression of HTM cells and permeability of SC cells.

Conclusions: Our data suggests that SIRT1 may play an important role in the pathogenesis of glaucoma by its ability to regulate HTM cell survival and matrix collagen VI expression, as well as permeability of SC cells. Modulation of SIRT1 activity might constitute a novel approach for the treatment of ocular hypertension and glaucoma.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×