June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Age-Associated Changes of mTOR Signaling in The Retinal Pigment Epithelium
Author Affiliations & Notes
  • Bo Yu
    Ophthalmology, The University of Texas Medical Branch at Galveston, Galveston, TX
  • Zhen-Yang Zhao
    Ophthalmology, The University of Texas Medical Branch at Galveston, Galveston, TX
  • Yiqin Zuo
    Ophthalmology, The University of Texas Medical Branch at Galveston, Galveston, TX
  • Pei Xu
    Ophthalmology, The University of Texas Medical Branch at Galveston, Galveston, TX
  • Paul Sternberg
    the Vanderbilt Eye Institute, Vanderbilt University, Nashville, TN
  • Yan Chen
    Ophthalmology, The University of Texas Medical Branch at Galveston, Galveston, TX
  • Footnotes
    Commercial Relationships Bo Yu, None; Zhen-Yang Zhao, None; Yiqin Zuo, None; Pei Xu, None; Paul Sternberg, None; Yan Chen, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 1381. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Bo Yu, Zhen-Yang Zhao, Yiqin Zuo, Pei Xu, Paul Sternberg, Yan Chen; Age-Associated Changes of mTOR Signaling in The Retinal Pigment Epithelium. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1381.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: The mammalian target of rapamycin (mTOR)-mediated signaling network is a central regulator of aging. Inhibiting mTOR is a promising strategy for treating various age-related diseases including macular degeneration (AMD). The goals of our current study are to investigate whether mTOR signaling has age- and/or pathology-associated changes in the retinal pigment epithelium (RPE) and to explore the functional roles of mTOR pathway in RPE aging and degeneration.

Methods: Post-mitotic aging of cultured human RPE cells was induced by altering the medium nutrient compositions. Basal and stimulated activities of mTOR were determined by measuring the phosphorylation status of downstream substrate proteins including S6K and S6. Subcellular localization of mTOR was evaluated using flat mounts of RPE/choroid tissue obtained from wild type and knockout mice deficient of nuclear factor erythroid 2-related factor 2 (Nrf2) at different ages. The in vivo activity of mTOR was further assessed by immunofluorescence staining of histology sections from young and aged animals.

Results: In the newly established in vitro aging model, post-mitotic RPE cells expressed typical markers of aging, such as senescence associated-beta-galactosidase and CDK inhibitor p16. Aged RPE cells showed increased sensitivity to amino acid-induced S6 phosphorylation and increased staining of lysosome marker proteins. Elevated mTOR activity was also detected in aged RPE in vivo. In addition, immunostaining of RPE flat mounts showed increased lysosome distribution of mTOR with aging.

Conclusions: mTOR-mediated signaling pathway displayed age-related changes in the RPE. The subcellular location of mTOR is related to its activity and can be influenced by lysosome function during the processes of RPE aging and degeneration. (Supported by NIH grants EY 019706, EY 021937 and Research to Prevent Blindness, Inc.)

Keywords: 412 age-related macular degeneration • 413 aging • 701 retinal pigment epithelium  
×
×

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.

×