SPROUTING ANGIOGENESIS DURING RETINAL DEVELOPMENT AND WOUND HEALING Public Deposited

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  • March 21, 2019
Creator
  • Chong, Diana
    • Affiliation: School of Medicine, Curriculum in Genetics and Molecular Biology
Abstract
  • Endothelial cells, the cells that line blood vessels, become activated during development to sprout and form new vessels in a process termed angiogenesis. During development, sprouting angiogenesis is robust and is the main driving force behind vascularization of new tissues in the embryo. In contrast, endothelial cells are mainly quiescent in the adult and only become reactivated during physiological or pathological angiogenesis. The bone morphogenetic protein (BMP) pathway has been shown to be a pro-angiogenic cue. During postnatal retinal development, BMP receptors are expressed in the retinal vasculature and BMP ligands are expressed throughout the retina. Here, we show that deletion of BMP receptors, Alk1, Alk2, Alk3, and BMPR2 affect sprouting angiogenesis during development. Endothelial specific deletion of Alk2, Alk3, and BMPR2 resulted in decreased sprouting at the vascular front as well as branching in the vascular plexus, whereas deletion of Alk1 resulted in increased sprouting. These data point to a requirement of BMP signaling for proper patterning of the retinal vasculature during development. We also analyzed tortuous microvessels, abnormal vessels that arise during the wound healing process. Tortuous vessels are observed in many diseases, most notably cancer and diabetes. However, the causes and consequences of these abnormal vessels have not been elucidated. Here, we use intravital, high-resolution imaging to examine the formation, resolution, and sprouting of tortuous microvessels during wound healing. We found that tortuous microvessels are mainly located 100-300 μm from the wound center and that tortuous microvessels resolved by becoming normal again. Additionally, using fluorescent, microcarrier beads we found that beads became stuck in tortuous microvessels suggesting differences in flow. The shapes of endothelial cells within tortuous microvessels are round, indicative of activated cells, and exhibit sprout initiations at a higher frequency than normal vessels. Thus, we highlight an important, undiscovered feature of tortuous microvessels, sprouting, that can be used as a therapeutic target to normalize tortuous vessels during disease.
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  • In Copyright
Advisor
  • Conlon, Frank
  • Caron, Kathleen
  • Bautch, Victoria
  • Dayton, Paul
  • Rawls, John
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2017
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