Pericyte Bridges in Homeostasis and Hyperglycemia
figureposted on 14.05.2020 by Ada 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. Peirce
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Diabetic 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.