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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-2-12
pubmed:abstractText
Transgenic mice with vascular endothelial growth factor (VEGF) driven by the rhodopsin promoter (rho/VEGF mice) develop neovascularization that originates from the deep capillary bed of the retina and grows into the subretinal space. In rho/VEGF mice, VEGF expression in photoreceptors begins between postnatal days 5 and 7, the period when the deep capillary bed is developing. An important question is whether or not the developmental stage of the deep capillary bed is critical for occurrence of neovascularization. Also, although rho/VEGF mice are extremely useful for the study of ocular neovascularization, there are some applications for which the early onset of VEGF expression is a disadvantage. In this study, we used the reverse tetracycline transactivator (rtTA) inducible promoter system coupled to either the rhodopsin or interphotoreceptor retinoid-binding protein (IRBP) promoter to control the time of onset of VEGF transgene expression in photoreceptors. In the absence of doxycycline, adult double-transgenic rho/rtTA-TRE/VEGF or IRBP/rtTA-TRE/VEGF mice showed little VEGF transgene expression and no phenotype. The addition of doxycycline to the drinking water resulted in prominent transgene expression and evidence of neovascularization within 3 to 4 days. Like rho/VEGF mice, the neovascularization originated from the deep capillary bed of the retina, but it was more extensive and caused outer retinal folds followed by total retinal detachment. Real-time polymerase chain reaction and enzyme-linked immunosorbent assay demonstrated that the mice with inducible expression of VEGF that developed retinal detachment had much higher ocular levels of VEGF mRNA and protein compared to rho/VEGF mice that manifest a much milder phenotype. These data demonstrate that regardless of developmental stage of the vascular bed, increased expression of VEGF in the retina is sufficient to cause neovascularization, and high levels of expression cause severe neovascularization and traction retinal detachment. Mice with inducible expression of VEGF in the retina provide a valuable new model of ocular neovascularization.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/11839592-10362799, http://linkedlifedata.com/resource/pubmed/commentcorrection/11839592-10967078, http://linkedlifedata.com/resource/pubmed/commentcorrection/11839592-11095627, http://linkedlifedata.com/resource/pubmed/commentcorrection/11839592-11424092, http://linkedlifedata.com/resource/pubmed/commentcorrection/11839592-1279431, http://linkedlifedata.com/resource/pubmed/commentcorrection/11839592-1279432, http://linkedlifedata.com/resource/pubmed/commentcorrection/11839592-2440339, http://linkedlifedata.com/resource/pubmed/commentcorrection/11839592-7479819, http://linkedlifedata.com/resource/pubmed/commentcorrection/11839592-7521577, http://linkedlifedata.com/resource/pubmed/commentcorrection/11839592-7526212, http://linkedlifedata.com/resource/pubmed/commentcorrection/11839592-7540233, http://linkedlifedata.com/resource/pubmed/commentcorrection/11839592-7792603, http://linkedlifedata.com/resource/pubmed/commentcorrection/11839592-7846076, http://linkedlifedata.com/resource/pubmed/commentcorrection/11839592-7943121, http://linkedlifedata.com/resource/pubmed/commentcorrection/11839592-7980139, http://linkedlifedata.com/resource/pubmed/commentcorrection/11839592-8540853, http://linkedlifedata.com/resource/pubmed/commentcorrection/11839592-8643492, http://linkedlifedata.com/resource/pubmed/commentcorrection/11839592-8694732, http://linkedlifedata.com/resource/pubmed/commentcorrection/11839592-8942877, http://linkedlifedata.com/resource/pubmed/commentcorrection/11839592-9212753, http://linkedlifedata.com/resource/pubmed/commentcorrection/11839592-9227268, http://linkedlifedata.com/resource/pubmed/commentcorrection/11839592-9430560
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0002-9440
pubmed:author
pubmed:issnType
Print
pubmed:volume
160
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
711-9
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed-meshheading:11839592-Animals, pubmed-meshheading:11839592-Anti-Bacterial Agents, pubmed-meshheading:11839592-Doxycycline, pubmed-meshheading:11839592-Endothelial Growth Factors, pubmed-meshheading:11839592-Gene Expression Regulation, pubmed-meshheading:11839592-Humans, pubmed-meshheading:11839592-Lymphokines, pubmed-meshheading:11839592-Mice, pubmed-meshheading:11839592-Mice, Transgenic, pubmed-meshheading:11839592-Phenotype, pubmed-meshheading:11839592-Promoter Regions, Genetic, pubmed-meshheading:11839592-Recombinant Fusion Proteins, pubmed-meshheading:11839592-Retina, pubmed-meshheading:11839592-Retinal Detachment, pubmed-meshheading:11839592-Retinal Neovascularization, pubmed-meshheading:11839592-Rhodopsin, pubmed-meshheading:11839592-Statistics as Topic, pubmed-meshheading:11839592-Vascular Endothelial Growth Factor A, pubmed-meshheading:11839592-Vascular Endothelial Growth Factors
pubmed:year
2002
pubmed:articleTitle
Inducible expression of vascular endothelial growth factor in adult mice causes severe proliferative retinopathy and retinal detachment.
pubmed:affiliation
Department of Ophthalmology and Neuroscience, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287-9277, USA.
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