Open AccessFractalkine-induced microglial vasoregulation occurs within the retina and is altered early in diabetic retinopathy
Author(s) -
Samuel A. Mills,
Andrew I Jobling,
Michael Dixon,
Bang V. Bui,
Kirstan A. Vessey,
John Phipps,
Ursula Greferath,
Gene Venables,
Vickie Wong,
Connie Hoi Yee Wong,
Zheng He,
Flora Hui,
James C Young,
Josh Tonc,
Elena Ivanova,
Botir T. Sagdullaev,
Erica L. Fletcher
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2112561118
Subject(s) - microglia , retina , cx3cr1 , biology , retinal , neuroscience , endocrinology , microbiology and biotechnology , medicine , inflammation , immunology , chemokine , chemokine receptor , biochemistry
Significance This work identifies a role for microglia, the innate immune cells of the CNS, in the local control of the retinal vasculature and identifies deficits early in diabetes. Microglia contact neurons and vasculature and express several vasoactive agents. Activation of microglial fractalkine-Cx3cr1 signaling leads to capillary constriction and blocking the renin-angiotensin system (RAS) with candesartan abolishes microglial-mediated vasoconstriction in the retina. In early diabetes, reduced retinal blood flow is coincident with capillary constriction, increased microglial–vessel association, loss of microglial–capillary regulation, and altered microglial expression of the RAS pathway. While candesartan restores retinal capillary diameter early in diabetes, targeting of microglial–vascular regulation is required to prevent coincident dilation of large retinal vessels and reduced retinal blood flow.