July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Microglial involvement in the neurovascular unit and alterations during early diabetic retinopathy
Author Affiliations & Notes
  • Andrew Ian Jobling
    Anatomy & Neuroscience, The University of Melbourne, Melbourne, Victoria, Australia
  • Samuel A Mills
    Anatomy & Neuroscience, The University of Melbourne, Melbourne, Victoria, Australia
  • Joanna Amy Phipps
    Anatomy & Neuroscience, The University of Melbourne, Melbourne, Victoria, Australia
  • Kirstan Anne Vessey
    Anatomy & Neuroscience, The University of Melbourne, Melbourne, Victoria, Australia
  • Michael A Dixon
    Anatomy & Neuroscience, The University of Melbourne, Melbourne, Victoria, Australia
  • Una Greferath
    Anatomy & Neuroscience, The University of Melbourne, Melbourne, Victoria, Australia
  • Bang V Bui
    Optometry and Vision sciences, The University of Melbourne, Melbourne, Victoria, Australia
  • Erica L Fletcher
    Anatomy & Neuroscience, The University of Melbourne, Melbourne, Victoria, Australia
  • Footnotes
    Commercial Relationships   Andrew Jobling, None; Samuel Mills, None; Joanna Phipps, None; Kirstan Vessey, None; Michael Dixon, None; Una Greferath, None; Bang Bui, None; Erica Fletcher, None
  • Footnotes
    Support  NH&MRC Australia #1138509, ARC DECRA #DE140100099
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5379. doi:
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      Andrew Ian Jobling, Samuel A Mills, Joanna Amy Phipps, Kirstan Anne Vessey, Michael A Dixon, Una Greferath, Bang V Bui, Erica L Fletcher; Microglial involvement in the neurovascular unit and alterations during early diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5379.

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

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Abstract

Purpose : To characterise the role of microglia in the neurovascular unit and vascular regulation within the inner retina and explore changes during early steptozotocin (STZ)-induced diabetes.

Methods : Immunohistochemistry was used to characterise the extent of microglial (anti-Iba1) contact with retinal synapses (anti-Vglut1) and the inner retinal vasculature (IB4). Transmission electron microscopy was used to detail the microglial-vascular association using the Cx3cr1GFP/+ transgenic animal where one copy of the microglial receptor, Cx3cr1 was replaced with enhanced green fluorescent protein. Capillary responses were quantified in retinal explants (Cx3cr1GFP/+mice and dark agouti rats) incubated in Ames and perfused with fractalkine (200ng/ml), the sole ligand for Cx3cr1. Diabetes was induced in dark agouti rats with a single intraperitoneal injection of STZ (55mg/kg) and animals taken after 4 weeks of hyperglycaemia.

Results : The majority of inner retinal microglia contact both neuronal synapses and capillaries (73 ± 8%), with half of these associated with the smallest vessels (< 8µm). At the ultrastructural level, microglial processes directly oppose pericytes and endothelial cells, wrapping around vessel lumen. Using fractalkine, the sole ligand to Cx3cr1, specific capillary constriction was observed in areas of microglial contact (-31 ± 8% of vehicle response, n = 6, p < 0.01), while no change in vascular diameter was evident in areas devoid of microglial contact. During early stages of STZ-induced diabetes there was increased microglial-vascular interaction (20 ± 8%, n > 10, p < 0.05) and capillary constriction (control, 9.5 ± 0.3 μm; STZ, 8.7 ± 0.3 μm, n = 12, p < 0.05). Ex vivo addition of fractalkine to diabetic retinae did not result in further capillary constriction (+4.0 ± 3%, n = 5, p > 0.05).

Conclusions : Retinal microglia form part of the neurovascular unit within the retina and are capable of vasoregulation. Changes in microglial regulation of the retinal vasculature early in diabetes may contribute to the progression of retinal pathology.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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