Pericyte Bridges in Homeostasis and Hyperglycemia

Diabetes. 2020 Jul;69(7):1503-1517. doi: 10.2337/db19-0471. Epub 2020 Apr 22.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / analysis
  • Becaplermin / physiology
  • Collagen Type IV / analysis
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetic Retinopathy / etiology*
  • Homeostasis*
  • Hyperglycemia / pathology*
  • Insulin / therapeutic use
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / physiology
  • Mice
  • Mice, Inbred C57BL
  • Myosin Heavy Chains / analysis
  • Pericytes / drug effects
  • Pericytes / physiology*
  • Platelet Endothelial Cell Adhesion Molecule-1 / analysis
  • Proteoglycans / analysis
  • Ribonuclease, Pancreatic / physiology
  • Streptozocin


  • Antigens
  • Collagen Type IV
  • Insulin
  • Klf4 protein, mouse
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • Pecam1 protein, mouse
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Proteoglycans
  • chondroitin sulfate proteoglycan 4
  • myosin 11, mouse
  • Becaplermin
  • Streptozocin
  • Ang2 protein, mouse
  • Ribonuclease, Pancreatic
  • Myosin Heavy Chains

Associated data

  • figshare/10.2337/figshare.12145425