June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Microglia appose the intermediate retinal vascular plexus and their ablation induces a decreased physiological and pathological intermediate plexus
Author Affiliations & Notes
  • Edith Aguilar
    Cell Biology, Scripps Research Institute, Del Mar, CA
  • Yoshihiko Usui
    Cell Biology, Scripps Research Institute, Del Mar, CA
  • Peter D Westenskow
    Cell Biology, Scripps Research Institute, Del Mar, CA
  • Toshihide Kurihara
    Cell Biology, Scripps Research Institute, Del Mar, CA
  • Elizabeth Scheppke
    Cell Biology, Scripps Research Institute, Del Mar, CA
  • Lindsay Keir
    Cell Biology, Scripps Research Institute, Del Mar, CA
  • Susumu Sakimoto
    Cell Biology, Scripps Research Institute, Del Mar, CA
  • Carli M Wittgrove
    Cell Biology, Scripps Research Institute, Del Mar, CA
  • Daniel Feitelberg
    Cell Biology, Scripps Research Institute, Del Mar, CA
  • Martin Friedlander
    Cell Biology, Scripps Research Institute, Del Mar, CA
  • Footnotes
    Commercial Relationships Edith Aguilar, None; Yoshihiko Usui, None; Peter Westenskow, None; Toshihide Kurihara, None; Elizabeth Scheppke, None; Lindsay Keir, None; Susumu Sakimoto, None; Carli Wittgrove, None; Daniel Feitelberg, None; Martin Friedlander, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 429. doi:
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      Edith Aguilar, Yoshihiko Usui, Peter D Westenskow, Toshihide Kurihara, Elizabeth Scheppke, Lindsay Keir, Susumu Sakimoto, Carli M Wittgrove, Daniel Feitelberg, Martin Friedlander; Microglia appose the intermediate retinal vascular plexus and their ablation induces a decreased physiological and pathological intermediate plexus. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):429.

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

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Abstract

Purpose: In humans and mice, the neurosensory retina contains three interconnecting vascular plexus layers. In mice these develop in early postnatal stages through mechanisms that are incompletely understood. We reported previously that amacrine cells interact with endothelial cells in the intermediate plexus and genetic ablation of amacrine cells and horizontal cells dramatically interfere with formation of the intraretinal vasculature (Usui Y et al. ARVO 2014). Since neurons and glia are known to function within neurovascular units to control blood supply, in this study we examined the potential contributions of microglia for angiogenesis using pharmacological approaches to deplete host myeloid progenitor cells.

Methods: Transgenic mice expressing Cre recombinase specifically in amacrine and horizontal cells (Ptf1a-Cre mice) were mated with floxed VHL or VEGF with cX3cR1GFP/+ mice to generate conditional knockouts. The CSF receptor tyrosine kinase inhibitor (Ki20227, 12.5 mg per kg of body weight) was subcutaneously administered daily to ptf1a-Cre; VHLf/f or VHLlf/f with cX3cR1GFP/+ mice. DMSO was used as a vehicle and control. Mice were sacrificed at different time points and branching points and retinal microglia distribution in the intermediate plexus are evaluated by whole mount preparation.<br />

Results: During normal vascular development, retinal microglia are present where the intermediate plexus will form at P12. At P18, concomitant with increases in vascular density, the number of microglia in the intermediate plexus of ptf1a-Cre; VHLf/f; cx3cr1GFP/+ mice was significantly increased compared with that in littermates controls, and a statistically significant correlation between the number of branching points of the intermediate plexus and number of microglia was observed in both groups. However, no difference existed between ptf1a-Cre; VEGFf/f; cx3cr1GFP/+ and VEGFf/f; cx3cr1GFP/+ mice in the number of microglia in the intermediate plexus at P15 and P18. Ki20227 was injected from P11-17, and a pronounced decrease in intermediate vascular density was observed in Ki20227-treated ptf1a-Cre; VHLf/f; cx3cr1GFP/+ and VHLf/f; cx3cr1GFP/+ mice compared with those of vehicle-treated mice.

Conclusions: These results suggest that amacrine neuron-microglia interactions are fundamental to the proper development of the intermediate retinal vascular plexus.

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