Transdifferentiated Retinal Pigment Epithelial Cells are Immunoreactive for Vascular Endothelial Growth Factor in Surgically Excised AgeRelated Macular Degeneration-Related Choroidal Neovascular Membranes.

Lopez, Pedro F.; Sippy, Brian D.; Lambert, H. M.; Thach, Allen B.; Hinton, David R.

doi:10.1097/00006982-199805000-00035

Cited by 330 publications

(434 citation statements)

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“…VEGF is found in RPE in surgically excised human AMD specimens of CNV (Lopez et al, 1996;Frank et al, 1996;Grossniklaus et al, 2002). VEGF has been localized to CNV in rodent models of laserinduced CNV (Bora et al, 2005;Yi et al, 1997) and genetically modified mouse models of CNV (Ambati et al, 2003).…”

Section: Vegf In Pathologic Neovascularization: Models Of Neovascularmentioning

confidence: 99%

“…There is mounting evidence that increased VEGF expression is associated with and causes pathologic neovascularization in AMD and in animal models of AMD (Lopez et al, 1996;Frank et al, 1996;Yi et al, 1997;Baffi et al, 2000;Schwesinger et al, 2001;Grossniklaus et al, 2002;Ishida et al, 2003;Wang et al, 2003). VEGF is found in RPE in surgically excised human AMD specimens of CNV (Lopez et al, 1996;Frank et al, 1996;Grossniklaus et al, 2002).…”

Section: Vegf In Pathologic Neovascularization: Models Of Neovascularmentioning

confidence: 99%

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Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

636

527

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Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the U.S., for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40 kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis.

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Section: Vegf In Pathologic Neovascularization: Models Of Neovascularmentioning

confidence: 99%

Section: Vegf In Pathologic Neovascularization: Models Of Neovascularmentioning

confidence: 99%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

636

527

View full text Add to dashboard Cite

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“…36 Age-related macular degeneration risk factors, like those of coronary artery disease, include smoking, systemic arterial hypertension, and hyperlipidemia, as well as mutations in several immunomodulatory proteins, including complement factor H. 37 Focal ischemia of the outer retina along with inflammation induces the growth of neovascular membranes from the choriocapillaris into either the sub-retinal pigment epithelium or subphotoreceptor space, which when complicated by transudation and bleeding, causes moderate to severe dysfunction of the photoreceptor-retinal pigment epithelium-choriocapillaris complex. 38,39 Several factors, including VEGF detection within neovascular membranes, 40 the high incidence of blindness due to exudative AMD, and aging of the population, have made AMD the primary driver of ocular anti-VEGF drug development. Pegaptanib, an aptamer to VEGF 165 , became the first available ophthalmic anti-VEGF agent in 2004.…”

Section: Ocular Conditions and Therapiesmentioning

confidence: 99%

The Expanding Role of Vascular Endothelial Growth Factor Inhibitors in Ophthalmology

Stewart

2012

Mayo Clinic Proceedings

167

105

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Vascular endothelial growth factor (VEGF) plays an important role in both physiologic and pathologic angiogenesis and contributes to increased permeability across both the blood-retinal and blood-brain barriers. After 2 decades of extensive research into the VEGF families and receptors, specific molecules have been targeted for drug development, and several medications have received US Food and Drug Administration approval. Bevacizumab, a full-length antibody against VEGF approved for the intravenous treatment of advanced carcinomas, has been used extensively in ophthalmology for exudative age-related macular degeneration, diabetic retinopathy, retinal vein occlusions, retinopathy of prematurity, and other chorioretinal vascular disorders. Pegaptanib and ranibizumab have been developed specifically for intraocular use, whereas the soon-to-be-introduced aflibercept (VEGF Trap-Eye) is moving through clinical trials for both intraocular and systemic use. Although these drugs exhibit excellent safety profiles, ocular and systemic complications, particularly thromboembolic events, remain a concern in patients receiving therapy. Patients experiencing adverse events that may be related to VEGF suppression should be carefully evaluated by both the ophthalmologist and the medical physician to reassess the need for intraocular therapy and explore the feasibility of changing medications. For this review a search of PubMed from January 1, 1985 through April 15, 2011, was performed using the following terms (or combination of terms): vascular endothelial growth factors, VEGF, age-related macular degeneration, diabetic retinopathy, retina vein occlusions, retinopathy of prematurity, intravitreal injections, bevacizumab, ranibizumab, and VEGF Trap. Studies were limited to those published in English. Other articles were identified from bibliographies of retrieved articles and archives of the author.

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“…14 Clinical studies have shown that the age-related changes in Bruch's membrane and the dropout of choriocapillaris cause impaired diffusion of oxygen. 15,16 Outer retina hypoxia 17 and the resulting transcriptional activation of the HIF-1 [18][19][20] may become an important driving force of CNV formation by stimulating VEGF overexpression, 21,22 in addition to the effects of increased oxidative stress and low-grade inflammation. Recently, it has also been shown that CNV membranes are positive for HIF-1 expression, and this expression tends to be localized to the retinal pigment epithelium (RPE) cells.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory efficacy of hypoxia-inducible factor 1α short hairpin RNA plasmid DNA-loaded poly (D, L-lactide-co-glycolide) nanoparticles on choroidal neovascularization in a laser-induced rat model

Zhang

et al. 2009

Gene Ther

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The aim of this study was to evaluate the possibility of poly (D, L-lactide-co-glycolide) nanoparticle (NPs) as a gene vector for functional plasmid DNA (pDNA) and to investigate its inhibitory efficacy on experimental choroidal neovascularization (CNV). We developed intravitreal administered, hypoxia-inducible factor 1a (HIF-1a) short hairpin RNA and green fluorescent protein (GFP) co-expressed pDNA-loaded NPs (pshHIF-1a NPs). CNV was induced by laser photocoagulation in 112 rats. The rats were then randomly assigned to be injected intravitreally with phosphate-buffered saline (PBS), blank NPs, naked pDNA, control pDNA NPs and pshHIF-1a NPs, respectively, and non-injection group was set as the control. Immunofluorescence staining, fluorescein fundus angiography and histologic analysis were performed to evaluate the inhibitory efficacy on CNV. The results showed that the expression of GFP preferentially localized in the retinal pigment epithelium cell layer and lasted for 4 weeks. The fluorescein leakage areas of CNV were significantly larger in the PBS, blank NPs, control pDNA NPs, non-injection group and naked pDNA group than in pshHIF-1a NPs group (Po0.01). The mean thickness of the CNV lesions in the intravitreally pshHIF1a NPs-treated group was significantly smaller than other groups (Po0.01). No signs of functional or ultrastructural destruction in retina were detected. Therefore, pshHIF-1a NPs may act as a novel therapeutic option to transfer specific pDNA and inhibit the formation of experimental CNV.

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Transdifferentiated Retinal Pigment Epithelial Cells are Immunoreactive for Vascular Endothelial Growth Factor in Surgically Excised AgeRelated Macular Degeneration-Related Choroidal Neovascular Membranes.

Cited by 330 publications

References 0 publications

Vascular endothelial growth factor in eye disease

Vascular endothelial growth factor in eye disease

The Expanding Role of Vascular Endothelial Growth Factor Inhibitors in Ophthalmology

Inhibitory efficacy of hypoxia-inducible factor 1α short hairpin RNA plasmid DNA-loaded poly (D, L-lactide-co-glycolide) nanoparticles on choroidal neovascularization in a laser-induced rat model

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