Preventing and reversing blindness: COMP-ANG1 and endothelial progenitor cells as a novel therapeutic approach in diabetic retinopathy

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Title Preventing and reversing blindness: COMP-ANG1 and endothelial progenitor cells as a novel therapeutic approach in diabetic retinopathy
Publication Type dissertation
School or College School of Medicine
Department Neurology
Author Cahoon, Judd Michael
Date 2015-08
Description Diabetes affects 25.8 million people in the United States and its prevalence is expected to triple in the next 20 years. Diabetic retinopathy (DR) affects nearly 30% of people with diabetes and is the leading cause of blindness in the working-age population. Current treatments for DR improve vision in only a minority of patients, and carry significant risks. This work advances a new approach that works by reversing retinal vascular damage and restoring normal perfusion to improve vision in this condition. Chapter 1 reviews the epidemiology, pathophysiology, and current standards of therapy for diabetic retinopathy. The roles of vascular maturation factor Angiopoietin-1 (Ang1) and its receptor Tie2 are introduced. Chapter 2 describes the development of an improved method for visualization of leukocytes in the diabetic mouse retina, which was critical for studies in this dissertation and broadly applicable to fields studying leukocyte endothelial interaction and inflammation. Chapter 3 focuses on the studies describing prevention of neurovascular dysfunction in diabetic retinopathy achieved by treating diabetic mice with gene therapy expressing COMP-Ang1. This chapter further details the studies performed to reverse diabetic retinopathy with a combination therapy consisting of endothelial colony-forming cells (ECFCs) and COMP-Ang1. We demonstrated that COMP-Ang1 enhanced the vasculogenic capabilities of ECFCs leading to increased integration into the diabetic retina and preservation of visual function in mice with advanced diabetic retinopathy. Chapter 4 represents my contributions toward the understanding of how targeting alternative VEGF receptor 2 splicing can suppress hemangiogenesis and lymphangiogenesis in the retina and choroid. This work was published in the FASEB journal in 2013. Chapter 5 describes my work published in PLoS ONE describing suppression of both tumor and ocular neovascularization, wherein we used morpholinos to increased soluble VEGF receptor 1. Chapter 6 concludes this work by recapping how the work accomplished in this dissertation built off of previous discoveries. The Appendix describes studies initiated to test the effects of COMP-Ang1 in an acute model of retinal ischemia, central retinal artery occlusion.
Type Text
Publisher University of Utah
Subject MESH Diabetic Retinopathy; Diabetes Mellitus; Retina; Angiopoietin-1; Receptor, TIE-2; Cadherins; Endothelial Progenitor Cells; Blindness; Vascular Endothelial Growth Factor A; Neovascularization, Pathologic; Angiogenesis Inhibitors; Cell- and Tissue-Based Therapy; Regional Blood Flow
Dissertation Institution University of Utah
Dissertation Name Doctor of Philosophy
Language eng
Relation is Version of Digital version of Preventing and Reversing Blindness: COMP-ANG1 and Endothelial Progenitor Cells as a Novel Therapeutic Approach in Diabetic Retinopathy
Rights Management Copyright © Judd Michael Cahoon 2015
Format application/pdf
Format Medium application/pdf
Format Extent 18,790,558 bytes
Source Original in Marriott Library Special Collections
ARK ark:/87278/s66x3vsg
Setname ir_etd
ID 1432962
Reference URL https://collections.lib.utah.edu/ark:/87278/s66x3vsg
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