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Pericyte Bridges in Homeostasis and Hyperglycemia
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posted on 2020-05-14, 02:09 authored by Ada AdminAda Admin, Bruce A. Corliss, H. Clifton Ray, Richard W. Doty, Corbin Mathews, Natasha Sheybani, Kathleen Fitzgerald, Remi Prince, Molly Kelly-Goss, Walter L. Murfee, John Chappell, Gary Owens, Paul A. Yates, Shayn M. PeirceDiabetic retinopathy is a potentially blinding eye
disease that threatens the vision of a ninth of diabetic patients. Progression
of the disease has long been attributed to an initial dropout of pericytes that
enwrap the retinal microvasculature. Revealed through retinal vascular digests,
a subsequent increase in basement membrane bridges is observed. Using cell-specific
markers, we demonstrate that pericytes rather than endothelial cells colocalize
with these bridges. We show that the
density of bridges transiently increases with elevation of Ang-2, PDGF-BB, and
blood sugar, is rapidly reversed on a time scale of days, and often associated with
a pericyte cell body located off-vessel. Cell-specific knockout of KLF4 in
pericytes fully replicates this phenotype. In vivo imaging of limbal
vessels demonstrates pericyte migration off-vessel, with rapid pericyte
filopodial-like process formation between adjacent vessels. Accounting for off-vessel and on-vessel
pericytes, we observe no pericyte loss relative to non-diabetic control
retina. These findings reveal the
possibility that pericyte perturbations in location and process formation may
play a role in the development of pathological vascular remodeling in diabetic
retinopathy.