April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Recruitment and Activity of Dendritic Cells in Injured Retina was Strongly Inhibited in MyD88/Trif Deficient Mice
Author Affiliations & Notes
  • Dale S Gregerson
    Ophthalmology & Visual Neurosciences, University of Minnesota, Minneapolis, MN
  • Neal D Heuss
    Ophthalmology & Visual Neurosciences, University of Minnesota, Minneapolis, MN
  • Mark J Pierson
    Ophthalmology & Visual Neurosciences, University of Minnesota, Minneapolis, MN
  • Kim Montaniel
    Ophthalmology & Visual Neurosciences, University of Minnesota, Minneapolis, MN
  • Scott W McPherson
    Ophthalmology & Visual Neurosciences, University of Minnesota, Minneapolis, MN
  • Deborah A Ferrington
    Ophthalmology & Visual Neurosciences, University of Minnesota, Minneapolis, MN
  • Footnotes
    Commercial Relationships Dale Gregerson, None; Neal Heuss, None; Mark Pierson, None; Kim Montaniel, None; Scott McPherson, None; Deborah Ferrington, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 2193. doi:https://doi.org/
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      Dale S Gregerson, Neal D Heuss, Mark J Pierson, Kim Montaniel, Scott W McPherson, Deborah A Ferrington; Recruitment and Activity of Dendritic Cells in Injured Retina was Strongly Inhibited in MyD88/Trif Deficient Mice. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2193. doi: https://doi.org/.

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

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Abstract

Purpose: Microglia (MG) are studied by many labs, but there has been less effort devoted to other myeloid cells of the immune system in retina. We have observed close, physical contact between dendritic cells (DC) and retinal ganglion cells (RGC) and their axons following an optic nerve crush (ONC). Toll-like receptors (TLR) linked to NFkB by the MyD88 and Trif adaptor proteins are used by immune cells to sense their environment. We ask if they participate in this retinal injury response.

Methods: A unilateral ONC was used to provide an RGC injury. RGC were visualized by retrograde staining with Fluorogold or DiI (di-alkyl-indocarcarbocyanine) injected into the superior colliculus, or immunostaining RGC for B3-tubulin expression. DC were detected by their expression of green fluorescent protein (GFP) from the CD11c promoter, and deleted by treatment with diphtheria toxin (DTx) based on expression of the diphtheria toxin receptor (DTR) from the transgenic CD11c promoter. MG and recruited macrophages were visualized by their expression of CD11b and absence of both GFP and Ly6G. Fluorescence microscopy, flow cytometry, fundoscopy, and H&E stains were used to characterize the cells and their responses to the ONC. Multiple strains of transgenic and knockout mice were used.

Results: The earliest detection of GFP+ DC closely associated with RGC axons was at 3 days post-injury, with the frequency rising quickly after that. Following an ONC, the relative number of GFP+ DC in close contact with RGC and axons was greater than found for the MG. Recent GFP+ DC recruits to the ipsilateral retina following an ONC were the population most actively labeled by their scavenging of DiI-labeled RGC debris. This activity was severely compromised in MyD88/Trif double KO mice and to a lesser extent in MyD88 or Trif single KO mice. The MyD88/Trif dKO DC, which exhibit disruptions in NFkB signaling, were also less efficiently recruited into retina.

Conclusions: These results extend the influence of myeloid cells of the innate immune system in retina to include CD11b+ DC, previously shown to be substantially recruited from circulating progenitors, in addition to MG and macrophages. The altered recruitment and scavenging activity of cells from MyD88/Trif dKO mice suggests an important role for NFkB in the response to retinal injury.

Keywords: 595 microglia • 688 retina • 615 neuroprotection  
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