July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Functional microglial involvement in the neurovascular unit
Author Affiliations & Notes
  • Michael Alexander Dixon
    University of Melbourne, Melbourne, Victoria, Australia
  • Andrew Ian Jobling
    University of Melbourne, Melbourne, Victoria, Australia
  • Joanna Phipps
    University of Melbourne, Melbourne, Victoria, Australia
  • Samuel Alexander Mills
    University of Melbourne, Melbourne, Victoria, Australia
  • Erica L Fletcher
    University of Melbourne, Melbourne, Victoria, Australia
  • Footnotes
    Commercial Relationships   Michael Dixon, None; Andrew Jobling, None; Joanna Phipps, None; Samuel Mills, None; Erica Fletcher, None
  • Footnotes
    Support  NHMRC grant APP1138509
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1640. doi:
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    • Get Citation

      Michael Alexander Dixon, Andrew Ian Jobling, Joanna Phipps, Samuel Alexander Mills, Erica L Fletcher; Functional microglial involvement in the neurovascular unit. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1640.

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

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Purpose : To investigate the physiological role of microglial communication with inner retinal vasculature and to explore the mechanism of vasoregulation.

Methods : Immunohistochemistry was used to characterise the extent of microglial contact with neurons and inner retinal vasculature (IB4) in Cx3cr1+/GFP and Cx3cr1GFP/GFP transgenic mice in which one or both copies of the chemokine receptor Cx3cr1 are replaced with green fluorescent protein (GFP). Live cell confocal imaging of Cx3cr1+/GFP retinal explants was used to assess process motility of microglia in close contact with superficial capillaries. Microglia-mediated capillary response was evaluated in Dark Agouti rat retinal explants by measuring capillary diameter at areas of microglial contact while perfusing fractalkine (200ng/ml), a neuronally derived chemokine and sole ligand for Cx3cr1, in the presence and absence of the Angiotensin II receptor antagonist, candesartan (.227μM).

Results : Results: Microglia make numerous physical connections with both blood vessels and synapses. The majority of inner retinal microglia in Cx3cr1+/GFP and Cx3cr1GFP/GFP retinae make contact with capillaries of the superficial vascular plexus (83 ± 1% versus 83 ± 1%, n=5, p>0.05). However, microglial density is increased in Cx3cr1GFP/GFP tissue (21 ± 3%, n=5, p<0.05). This results in an increase in the number of vessel-microglia contacts (19 ± 4%, n=5, p<0.05). Cx3cr1GFP/GFP microglia also display fewer branches per cell (-18 ± 4%, n=5, p<0.05) and accumulate in the subretinal space. Cx3cr1+ve cells making direct contact with inner retinal capillaries displayed no process motility over a duration of 20 mins (n=6 cells from 5 animals). Perfusing retinal explants with fractalkine evoked a constriction in capillaries that was reduced when explants were incubated with candesartan (-11 ± 3% baseline versus -2 ± 2% baseline, n=5-9, p<0.05).

Conclusions : Retinal microglia are involved in the neurovascular unit and regulate blood flow in response to fractalkine, a chemokine known to be released by neurons. Fractalkine-evoked capillary constriction is abolished in the presence of candesartan, suggesting angiotensin plays a role in microglia mediated vasoregulation.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.


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