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Principal Investigator: NORMAN R HARRIS
Organization: LOUISIANA STATE UNIV HSC SHREVEPORT
Fiscal Year: 2023
Award: $365,000
Funding agency: National Eye Institute
Approximately 32-44% of the adult US population has hypertension, with one of the many complications
being hypertensive retinopathy. In one study, the prevalence of retinopathy was found to be 85% amongst
those with severe hypertension, and 25% for those with mild hypertension. Retinal consequences of
hypertension include arteriolar narrowing, hemorrhages, cotton wool spots (localized hypoxia), and optic
disk swelling. Other retinal changes include hyalinization of arteriolar walls, thickening of the vascular
basement membrane, closure of capillaries, smooth muscle degeneration, and blood-retinal barrier
dysfunction. Additionally, hypertension is a major risk factor for the highly threatening events of retinal artery
or vein occlusion. The primary treatment for hypertensive retinopathy is to reduce blood pressure; however,
consequences of the disease including narrowing of arterioles persist even following anti-hypertension
medication. Therefore, a better knowledge of the mechanisms of the disease could lead to the development
of additional and more effective therapeutic options. Our overall hypothesis is that the vascular
complications of hypertensive retinopathy are due phenotypic changes in endothelial and smooth muscle
cells, with vessel wall remodeling limiting recovery even with anti-hypertensive medication. The specific
aims are to: (1) determine the sex-dependent expression of the glycocalyx in the retina, and determine the
consequences of hypertension on this expression, (2) examine the sex-dependent expression of platelet
endothelial adhesion molecule-1 and vascular endothelial cadherin in the retina, and test the hypothesis
that changes in these junctional molecules in the hypertensive retina are due to endothelial-to-
mesenchymal transition, and (3) test the hypothesis that remodeling of blood vessel walls in the SHR retina
induces susceptibility to poor retinal perfusion when high blood pressure is reduced to normal.
Terms: <21+ years old><7B4 Antigen><7B4 protein><Address><Adhesions><Adult><Adult Human><AngII><Angiotensin II><Anti-Hypertensive Agents><Anti-Hypertensive Drugs><Anti-Hypertensives><Antihypertensive Agents><Antihypertensive Drugs><Antihypertensives><Area><BP reduction><Basement membrane><Bleeding><Blood Platelets><Blood Pressure><Blood Vessels><Blood capillaries><Blood flow><Blood leukocyte><Blood-Retinal Barrier><CD106><CD106 Antigens><CD144 Antigen><CD31 Antigens><CD62E Antigens><Cell Adhesion Molecule E-Selectin><Cell Coat><Cell-Extracellular Matrix><Chronic><Cold-Insoluble Globulins><Collagen><Collagen Peptidase><Collagen-Degrading Enzyme><Connexin 43><Connexin43><Cx43><Data><Dependence><Desmin><Development><Disease><Disorder><Drugs><Dysfunction><E-Selectin><ECM><EDN1><ELAM-1><ET-1><EndoCAM><Endothelial Adhesion Molecule 1><Endothelial Cells><Endothelial Leukocyte Adhesion Molecule-1><Endothelin Type 1><Endothelin-1><Endothelium><Event><Extracellular Matrix><Eye><Eyeball><FLK1><FN1><Female><Fibroblast-Specific Protein 1><Fibronectin 1><Fibronectins><Functional disorder><Future><Glycocalyx><Glycoproteins><Glypican><Gonadal Steroid Hormones><Health><Hemorrhage><Hypertension><Hypertensive Retinopathy><Hypotensive Agent><Hypotensive Drugs><Hypoxia><Hypoxic><INCAM-110><Inbred SHR Rats><Inbred WKY Rats><Inducible Cell Adhesion Molecule 110><Involuntary Muscle><KDR gene><Knowledge><LECAM-2><LETS Proteins><Large External Transformation-Sensitive Protein><Leanness><Leiomyocyte><Leukocyte Endothelial Cell Adhesion Molecule 2><Leukocytes><Leukocytes Reticuloendothelial System><Marrow leukocyte><Marrow platelet><Mediator><Medication><Mesenchymal><Microcirculation><Modeling><Molecular><N-Cadherin><Names><O element><O2 element><Opsonic Glycoprotein><Opsonic alpha(2)SB Glycoprotein><Optic Disk><Optic Nerve Head><Optic Papilla><Oxygen><Oxygen Deficiency><PECAM-1><Pathologic><Pathway interactions><Perfusion><Pharmaceutic Preparations><Pharmaceutical Preparations><Phenotype><Physiopathology><Platelet Endothelial Cell Adhesion Molecule><Platelet Endothelial Cell Adhesion Molecule-1><Platelet Glycoproteins><Platelets><Population><Predisposition><Prevalence><Proteoglycan><Recovery><Retina><Retinal Artery Occlusion><Retinal Blood Vessels><Retinal Diseases><Retinal Disorder><Retinal Vessels><Risk Factors><S100A4><S100A4 gene><SHR Rats><Sex Hormones><Sex Steroid Hormones><Sight><Skeletin><Smooth Muscle><Smooth Muscle Cells><Smooth Muscle Myocytes><Smooth Muscle Tissue Cell><Spontaneously Hypertensive Rats><Surface><Susceptibility><Swelling><Testing><Thinness><Thrombocytes><Thrombus><United States><VCAM><VCAM-1><VE-Cadherin><VEGF Receptors><VEGFR><VEGFR-2><VEGFR2><VPF Receptor><VWF receptor><Vascular Cell Adhesion Molecule><Vascular Cell Adhesion Molecule-1><Vascular Endothelial Cadherin><Vascular Endothelial Cadherin 1><Vascular Endothelial Cell Growth Factor Receptor><Vascular Endothelial Growth Factor Receptor 2><Vascular Hypertensive Disease><Vascular Hypertensive Disorder><Vascular Permeability Factor Receptor><Vasodilatation><Vasodilation><Vasorelaxation><Vimentin><Vision><Von Willebrand binding site><WKY Rats><White Blood Cells><White Cell><Wistar Kyoto Rats><Work><adulthood><alpha 2-Surface Binding Glycoprotein><anti-hypertension><arteriole><blood loss><blood pressure reduction><cadherin 5><capillary><collagenase><cotton wool spots><developmental><driving force><drug/agent><endothelial dysfunction><endothelial leukocyte adhesion molecule><experiment><experimental research><experimental study><experiments><gonadal steroids><high blood pressure><hyperpiesia><hyperpiesis><hypertensive><hypertensive disease><hypertensive disorder><lower BP><lower blood pressure><lowers blood pressure><male><membrane-organizing extension spike protein><migration><moesin><muscle degeneration><name><named><naming><negative affect><negative affectivity><normotensive><novel><optical disc><pathophysiology><pathway><pharmacologic><pressure><prevent><preventing><reduce BP><reduce blood pressure><reduction in BP><reduction in blood pressure><response><retina blood vessel structure><retina circulation><retina disease><retina disorder><retinal neuron><retinopathy><sex><sex steroid><spontaneous hypertensive rat><syndecan><therapeutically effective><vascular><vein occlusion><visual function><von Willebrand factor receptor><white blood cell><white blood corpuscle>