June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
CXCL13, an aging-related microglial-derived cytokine, promotes epithelial-mesenchymal transformation (EMT) in RPE cells
Author Affiliations & Notes
  • Wenxin Ma
    UNGIRD, National Eye Institute, Bethesda, Maryland, United States
  • Lian Zhao
    UNGIRD, National Eye Institute, Bethesda, Maryland, United States
  • Lijin Dong
    Genetic Engineering Facility, NEI, Bethesda, Maryland, United States
  • Maria M Campos
    Histopathology Core Facility, NEI, Bethesda, Maryland, United States
  • Robert N Fariss
    Biological Imaging Core, NEI, Bethesda, Maryland, United States
  • Wai T Wong
    UNGIRD, National Eye Institute, Bethesda, Maryland, United States
  • Footnotes
    Commercial Relationships   Wenxin Ma, None; Lian Zhao, None; Lijin Dong, None; Maria Campos, None; Robert Fariss, None; Wai Wong, None
  • Footnotes
    Support  NEI intramural research
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5375. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Wenxin Ma, Lian Zhao, Lijin Dong, Maria M Campos, Robert N Fariss, Wai T Wong; CXCL13, an aging-related microglial-derived cytokine, promotes epithelial-mesenchymal transformation (EMT) in RPE cells. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5375.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Age-related macular degeneration (AMD) has been associated with neuroinflammatory changes in the outer retina and as well as RPE disorganization that is evident as pigment clumping. Retinal microglia, the primary resident immune cell, demonstrate multiple aging changes, including changes in cytokine expression. In previous gene profiling experiments in retinal microglia, we had identified CXCL13 as a cytokine whose expression increased progressively with aging. As its cognate receptor, CXCR5, is expressed by RPE cells, we explored the ability of CXCL13 to drive interactions between microglia and RPE cells in ways potentially relevant to AMD pathogenesis.

Methods : RPE responses to recombinant CXCL13 stimulation were investigated using ARPE19 cells and mouse RPE-sclerochoroidal explants. A transgenic mouse model involving the use of a microglia-specific tamoxifen-inducible Cre recombinase (CX3CR1-CreER) was used to drive the overexpression of CXCL13 in microglia via a flox-STOP-flox-CXCL13 transgene. In vitro and in vivo responses were evaluated with rt-PCR, western blot and ELISA analyses, and immunohistochemistry.

Results : In vitro CXCL13 stimulation of RPE cells in (1) the ARPE19 cell-line and (2) in RPE-sclerochoroidal explants increased mRNA and protein expression of epithelial-to-mesenchymal transformation (EMT) gene markers (snail1, vimentin, fibronectin) and decreased RPE-expressed genes such as ZO1 and RPE65. In transgenic mice, tamoxifen-induction resulted in increased CXCL13 mRNA expression in retinal microglia and increased CXCL13 protein levels in the retina. Increased CXCL13 expression in vivo was correlated with RPE changes including structural disorganization, decreased RPE65 expression, and increased EMT marker (snail1, vimentin, fibronectin) expression.

Conclusions : Increased CXCL13-CXCR5 signaling from microglia to RPE cells was associated with in vitro and in vivo RPE changes and disorganization resembling features observed in AMD. CXCL13-CXCR5 signaling may be a potential mechanism connecting aging-related immune changes to retinal degeneration in AMD.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

×
×

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.

×