June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Reactive microglia and the formation of Müller glia-derived retinal progenitors
Author Affiliations & Notes
  • Chris Zelinka
    Neuroscience, Ohio State University, Columbus, OH
  • Melissa Scott
    Neuroscience, Ohio State University, Columbus, OH
  • Andrew Fischer
    Neuroscience, Ohio State University, Columbus, OH
  • Footnotes
    Commercial Relationships Chris Zelinka, None; Melissa Scott, None; Andrew Fischer, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 5583. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Chris Zelinka, Melissa Scott, Andrew Fischer; Reactive microglia and the formation of Müller glia-derived retinal progenitors. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5583.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: Reactive microglia are prevalent in retinas where Müller glia have been stimulated to become proliferating progenitor-like cells. Thus, the purpose of this study was to investigate whether the activation or ablation of microglia influences the formation of Müller glia-derived progenitors in the chick retina in vivo. Further, we examine whether the activation or ablation of microglia influences the survival of neurons in damaged retinas.

Methods: Interleukin- 6 (IL6) and/or Fibroblast growth factor 2 (FGF2) were injected into the vitreous chamber of postnatal chicks. NMDA was used to elicit excitotoxic retinal damage. The combination of IL6 and clodronate-liposomes was used to ablate microglia. Immunocytochemistry was used to identify different types of reactive and proliferating glia. TUNEL was used to identify dying cells.

Results: IL6 stimulated the reactivity of microglia, which included the up-regulation of CD45 and lysosomal membrane glycoprotein, and acquisition of ameboid morphology. Activation of microglia with IL6 transiently protects retinal neurons from NMDA-induced damage and this effect was obviated when the microglia were ablated. The application of IL6 after NMDA-treatment caused widespread retinal folds and detachments, and these IL6-induced folds/detachments were completely prevented by the ablation of microglia. When the microglia were ablated, the formation of Müller glia-derived progenitors was greatly diminished in damaged retinas or in response to stimulation with the combination of insulin and FGF2. The combination of IL6 and FGF2 stimulated the formation of proliferating Müller glia-derived progenitors in the absence of retinal damage. The activation of microglia and ablation of microglia correlated with increases and decreases, respectively, in retinal levels of pro-inflammatory cytokines and Notch-signaling.

Conclusions: We conclude that reactive microglia profoundly influence the ability of Müller glia to become proliferating progenitor-like cells. We propose that activation of microglia with IL6, and accompanying increases in pro-inflammatory cytokines and Notch-signaling, enhances the ability of Müller glia to become progenitors.

Keywords: 699 retinal glia • 687 regeneration • 595 microglia  
×
×

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.

×