Mechanisms of Angiogenesis of Retinopathy of Prematurity

Summary

Principal Investigator: MARY ELIZABETH RUTH HARTNETT
Abstract: Oxygen fluctuations and increased inspired oxygen (hyperoxia) are risk factors for severe retinopathy of prematurity (ROP). Our hypothesis is that in vivo oxygen stresses, relevant to human severe ROP, increase avascular retina, which precedes and is a necessary prerequisite for the development of severe ROP. The increased avascular retina occurs through two different events: disordered angiogenesis and endothelial apoptosis. Specifically, oxygen fluctuations and relative tissue hypoxia upregulate Mueller cell VEGF and increases VEGF-VEGFR2 signaling in dividing endothelial cells (ECs) at the migrating front to disorient mitotic EC cleavage planes and interfere with normal retinal angiogenesis, thus increasing peripheral avascular retina. Furthermore oxygen fluctuations or hyperoxia cause different degrees of activation of NADPH oxidase to release reactive oxygen species that trigger apoptosis of ECs and endothelial precursor cells reducing retinal vascular development and increasing avascular retina, whereas supplemental oxygen in the setting of oxygen fluctuations will further activate NADPH oxidase to trigger signaling of cytoskeletal events to disorder cleavage plane orientation and interfere with normal angiogenesis. We will use oxygen induced retinopathy (OIR) models in rodents, which undergo retinal vascular development after birth. We will use either the genetically-manipulable mouse OIR model to study mechanisms of hyperoxia or relative tissue hypoxia, or the rat 50/10 OIR model in which the oxygen fluctuations mimic those experienced by preterm human infants that develop the more common form of severe ROP (zone II, stage 3 ROP). In Specific Aim 1, to test the prediction that increased VEGF signaling will disorient cleavage planes of dividing endothelial cells at the junction of vascular and avascular retina and interfere with intraretinal vascularization, we will silence Mueller cell derived VEGF164 in the rat 50/10 OIR using a microRNA to VEGFA or VEGF164 in an expression cassette packaged into a lentiviral vector. In Specific Aim 2, we will test the prediction that differential activation of NADPH oxidase triggers different signaling events leading to either apoptosis of endothelial cells or alteration of skeletal events and cleavage plane orientation in dividing endothelial cells. To do this we will use knockout mice to p47phox, a subunit of NADPH oxidase or pharmacologic inhibitors of NADPH oxidase. We will study the effects of EC-derived NADPH oxidase by depleting animals of macrophages. To change the degree of activation of NADPH oxidase, we will also use the 50/10 OIR model rescued in hyperoxia compared to the standard 50/10 OIR model rescued in room air. Methods include: confocal microscopy of retinal flat mounts to visualize endothelial cells at the junction of vascular and avascular retina to quantify apoptotic cells, capillary density, vascular and avascular retina, and to count the number of random mitotic planes of dividing phospho-histone stained endothelial cells;cryosections for phosphorylated VEGFR1 and 2, apoptosis (TUNEL, cleaved caspase-3) of co-labeled cells;laser capture microdissection;real-time-PCR to quantitate and in situ hybridization to detect location of mRNA of VEGF isoforms, VEGF receptors 1 and 2, neuropilins;ELISA and Western blot to measure protein (VEGF;cleaved caspase-3);immunoprecipitation and probing to detect phosphorylated VEGF receptors, protein kinase [unreadable]II, JAKs, STATs;construction of microRNAs to VEGFA or VEGF164 packaged into lentiviral vectors with a CD44 promoter;subretinal injections;systemic NADPH oxidase inhibitors or clodronate;measurement of reactive oxygen species (e.g., dihydroethidium);and NADPH oxidase activation.
Funding Period: 2003-12-01 - 2015-06-30
more information: NIH RePORT

Top Publications

  1. pmc Ophthalmologic findings in an 18-month-old boy with focal dermal hypoplasia
    Marielle P Young
    John A Moran Eye Center, University of Utah, Salt Lake City, Utah Electronic address
    J AAPOS 18:205-7. 2014
  2. pmc Anti-VEGF antibody leads to later atypical intravitreous neovascularization and activation of angiogenic pathways in a rat model of retinopathy of prematurity
    Manabu McCloskey
    Department of Ophthalmology, The John Moran Eye Center, University of Utah, Salt Lake City, UT 84132, USA
    Invest Ophthalmol Vis Sci 54:2020-6. 2013
  3. pmc Signaling pathways triggered by oxidative stress that mediate features of severe retinopathy of prematurity
    Haibo Wang
    John A Moran Eye Center, The University of Utah, Salt Lake City, UT 84132, USA
    JAMA Ophthalmol 131:80-5. 2013
  4. pmc Fluorescein angiography to estimate normal peripheral retinal nonperfusion in children
    Michael P Blair
    Retina Consultants, Des Plaines, IL 60016, USA
    J AAPOS 16:234-7. 2012
  5. pmc VEGF-mediated STAT3 activation inhibits retinal vascularization by down-regulating local erythropoietin expression
    Haibo Wang
    the John A Moran Eye Center, The University of Utah, Salt Lake City, Utah 84132, USA
    Am J Pathol 180:1243-53. 2012
  6. pmc Disruption of the association of integrin-associated protein (IAP) with tyrosine phosphatase non-receptor type substrate-1 (SHPS)-1 inhibits pathophysiological changes in retinal endothelial function in a rat model of diabetes
    L A Maile
    Departments of Medicine and Ophthalmology, School of Medicine, University of North Carolina at Chapel Hill, NC, USA
    Diabetologia 55:835-44. 2012
  7. pmc Upregulation of CCR3 by age-related stresses promotes choroidal endothelial cell migration via VEGF-dependent and -independent signaling
    Haibo Wang
    Department of Ophthalmology, The John Moran Eye Center, University of Utah, Salt Lake City, Utah, USA
    Invest Ophthalmol Vis Sci 52:8271-7. 2011
  8. pmc Soluble mediators of diabetic macular edema: the diagnostic role of aqueous VEGF and cytokine levels in diabetic macular edema
    Leah A Owen
    Department of Ophthalmology, Moran Eye Center, University of Utah, Salt Lake City, UT 84132, USA
    Curr Diab Rep 13:476-80. 2013
  9. pmc VEGFA activates erythropoietin receptor and enhances VEGFR2-mediated pathological angiogenesis
    Zhihong Yang
    The John Moran Eye Center, The University of Utah, Salt Lake City, Utah
    Am J Pathol 184:1230-9. 2014
  10. pmc Endothelial NADPH oxidase 4 mediates vascular endothelial growth factor receptor 2-induced intravitreal neovascularization in a rat model of retinopathy of prematurity
    Haibo Wang
    the John A Moran Eye Center, University of Utah, Salt Lake City, UT
    Mol Vis 20:231-41. 2014

Detail Information

Publications43

  1. pmc Ophthalmologic findings in an 18-month-old boy with focal dermal hypoplasia
    Marielle P Young
    John A Moran Eye Center, University of Utah, Salt Lake City, Utah Electronic address
    J AAPOS 18:205-7. 2014
    ..We describe the ophthalmologic findings in an 18-month-old boy with mosaicism of a novel mutation in PORCN. ..
  2. pmc Anti-VEGF antibody leads to later atypical intravitreous neovascularization and activation of angiogenic pathways in a rat model of retinopathy of prematurity
    Manabu McCloskey
    Department of Ophthalmology, The John Moran Eye Center, University of Utah, Salt Lake City, UT 84132, USA
    Invest Ophthalmol Vis Sci 54:2020-6. 2013
    ..We sought to understand causes of late-onset IVNV and AVA following anti-VEGF using an ROP model...
  3. pmc Signaling pathways triggered by oxidative stress that mediate features of severe retinopathy of prematurity
    Haibo Wang
    John A Moran Eye Center, The University of Utah, Salt Lake City, UT 84132, USA
    JAMA Ophthalmol 131:80-5. 2013
    ..In this study, we provide a current understanding of the role of oxidative stress in activating signaling pathways that cause pathologic features in severe retinopathy of prematurity as it manifests in the era of oxygen regulation...
  4. pmc Fluorescein angiography to estimate normal peripheral retinal nonperfusion in children
    Michael P Blair
    Retina Consultants, Des Plaines, IL 60016, USA
    J AAPOS 16:234-7. 2012
    ..To estimate the normal distance from vascular termini to ora serrata in children's eyes...
  5. pmc VEGF-mediated STAT3 activation inhibits retinal vascularization by down-regulating local erythropoietin expression
    Haibo Wang
    the John A Moran Eye Center, The University of Utah, Salt Lake City, Utah 84132, USA
    Am J Pathol 180:1243-53. 2012
    ..Our results suggest that rescuing Epo expression in the retina before the development of IVNV may promote normal developmental angiogenesis and, therefore, reduce the stimulus for later pathologic IVNV...
  6. pmc Disruption of the association of integrin-associated protein (IAP) with tyrosine phosphatase non-receptor type substrate-1 (SHPS)-1 inhibits pathophysiological changes in retinal endothelial function in a rat model of diabetes
    L A Maile
    Departments of Medicine and Ophthalmology, School of Medicine, University of North Carolina at Chapel Hill, NC, USA
    Diabetologia 55:835-44. 2012
    ....
  7. pmc Upregulation of CCR3 by age-related stresses promotes choroidal endothelial cell migration via VEGF-dependent and -independent signaling
    Haibo Wang
    Department of Ophthalmology, The John Moran Eye Center, University of Utah, Salt Lake City, Utah, USA
    Invest Ophthalmol Vis Sci 52:8271-7. 2011
    ....
  8. pmc Soluble mediators of diabetic macular edema: the diagnostic role of aqueous VEGF and cytokine levels in diabetic macular edema
    Leah A Owen
    Department of Ophthalmology, Moran Eye Center, University of Utah, Salt Lake City, UT 84132, USA
    Curr Diab Rep 13:476-80. 2013
    ..Further studies targeting individual cytokine activity will be important to our understanding of the pathogenesis and treatment. ..
  9. pmc VEGFA activates erythropoietin receptor and enhances VEGFR2-mediated pathological angiogenesis
    Zhihong Yang
    The John Moran Eye Center, The University of Utah, Salt Lake City, Utah
    Am J Pathol 184:1230-9. 2014
    ..Our results show that VEGFA-induced p-VEGFR2 activates EPOR and causes an interaction between p-EPOR and p-VEGFR2 to enhance VEGFA-induced EC proliferation by exacerbating STAT3 activation, leading to pathological angiogenesis...
  10. pmc Endothelial NADPH oxidase 4 mediates vascular endothelial growth factor receptor 2-induced intravitreal neovascularization in a rat model of retinopathy of prematurity
    Haibo Wang
    the John A Moran Eye Center, University of Utah, Salt Lake City, UT
    Mol Vis 20:231-41. 2014
    ..In this study, we tested the hypothesis that the isoform NOX4 in ECs contributed to vascular endothelial growth factor (VEGF)-induced angiogenesis and IVNV...
  11. pmc Quantitative analyses of retinal vascular area and density after different methods to reduce VEGF in a rat model of retinopathy of prematurity
    Haibo Wang
    Department of Ophthalmology, The John Moran Eye Center, University of Utah, Salt Lake City, Utah
    Invest Ophthalmol Vis Sci 55:737-44. 2014
    ..In this study, we compared the effects of these two approaches on retinal vascular development and capillary density in the inner and deep plexi in the rat ROP model...
  12. pmc Targeting Müller cell-derived VEGF164 to reduce intravitreal neovascularization in the rat model of retinopathy of prematurity
    YanChao Jiang
    Department of Ophthalmology, The John Moran Eye Center, University of Utah, Salt Lake City, Utah
    Invest Ophthalmol Vis Sci 55:824-31. 2014
    ..To determine whether knockdown of Müller cell-derived VEGFA-splice variant, VEGF164, which is upregulated in the rat retinopathy of prematurity (ROP) model, safely inhibits intravitreal neovascularization (IVNV)...
  13. pmc Activation of Rap1 inhibits NADPH oxidase-dependent ROS generation in retinal pigment epithelium and reduces choroidal neovascularization
    Haibo Wang
    1John A Moran Eye Center, University of Utah, 65 N Mario Capecchi Dr, Salt Lake City, UT 84132
    FASEB J 28:265-74. 2014
    ..These findings provide evidence that active Rap1 reduces CNV by interfering with the assembly of NADPH oxidase subunits and increasing the integrity of the RPE barrier...
  14. pmc Rap1 GTPase activation and barrier enhancement in rpe inhibits choroidal neovascularization in vivo
    Erika S Wittchen
    Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, North Carolina, United States of America
    PLoS ONE 8:e73070. 2013
    ....
  15. pmc Short hairpin RNA-mediated knockdown of VEGFA in Müller cells reduces intravitreal neovascularization in a rat model of retinopathy of prematurity
    Haibo Wang
    the John A Moran Eye Center, The University of Utah, Salt Lake City, Utah, USA
    Am J Pathol 183:964-74. 2013
    ..Our results suggest that targeted knockdown of overexpressed VEGFA in Müller cells safely reduces IVNV in a relevant ROP model...
  16. pmc Effects of oxygen on the development and severity of retinopathy of prematurity
    M Elizabeth Hartnett
    Moran Eye Center, University of Utah, Salt Lake City, UT 84132, USA
    J AAPOS 17:229-34. 2013
    ..This article reviews major studies on oxygen use in preterm infants and the effects on the development of ROP...
  17. pmc Expression of vascular endothelial growth factor and pigment epithelial-derived factor in a rat model of retinopathy of prematurity
    John S Hartmann
    University of North Carolina, Department of Ophthalmology, Chapel Hill, NC, USA
    Mol Vis 17:1577-87. 2011
    ..To determine the effects of oxygen fluctuations on pigment epithelial-derived factor (PEDF) and vascular endothelial growth factor (VEGF)/PEDF ratios in a relevant rat model of retinopathy of prematurity (ROP)...
  18. pmc Bone morphogenetic protein endothelial cell precursor-derived regulator regulates retinal angiogenesis in vivo in a mouse model of oxygen-induced retinopathy
    Isabel Moreno-Miralles
    McAllister Heart Institute, University of North Carolina at Chapel Hill, USA
    Arterioscler Thromb Vasc Biol 31:2216-22. 2011
    ..To assess the significance of BMP endothelial cell precursor-derived regulator (BMPER) in blood vessel formation in vivo, we investigated its role in retinal angiogenesis...
  19. pmc Predictive value of pre-plus disease in retinopathy of prematurity
    David K Wallace
    Duke University Eye Center, DUMC 3802, Durham, NC 27710, USA
    Arch Ophthalmol 129:591-6. 2011
    ..To investigate prospectively whether the presence of pre-plus disease predicts progression to severe retinopathy of prematurity (ROP) requiring laser treatment...
  20. pmc Activated NAD(P)H oxidase from supplemental oxygen induces neovascularization independent of VEGF in retinopathy of prematurity model
    Yuta Saito
    Department of Ophthalmology, Showa University, Tokyo, Japan
    Invest Ophthalmol Vis Sci 49:1591-8. 2008
    ..To study NAD(P)H oxidase-dependent outcomes after oxygen stresses that are similar to those experienced by preterm infants today using a rat model of retinopathy of prematurity...
  21. pmc Neutralizing VEGF decreases tortuosity and alters endothelial cell division orientation in arterioles and veins in a rat model of ROP: relevance to plus disease
    M Elizabeth Hartnett
    Department of Ophthalmology, The University of North Carolina, Chapel Hill, North Carolina, USA
    Invest Ophthalmol Vis Sci 49:3107-14. 2008
    ..To study the effects of vascular endothelial growth factor (VEGF) on endothelial nitric oxide synthetase (eNOS) and retinal vascular tortuosity and cleavage planes in a rat model of retinopathy of prematurity (ROP)...
  22. pmc Neutralizing antibody to VEGF reduces intravitreous neovascularization and may not interfere with ongoing intraretinal vascularization in a rat model of retinopathy of prematurity
    P Geisen
    Department of Ophthalmology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina
    Mol Vis 14:345-57. 2008
    ....
  23. ncbi CIB1 regulates endothelial cells and ischemia-induced pathological and adaptive angiogenesis
    Mohamed A Zayed
    Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Circ Res 101:1185-93. 2007
    ..These data therefore reveal a critical role for CIB1 in ischemia-induced pathological and adaptive angiogenesis...
  24. pmc Inhibition of NAD(P)H oxidase reduces apoptosis and avascular retina in an animal model of retinopathy of prematurity
    Yuta Saito
    Department of Ophthalmology, University of North Carolina, Chapel Hill, NC 27599 7041, USA
    Mol Vis 13:840-53. 2007
    ....
  25. pmc Orientation of endothelial cell division is regulated by VEGF signaling during blood vessel formation
    Gefei Zeng
    Department of Biology, University of North Carolina at Chapel Hill 27599, USA
    Blood 109:1345-52. 2007
    ....
  26. pmc Triamcinolone reduces neovascularization, capillary density and IGF-1 receptor phosphorylation in a model of oxygen-induced retinopathy
    M Elizabeth Hartnett
    Department of Ophthalmology, University of North Carolina, 6109A Neuroscience Research Building, Chapel Hill, NC 27599, USA
    Invest Ophthalmol Vis Sci 47:4975-82. 2006
    ..To study the effects of intravitreous triamcinolone acetonide (TA) on neovascularization (NV), capillary density, and retinal endothelial cell (REC) viability in a model of oxygen-induced retinopathy (OIR)...
  27. pmc Fibrovascular organization in the vitreous following laser for ROP: implications for prognosis
    M Elizabeth Hartnett
    Department of Ophthalmology, University of North Carolina, Chapel Hill, NC 27599 7040, USA
    Retina 26:S24-31. 2006
    ..To study associations between surgical outcome and mean postmenstrual age (PMA) when fibrovascular organization is detected between vascular and avascular retina following laser for acute retinopathy of prematurity (ROP)...
  28. pmc Chloride intracellular channel protein-4 functions in angiogenesis by supporting acidification of vacuoles along the intracellular tubulogenic pathway
    Barbara Ulmasov
    Department of Medicine, University of North Carolina, Chapel Hill, NC 27514 7155, USA
    Am J Pathol 174:1084-96. 2009
    ..We conclude that CLIC4 plays a critical role in angiogenesis by supporting acidification of vacuoles along the cell-hollowing tubulogenic pathway...
  29. pmc The role of supplemental oxygen and JAK/STAT signaling in intravitreous neovascularization in a ROP rat model
    Grace Byfield
    Department of Ophthalmology, University of North Carolina, Chapel Hill, North Carolina 27599 7041, USA
    Invest Ophthalmol Vis Sci 50:3360-5. 2009
    ....
  30. pmc Reduction in endothelial tip cell filopodia corresponds to reduced intravitreous but not intraretinal vascularization in a model of ROP
    Steven Budd
    Department of Ophthalmology, University of North Carolina Chapel Hill, 103 Mason Farm Road, CB 7041, 6135 NSRB, Chapel Hill, NC 27599, USA
    Exp Eye Res 89:718-27. 2009
    ..Reducing the number and length of filopodia/endothelial tip cell may reduce guidance cues for endothelial cells to migrate into the vitreous without interfering with migration into the retina toward a VEGF gradient...
  31. pmc Studies on the pathogenesis of avascular retina and neovascularization into the vitreous in peripheral severe retinopathy of prematurity (an american ophthalmological society thesis)
    Mary Elizabeth Hartnett
    Moran Eye Center, University of Utah, Salt Lake City, USA
    Trans Am Ophthalmol Soc 108:96-119. 2010
    ..To study vascular endothelial growth factor (VEGF) regulation in the development of intravitreous neovascularization and peripheral avascular retina in peripheral severe retinopathy of prematurity (ROP)...
  32. pmc The role of RPE cell-associated VEGF₁₈₉ in choroidal endothelial cell transmigration across the RPE
    Haibo Wang
    Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
    Invest Ophthalmol Vis Sci 52:570-8. 2011
    ..To determine the role of vascular endothelial growth factor 189 (VEGF₁₈₉) in choroidal endothelial cell (CEC) migration across the retinal pigment epithelium (RPE) and to explore the molecular mechanisms involved...
  33. pmc The role of vascular endothelial growth factor-induced activation of NADPH oxidase in choroidal endothelial cells and choroidal neovascularization
    Elizabeth Monaghan-Benson
    Department of Cell and Developmental Biology, University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, USA
    Am J Pathol 177:2091-102. 2010
    ..These steps may contributed to the pathology of neovascular age-related macular degeneration...
  34. pmc Association of retinal vascular endothelial growth factor with avascular retina in a rat model of retinopathy of prematurity
    Steven J Budd
    Department of Ophthalmology, University of North Carolina, Chapel Hill, USA
    Arch Ophthalmol 128:1014-21. 2010
    ..To study the effects of oxygen fluctuations on rat vascular endothelial growth factor (VEGF), VEGF receptor 1(VEGFR1), and VEGFR2 in a model of retinopathy of prematurity (ROP)...
  35. pmc New-onset maternal gestational hypertension and risk of retinopathy of prematurity
    Mohamed A Zayed
    Department of Ophthalmology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA
    Invest Ophthalmol Vis Sci 51:4983-8. 2010
    ..To evaluate associations between conditions of maternal new-onset gestational hypertension (mHTN) and the features imparting risk of severe retinopathy of prematurity (ROP) in preterm infants...
  36. pmc Increased angiogenic factors associated with peripheral avascular retina and intravitreous neovascularization: a model of retinopathy of prematurity
    Steven J Budd
    Department of Ophthalmology, School of Medicine, University of North Carolina, 130 Mason Farm Rd, Campus Box 7040, Chapel Hill, NC 27599 7040, USA
    Arch Ophthalmol 128:589-95. 2010
    ..To determine expression of vascular endothelial growth factor (VEGF), pigment epithelium-derived factor, and their respective receptors in retinas using a model of retinopathy of prematurity...
  37. pmc Aqueous vascular endothelial growth factor as a predictor of macular thickening following cataract surgery in patients with diabetes mellitus
    M Elizabeth Hartnett
    Department of Ophthalmology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Am J Ophthalmol 148:895-901.e1. 2009
    ....
  38. pmc The effects of oxygen stresses on the development of features of severe retinopathy of prematurity: knowledge from the 50/10 OIR model
    M Elizabeth Hartnett
    Department of Ophthalmology, University of North Carolina, 130 Mason Farm Road, Chapel Hill, NC 27599 7040, USA
    Doc Ophthalmol 120:25-39. 2010
    ..Increased signaling of VEGF appears important to the development of both avascular retina and intravitreous neovascularization...
  39. pmc Exogenous leukemia inhibitory factor (LIF) attenuates retinal vascularization reducing cell proliferation not apoptosis
    Janet R McColm
    Department of Ophthalmology, University of North Carolina, 6135 Neuroscience Research Building, 103 Mason Farm Road, Chapel Hill, NC 27599 7041, USA
    Exp Eye Res 83:438-46. 2006
    ..Antibody to LIF restored the cell counts to untreated levels. LIF reduced the number of cells in S phase. LIF attenuates retinal vascular development in vivo through growth arrest, and not apoptosis, of endothelial cells...

Research Grants30

  1. Indiana University Center for Pediatric Pharmacology
    Jamie L Renbarger; Fiscal Year: 2013
    ..The direct outcome of these studies will be new biomarkers and predictive signatures that will increase the precision of the existing dosing schemas used in the treatment of childhood cancer. ..
  2. Regulation and Function of the Matricellular Protein CCN1 in Ischemic Retinopathy
    Brahim Chaqour; Fiscal Year: 2013
    ..This proposal will provide new insights into the molecular mechanisms of CCN1 activities in vivo and may foster future safer, less destructive, and more effective therapies to harness ischemia-induced neovascularization in ROP. ..
  3. Synaptic Function: Effects of the Nerve Injury, Repair, and Altered Activity
    Timothy C Cope; Fiscal Year: 2013
    ..The Resume and Summary of Discussion above summarizes the final outcome of the group discussion. OVERALL PROGRAM EVALUATION ..
  4. Compound 49b prevents retinal endothelial cell apoptosis in type 2 diabetes
    Jena J Steinle; Fiscal Year: 2013
    ..This project focuses on a deeper understanding of the mechanisms underlying this protective action in a type II rat model, which will expedite movement of this novel drug into human clinical trials. ..
  5. NADPH Oxidase, Mitochondrial Dysfunction and Diabetic Retinopathy
    Renu A Kowluru; Fiscal Year: 2013
    ..abstract_text> ..
  6. Pathophysiology of Alveolar Epithelial Lung Injury
    Jacob I Sznajder; Fiscal Year: 2013
    ..The insights gained from the data generated from these studies will provide novel molecular targets for the development of new therapeutic strategies to treat patients with lung injury. ..
  7. Center for Gene Therapy of Cystic Firbosis
    John F Engelhardt; Fiscal Year: 2013
    ..These efforts have led to numerous basic and applied research findings that have enhanced the utility of gene therapies to both study and treat genetic diseases. ..
  8. Semi-volatile PCBs: Sources, Exposures, Toxicities
    Larry W Robertson; Fiscal Year: 2013
    ..These data and dietary studies in the last Aim will provide a scientific basis for risk assessment and advice for stakeholders with the ultimate goal to protect highly-exposed individuals and populations. ..
  9. Neurohumoral control of veins in hypertension
    Gregory D Fink; Fiscal Year: 2013
    ..This project tests the idea that altered structure or function of veins also may cause hypertension, and that it may be possible to treat hypertension using drugs that affect veins. ..
  10. Neuronal guidance molecules control revascularization in retinopathy
    Lois Smith; Fiscal Year: 2013
    ....
  11. The Biology of Prostate Cancer Skeletal Metastases
    EVAN TODD KELLER; Fiscal Year: 2013
    ..This combination of investigators, projects and cores result in a highly synergistic Program that will continue to provide cutting-edge research on PCa bone metastases. ..
  12. UNMC EPPLEY CANCER CENTER SUPPORT GRANT
    Kenneth H Cowan; Fiscal Year: 2013
    ....
  13. Elafin Therapy for Lung Diseases
    Marlene Rabinovitch; Fiscal Year: 2013
    ..The Administrative Core facilitates exchange of information and postdoctoral training in Lung Translational Medicine, and facilitates our strategy to move elafin into clinical trial in the next cycle. ..