April 2014
Volume 55, Issue 13
ARVO Annual Meeting Abstract  |   April 2014
The involvement of IL-17RC pathway in the inflammatory stimuli of the multipotent retinal stem cells
Author Affiliations & Notes
  • Shida Chen
    National eye institution, Bethesda, MD
    Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China
  • Defen Shen
    National eye institution, Bethesda, MD
  • Nicholas Popp
    National eye institution, Bethesda, MD
  • Jingsheng Tuo
    National eye institution, Bethesda, MD
  • Mones S Abu-Asab
    National eye institution, Bethesda, MD
  • Ting Xie
    Stowers Institute for Medical Research, Kansas City, MO
  • Chi-Chao Chan
    National eye institution, Bethesda, MD
  • Footnotes
    Commercial Relationships Shida Chen, None; Defen Shen, None; Nicholas Popp, None; Jingsheng Tuo, None; Mones Abu-Asab, None; Ting Xie, None; Chi-Chao Chan, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 3984. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Shida Chen, Defen Shen, Nicholas Popp, Jingsheng Tuo, Mones S Abu-Asab, Ting Xie, Chi-Chao Chan; The involvement of IL-17RC pathway in the inflammatory stimuli of the multipotent retinal stem cells. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3984.

      Download citation file:

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

  • Supplements

Purpose: Multipotent retinal stem cells (RSCs) from the adult mouse retina are capable of producing functional photoreceptor cells to replace degenerative and atrophic photoreceptor cells in animal models. Inflammasome activation has been implicated in the pathogenesis of age-related macular degeneration (AMD). The downstream effectors of inflammasome activation are maturation of IL-1β and IL-18, which can induce the expression of IL-17A in Th17 cells. IL-17A mediates signal transduction and pro-inflammatory activities through its receptor, IL-17RC, which may contribute to AMD pathogenesis. Additionally, IL-1β and IL-18 signals may lead to apoptosis. This study aimed to determine whether IL-1β and IL-18 could induce expression of IL-17A and IL-17RC and to characterize their effect on apoptosis in RSCs.

Methods: RSCs were cultured in culture medium for retinal stem cells supplemented with 5% Knockout Serum Replacement, EGF and FGF, and the cells doubled every 24 hours. The protein levels of IL-17RC, cleaved caspase-3, and cleaved-caspase-9 were detected by confocal immunofluorescent microscopy. Cells were treated with IL-1β (1ng/ml, 10ng/ml, and 100ng/ml) or IL-18 (1ng/ml, 10ng/ml, and 100ng/ml) for 24 hours. Expression of IL-6, IL-17A, and IL-17RC transcript was evaluated by quantitative RT-PCR.

Results: Naive RSCs expressed IL-17RC on the cell membrane and in the cytoplasm. Expression of IL-17RC mRNA increased by 2-fold when the cells were treated with the high dose of IL-1β (100ng/ml) but was enhanced in a dose-dependent manner when treated with IL-18. Treatment with IL-1β at 100ng/ml concentration induced a 3-fold increase in IL-6 mRNA expression. IL-18 treatment led to increased expression of IL-6 in a dose-dependent manner. IL-17A was not induced by either IL-1β or IL-18 treatment. IL-1β (100ng/ml) or IL-18 (10ng/ml) treatment induced expression of cleaved caspase-3 and cleaved-caspase-9 in the RSCs.

Conclusions: RSCs express IL-17 receptor, which is upregulated by IL-1β and IL-18. Neither IL-1β nor IL-18 treatment led to measurable IL-17A expression in this cell line. However, both IL-1β and IL-18, which are activated by inflammasome, can have pro-apoptotic effects on RSCs and may induce other pro-inflammatory cytokine produced by these cells.

Keywords: 648 photoreceptors • 557 inflammation • 426 apoptosis/cell death  

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.