Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-3-9
pubmed:abstractText
Retinal vasculogenesis and ischemic retinopathies provide good model systems for study of vascular development and neovascularization (NV), respectively. Vascular endothelial cell growth factor (VEGF) has been implicated in the pathogenesis of retinal vasculogenesis and in the development of retinal NV in ischemic retinopathies. However, insulin-like growth factor-I and possibly other growth factors also participate in the development of retinal NV and intraocular injections of VEGF antagonists only partially inhibit retinal NV. One possible conclusion from these studies is that it is necessary to block other growth factors in addition to VEGF to achieve complete inhibition of retinal NV. We recently demonstrated that a partially selective kinase inhibitor, PKC412, that blocks phosphorylation by VEGF and platelet-derived growth factor (PDGF) receptors and several isoforms of protein kinase C (PKC), completely inhibits retinal NV. In this study, we have used three additional selective kinase inhibitors with different selectivity profiles to explore the signaling pathways involved in retinal NV. PTK787, a drug that blocks phosphorylation by VEGF and PDGF receptors, but not PKC, completely inhibited retinal NV in murine oxygen-induced ischemic retinopathy and partially inhibited retinal vascularization during development. CGP 57148 and CGP 53716, two drugs that block phosphorylation by PDGF receptors, but not VEGF receptors, had no significant effect on retinal NV. These data and our previously published study suggest that regardless of contributions by other growth factors, VEGF signaling plays a critical role in the pathogenesis of retinal NV. Inhibition of VEGF receptor kinase activity completely blocks retinal NV and is an excellent target for treatment of proliferative diabetic retinopathy and other ischemic retinopathies.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/10666398-10362799, http://linkedlifedata.com/resource/pubmed/commentcorrection/10666398-4835055, http://linkedlifedata.com/resource/pubmed/commentcorrection/10666398-7479819, http://linkedlifedata.com/resource/pubmed/commentcorrection/10666398-7489357, http://linkedlifedata.com/resource/pubmed/commentcorrection/10666398-7507904, http://linkedlifedata.com/resource/pubmed/commentcorrection/10666398-7521577, http://linkedlifedata.com/resource/pubmed/commentcorrection/10666398-7526212, http://linkedlifedata.com/resource/pubmed/commentcorrection/10666398-7540233, http://linkedlifedata.com/resource/pubmed/commentcorrection/10666398-7623107, http://linkedlifedata.com/resource/pubmed/commentcorrection/10666398-7708684, http://linkedlifedata.com/resource/pubmed/commentcorrection/10666398-7846076, http://linkedlifedata.com/resource/pubmed/commentcorrection/10666398-7943121, http://linkedlifedata.com/resource/pubmed/commentcorrection/10666398-7980139, http://linkedlifedata.com/resource/pubmed/commentcorrection/10666398-8449677, http://linkedlifedata.com/resource/pubmed/commentcorrection/10666398-8540853, http://linkedlifedata.com/resource/pubmed/commentcorrection/10666398-8616710, http://linkedlifedata.com/resource/pubmed/commentcorrection/10666398-8616716, http://linkedlifedata.com/resource/pubmed/commentcorrection/10666398-8643492, http://linkedlifedata.com/resource/pubmed/commentcorrection/10666398-8874387, http://linkedlifedata.com/resource/pubmed/commentcorrection/10666398-9212753, http://linkedlifedata.com/resource/pubmed/commentcorrection/10666398-9367346, http://linkedlifedata.com/resource/pubmed/commentcorrection/10666398-9430560
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Angiogenesis Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Endothelial Growth Factors, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Lymphokines, http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases, http://linkedlifedata.com/resource/pubmed/chemical/Phthalazines, http://linkedlifedata.com/resource/pubmed/chemical/Pyridines, http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Vascular Endothelial..., http://linkedlifedata.com/resource/pubmed/chemical/Rhodopsin, http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A, http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factors
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0002-9440
pubmed:author
pubmed:issnType
Print
pubmed:volume
156
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
697-707
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10666398-Aging, pubmed-meshheading:10666398-Angiogenesis Inhibitors, pubmed-meshheading:10666398-Animals, pubmed-meshheading:10666398-Animals, Newborn, pubmed-meshheading:10666398-Endothelial Growth Factors, pubmed-meshheading:10666398-Enzyme Inhibitors, pubmed-meshheading:10666398-Ischemia, pubmed-meshheading:10666398-Lymphokines, pubmed-meshheading:10666398-Mice, pubmed-meshheading:10666398-Mice, Inbred C57BL, pubmed-meshheading:10666398-Mice, Transgenic, pubmed-meshheading:10666398-Neovascularization, Pathologic, pubmed-meshheading:10666398-Phosphotransferases, pubmed-meshheading:10666398-Phthalazines, pubmed-meshheading:10666398-Pyridines, pubmed-meshheading:10666398-Receptor Protein-Tyrosine Kinases, pubmed-meshheading:10666398-Receptors, Growth Factor, pubmed-meshheading:10666398-Receptors, Vascular Endothelial Growth Factor, pubmed-meshheading:10666398-Retinal Vessels, pubmed-meshheading:10666398-Rhodopsin, pubmed-meshheading:10666398-Signal Transduction, pubmed-meshheading:10666398-Vascular Endothelial Growth Factor A, pubmed-meshheading:10666398-Vascular Endothelial Growth Factors
pubmed:year
2000
pubmed:articleTitle
Blockade of vascular endothelial cell growth factor receptor signaling is sufficient to completely prevent retinal neovascularization.
pubmed:affiliation
Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't