July 2018
Volume 59, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2018
Pericytes promote capillary constriction leading to impaired retinal blood flow and microvascular dysfunction during ischemic damage.
Author Affiliations & Notes
  • Deborah Villafranca-Baughman
    Neuroscience, University of Montreal Hospital Research Center (CRCHUM), Montreal, Quebec, Canada
  • Luis Alarcon-Martinez
    Neuroscience, University of Montreal Hospital Research Center (CRCHUM), Montreal, Quebec, Canada
  • Adriana Di Polo
    Neuroscience, University of Montreal Hospital Research Center (CRCHUM), Montreal, Quebec, Canada
  • Footnotes
    Commercial Relationships   Deborah Villafranca-Baughman, None; Luis Alarcon-Martinez, None; Adriana Di Polo, None
  • Footnotes
    Support  Canadian Institutes of Health Research
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3732. doi:https://doi.org/
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      Deborah Villafranca-Baughman, Luis Alarcon-Martinez, Adriana Di Polo; Pericytes promote capillary constriction leading to impaired retinal blood flow and microvascular dysfunction during ischemic damage.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3732. doi: https://doi.org/.

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

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Abstract

Purpose : Microvascular deficits and reduced retinal blood flow are common features of conditions such as ischemic optic neuropathy and glaucoma. Pericytes, the contractile cells that wrap along the walls of capillaries, have been proposed to play a crucial role in the regulation of vascular blood flow. However, the role of pericytes in conditions characterized by pathological retinal hypoperfusion is currently unknown. Here, we used a mouse model of retinal ischemia and genetic tools to investigate the role of pericytes in microvascular alterations.

Methods : Ischemia was induced by ligation of the central retinal artery in transgenic mice carrying the pericyte-specific NG2 promoter driving red fluorescent protein (NG2:DsRed) or the genetically encoded calcium indicator GCaMP6 (NG2:GCaMP6). Changes in retinal capillary diameter and intracellular calcium in pericytes were examined at 1 hr after ischemia. First, ex vivo measurements of capillary diameter at pericyte locations were carried out using an unbiased stereological approach. Vessels and their associated pericytes were three-dimensionally reconstructed using IMARIS (Bitplane). Second, a novel and minimally invasive two-photon microscopy strategy was used for live imaging of microvasculature changes and calcium dynamics in retinal pericytes in vivo.

Results : We found a global reduction in capillary diameter in ischemic retinas relative to sham-operated controls (Ischemia: 4.7 ± 0.2 μm, Control: 5.2 ± 0.2 µm, Student’s t-test, p<0.001, n=4-6 mice/group). Analysis of capillary constrictions at pericyte locations showed an increase in the number of contracted microvessels in ischemic retinas relative to controls (Ischemia: 1,038 ± 277 constrictions, Sham-operated controls: 60 ± 36 constrictions, Student’s t-test, p<0.01, n=4-6 mice/group, 1374-1971 pericytes/group). Live imaging confirmed capillary constriction at the level of pericytes during ischemia, which correlated with robust intracellular calcium increase in pericytes (n=6-8/group).

Conclusions : Retinal pericytes react rapidly by undergoing marked increase in intracellular calcium and promoting capillary constriction, a response that leads to microvascular dysfunction. These findings suggest that pericyte-mediated capillary constriction might be a critical pathological event in patients with complete or partial decrease of retinal blood flow.

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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