RETINOPATHY OF PREMATURITY--UNDERSTAND ITS PATHOGENESIS

Summary

Principal Investigator: John Penn
Affiliation: Vanderbilt University
Country: USA
Abstract: The increased survival of premature infants in modem neonatal intensive care units has caused a resurgence of retinopathy of prematurity (ROP). It is reasoned that as more and smaller premature babies survive, the incidence of visual loss from ROP will continue to increase unless effective treatments are found. Advanced ROP is characterized by a period of unregulated growth of retinal blood vessels. This growth occurs by a process known as angiogenesis, indicating that the new vessels form by an abnormal sprouting of existing vessels. The loss of vision from angiogenesis is not unique to ROP; collectively, ocular disorders with this feature constitute the leading cause of blindness in the U.S. The significance of research aimed at understanding retinal angiogenesis in an animal model of one of these diseases is amplified by the potential of applying the new knowledge to other ocular conditions in which angiogenesis plays a role. The ultimate goal of this project is to develop methods to prevent retinal angiogenesis based upon understanding gained from studies of a rat model of ROP. To this end, four interrelated research projects are proposed: 1) identification of components of the endothelial cell signal pathways by which angiogenesis is initiated, 2) examination of the digestion of extracellular matrix by angiogenic endothelial cells, 3) investigation of the cell attachment mechanisms by which angiogenic endothelial cells migrate, and 4) determination of the precise mechanism through which fluctuating oxygen exposures encourage retinal angiogenesis.
Funding Period: 1988-04-01 - 2001-06-30
more information: NIH RePORT

Top Publications

  1. pmc The role of the NFAT signaling pathway in retinal neovascularization
    Colin A Bretz
    Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee
    Invest Ophthalmol Vis Sci 54:7020-7. 2013
  2. doi Imaging of endothelial progenitor cell subpopulations in angiogenesis using quantum dot nanocrystals
    Joshua M Barnett
    Vanderbilt Eye Institute, Vanderbilt University, Nashville, TN, USA
    Methods Mol Biol 1026:45-56. 2013
  3. pmc Peroxisome proliferator-activated receptor-β/δ regulates angiogenic cell behaviors and oxygen-induced retinopathy
    Megan E Capozzi
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
    Invest Ophthalmol Vis Sci 54:4197-207. 2013
  4. pmc Ketorolac inhibits choroidal neovascularization by suppression of retinal VEGF
    Stephen J Kim
    Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
    Exp Eye Res 91:537-43. 2010
  5. pmc Genetic deletion of COX-2 diminishes VEGF production in mouse retinal Müller cells
    Susan E Yanni
    Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232 8808, USA
    Exp Eye Res 91:34-41. 2010
  6. pmc The effects of nepafenac and amfenac on retinal angiogenesis
    Susan E Yanni
    Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, 8000 Medical Center East, Nashville, TN 37232 8808, USA
    Brain Res Bull 81:310-9. 2010
  7. pmc The development of the rat model of retinopathy of prematurity
    Joshua M Barnett
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA
    Doc Ophthalmol 120:3-12. 2010
  8. pmc Reduced choroidal neovascular membrane formation in cyclooxygenase-2 null mice
    Kasra A Rezaei
    Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Invest Ophthalmol Vis Sci 52:701-7. 2011
  9. pmc Proteomic analysis of the retina: removal of RPE alters outer segment assembly and retinal protein expression
    Xiaofei Wang
    Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
    Glia 57:380-92. 2009
  10. pmc Pharmacologic and genetic manipulation of MMP-2 and -9 affects retinal neovascularization in rodent models of OIR
    Joshua M Barnett
    Vanderbilt Eye Institute, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Invest Ophthalmol Vis Sci 48:907-15. 2007

Detail Information

Publications10

  1. pmc The role of the NFAT signaling pathway in retinal neovascularization
    Colin A Bretz
    Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee
    Invest Ophthalmol Vis Sci 54:7020-7. 2013
    ....
  2. doi Imaging of endothelial progenitor cell subpopulations in angiogenesis using quantum dot nanocrystals
    Joshua M Barnett
    Vanderbilt Eye Institute, Vanderbilt University, Nashville, TN, USA
    Methods Mol Biol 1026:45-56. 2013
    ....
  3. pmc Peroxisome proliferator-activated receptor-β/δ regulates angiogenic cell behaviors and oxygen-induced retinopathy
    Megan E Capozzi
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
    Invest Ophthalmol Vis Sci 54:4197-207. 2013
    ....
  4. pmc Ketorolac inhibits choroidal neovascularization by suppression of retinal VEGF
    Stephen J Kim
    Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
    Exp Eye Res 91:537-43. 2010
    ..05) and 29% at 7 days (P<0.001) and retinal VEGF by 31% at 3 days (P=0.10) and 19% at 7 days (P<0.001). Topical ketorolac inhibited CNV and suppressed retinal PGE(2) and VEGF production...
  5. pmc Genetic deletion of COX-2 diminishes VEGF production in mouse retinal Müller cells
    Susan E Yanni
    Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232 8808, USA
    Exp Eye Res 91:34-41. 2010
    ..Our study suggests that PGE(2), signaling through the EP(2) and/or EP(4) receptor and PKA, mediates the VEGF response of Müller cells...
  6. pmc The effects of nepafenac and amfenac on retinal angiogenesis
    Susan E Yanni
    Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, 8000 Medical Center East, Nashville, TN 37232 8808, USA
    Brain Res Bull 81:310-9. 2010
    ..The purpose of the present study was to investigate the capacity of amfenac to inhibit discrete aspects of the angiogenic cascade in vitro, and to test the efficacy of amfenac and nepafenac in vivo, using the rat OIR model...
  7. pmc The development of the rat model of retinopathy of prematurity
    Joshua M Barnett
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA
    Doc Ophthalmol 120:3-12. 2010
    ..This article provides historical perspective on the development and use of the rat model of ROP. Key findings generated through the use of this model are also summarized...
  8. pmc Reduced choroidal neovascular membrane formation in cyclooxygenase-2 null mice
    Kasra A Rezaei
    Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Invest Ophthalmol Vis Sci 52:701-7. 2011
    ....
  9. pmc Proteomic analysis of the retina: removal of RPE alters outer segment assembly and retinal protein expression
    Xiaofei Wang
    Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
    Glia 57:380-92. 2009
    ....
  10. pmc Pharmacologic and genetic manipulation of MMP-2 and -9 affects retinal neovascularization in rodent models of OIR
    Joshua M Barnett
    Vanderbilt Eye Institute, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Invest Ophthalmol Vis Sci 48:907-15. 2007
    ..The susceptibilities of MMP-2(-/-) and -9(-/-) mice to preretinal neovascularization were investigated in a mouse model of oxygen-induced retinopathy...