Vascular Endothelial Growth Factor Is Sufficient to Produce Iris Neovascularization and Neovascular Glaucoma in a Nonhuman Primate

Tolentino, Michael J.; Miller, Joan W.; Gragoudas, Evangelos S.; Chatzistefanou, Klio; Ferrara, Napoleone; Adamis, Anthony P.

doi:10.1001/archopht.1996.01100140172010

Cited by 304 publications

(163 citation statements)

References 24 publications

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“…4 These vascular pathological findings are orchestrated by vascular endothelial growth factor (VEGF), a factor that potently promotes the growth and maintenance of endothelial cells and the formation of new vessels, and is implicated in both background and proliferative diabetic retinopathy. [5][6][7][8][9][10][11] Intraocular VEGF levels are increased in diabetic patients with blood-retinal barrier breakdown and neovascularization, 5,10,12,13 whereas the specific inhibition of VEGF prevents these complications in animal models. 7,11,14 Therefore, regulation of VEGF expression could conceivably be both a mediator for converging local and systemic stimuli modulating vessel pathophysiology, as well as a target for therapeutic intervention.…”

mentioning

confidence: 99%

Insulin-Like Growth Factor-I Plays a Pathogenetic Role in Diabetic Retinopathy

Poulaki

Joussen

Mitsiades

et al. 2004

The American Journal of Pathology

138

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Although the molecular pathophysiology of diabetic retinopathy, the current leading cause of blindness in Western societies, 1 is not fully elucidated, studies have documented a pivotal role for leukocyte adherence within the retinal vasculature. The adhesion of leukocytes to the retinal endothelium is a process that depends on ␤ 2 integrin-intercellular adhesion molecule (ICAM)-1 interactions and leads to breakdown of the blood-retinal barrier. 2 These data, in combination with our previous findings that aggressive anti-inflammatory therapy suppressed leukocyte adhesion and blood retinal breakdown in a relevant animal model, 3 support the hypothesis that a chronic subclinical inflammation may underlie much of the vascular pathology of diabetic retinopathy. 4 These vascular pathological findings are orchestrated by vascular endothelial growth factor (VEGF), a factor that potently promotes the growth and maintenance of endothelial cells and the formation of new vessels, and is implicated in both background and proliferative diabetic retinopathy. 5-11 Intraocular VEGF levels are increased in diabetic patients with blood-retinal barrier breakdown and neovascularization, 5,10,12,13 whereas the specific inhibition of VEGF prevents these complications in animal models. 7,11,14 Therefore, regulation of VEGF expression could conceivably be both a mediator for converging local and systemic stimuli modulating vessel pathophysiology, as well as a target for therapeutic intervention. Within a constellation of known modulators of VEGF expression that can possibly function at the transcriptional [through AP-1, AP-2, steroid hormone receptors, p53, and nuclear factor (NF-B)] or posttranscriptional level, [15][16][17][18] hypoxia is the most potent inducer of VEGF transcription in vivo; its effects are mainly mediated by the helix-loop helix (bHLH)-PAS transcription factor HIF-1␣, which heterodimerizes with the bHLH-PAS protein ARNT or HIF-1␤, 19 -22 and binds to consensus and ancillary hypoxia-response elements (HREs) in the VEGF promoter. 21,[23][24][25]

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mentioning

confidence: 99%

Insulin-Like Growth Factor-I Plays a Pathogenetic Role in Diabetic Retinopathy

Poulaki

Joussen

Mitsiades

et al. 2004

The American Journal of Pathology

138

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“…The retinas of patients with nonproliferative diabetic retinopathy or other retinal diseases may show elevated levels of VEGF without retinal neovascularization. 15,16 In primates, multiple intravitreous injections of VEGF result in iris neovascularization 17 and retinal vascular abnormalities including endothelial cell proliferation, 18 but do not cause definite retinal neovascularization. Similarly, intraocular implantation of pellets that provide sustained release of VEGF in primates fails to stimulate retinal neovascularization.…”

mentioning

confidence: 99%

Inducible Expression of Vascular Endothelial Growth Factor in Adult Mice Causes Severe Proliferative Retinopathy and Retinal Detachment

Ohno‐Matsui

Hirose

Yamamoto

et al. 2002

The American Journal of Pathology

158

157

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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 retinoidbinding protein ( Damage to retinal capillaries resulting in retinal ischemia is a constant feature in diseases complicated by retinal neovascularization. Therefore, the demonstration that vascular endothelial cell growth factor (VEGF) is up-regulated by hypoxia 1,2 focused attention on VEGF as a candidate mediator of retinal neovascularization. Circumstantial evidence suggesting that VEGF plays a role was provided by temporal and spatial correlation of VEGF expression with retinal neovascularization in patients and animal models. 3-8 Inhibition of retinal neovascularization by several different types of VEGF antagonists has demonstrated that VEGF is a necessary stimulatory factor. 9 -13

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“…Esses esforços permitiram estabelecer com clareza que os níveis de VEGF encontram-se elevados na neovascularização ocular (12)(13)(14) , que a elevação experimental dos níveis de VEGF induz a neovascularização ocular (15)(16) e que a inibição do VEGF pode impedir o desenvolvimento de neovasos (17)(18)(19) .…”

Section: Vegf-aunclassified

“…O VEGF tem propriedades neuroprotetoras já demonstradas, atribuídas em parte a sua capacidade de prolongar a sobrevida de cé-lulas endoteliais, neurônios e células de Schwann (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28) .…”

Section: Vegf-aunclassified

“…Uma única injeção intravítrea de VEGF em olhos de primatas leva à neovascularização iriana, retiniana e pré-retiniana (15,16,33) . Em outro estudo, observou-se que a razão VEGF 164 / VEGF 120 na retina de ratos com neovascularização retiniana induzida por isquemia era de 25.3 + 8.7, enFigura 1: A família de fatores de crescimento derivados do endotélio (VEGF) e seus receptores (VEGFR) encontrados nas células endoteliais vasculares e linfáticas; MMP9 = matrix metaloproteinase (9) Antiangiogênicos no glaucoma Rev Bras Oftalmol.…”

Section: Elevação Dos Níveis De Vegf Induz Neovascularização Ocularunclassified

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Antiangiogênicos no glaucoma

Lucena¹,

Yamane²

2008

Rev. bras.oftalmol.

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RESUMOA angiogênese é um processo complexo que resulta na formação de novos vasos sangüíneos. Ocorre tanto em situações fisiológicas quanto patológicas e está envolvida com várias patologias oculares. Dentre os mediadores químicos da angiogênese, o fator de crescimento do endotélio vascular (VEGF) é reconhecido como um dos mais importantes. Nos últimos anos, agentes antiVEGF foram introduzidos para o tratamento de neovascularizações do segmento posterior com resultados muito positivos. Alguns autores demonstraram benefícios do uso dessas substâncias no controle do glaucoma em situações específicas.

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Vascular Endothelial Growth Factor Is Sufficient to Produce Iris Neovascularization and Neovascular Glaucoma in a Nonhuman Primate

Cited by 304 publications

References 24 publications

Insulin-Like Growth Factor-I Plays a Pathogenetic Role in Diabetic Retinopathy

Insulin-Like Growth Factor-I Plays a Pathogenetic Role in Diabetic Retinopathy

Inducible Expression of Vascular Endothelial Growth Factor in Adult Mice Causes Severe Proliferative Retinopathy and Retinal Detachment

Antiangiogênicos no glaucoma

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