Abstract:
:Diabetic retinopathy is a potentially blinding eye disease that threatens the vision of one-ninth of patients with diabetes. 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 was also 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 glucose; is rapidly reversed on a timescale of days; and is 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 observed no pericyte loss relative to nondiabetic 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.
journal_name
Diabetesjournal_title
Diabetesauthors
Corliss BA,Ray HC,Doty RW,Mathews C,Sheybani N,Fitzgerald K,Prince R,Kelly-Goss MR,Murfee WL,Chappell J,Owens GK,Yates PA,Peirce SMdoi
10.2337/db19-0471subject
Has Abstractpub_date
2020-07-01 00:00:00pages
1503-1517issue
7eissn
0012-1797issn
1939-327Xpii
db19-0471journal_volume
69pub_type
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