Association of Retinal Vascular Endothelial Growth Factor With Avascular Retina in a Rat Model of Retinopathy of Prematurity

Budd, Steven; Thompson, Hilary W.; Hartnett, M. Elizabeth

doi:10.1001/archophthalmol.2010.158

Cited by 19 publications

(10 citation statements)

References 49 publications

(61 reference statements)

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“…As stated above, compared with the classic OIR models, 14,23 vessel abnormalities in our ligation model are rather mild. Considering the data from the classic retinal ischemia model, this result is not surprising.…”

Section: Discussionmentioning

confidence: 60%

“…20 Peripheral avascular regions appear most prominent at P14 and peripheral hypervascularization at P18. [21][22][23] The brain disorder PVL is caused by oxygen imbalances and ischemia and evokes motoric, visual, 24 and mental 25 disabilities in later life. 26,27 The disease is characterized by an increased sensitivity of immature oligodendrocytes to hypo-and hyperoxia, [28][29][30] which results in apoptosis of those developing brain cells.…”

mentioning

confidence: 99%

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Retinal Vessel Pathologies in a Rat Model of Periventricular Leukomalacia: A New Model for Retinopathy of Prematurity?

Steck

Blueml

Kampmann

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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Section: Discussionmentioning

confidence: 60%

mentioning

confidence: 99%

Retinal Vessel Pathologies in a Rat Model of Periventricular Leukomalacia: A New Model for Retinopathy of Prematurity?

Steck

Blueml

Kampmann

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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“…35 Repeated fluctuations in oxygen delivery in animal models leads to increased oxidative compounds, 36 over-expression of VEGF and VEGF receptor 2 and also over-activation of signaling cascades involving VEGFR2. 3,37 Besides fluctuations in oxygenation, risks for human ROP have included associations with poor infant growth 38 and increased oxidative stress. 39–41 …”

Section: Current Treatment For Rop and Reasons For Better Therapiesmentioning

confidence: 99%

Vascular Endothelial Growth Factor Antagonist Therapy for Retinopathy of Prematurity

Hartnett¹

2014

Clinics in Perinatology

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Synopsis In this article we discuss the growing problem of ROP worldwide, treatments for severe ROP including standard of care laser treatment, and the need for new treatments. We will also discuss the reasons to consider inhibiting the VEGF signaling pathway in severe ROP and the concerns about broad VEGF inhibition. Finally, we will cover the potential role of VEGF in ROP based on studies in animal models of oxygen-induced retinopathy (OIR), the effects of anti-VEGF based on basic research data, and the clinical relevance of these data.

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“…Therefore, NADPH oxidase activation and ROS-triggered signaling were studied, and it was found that hypoxia triggered NADPH oxidase activation in cultured ECs and induced angiogenesis in a model that fluctuated oxygen levels and led to an angiopathic retinopathy in vivo. 50 Retinal VEGF expression was increased in the model, 51 and both VEGF and NADPH oxidase appeared to trigger the Janus kinase/signal transducers and activators of transcription pathway and, specifically, STAT3 phosphorylation, which mediated aberrant angiogenesis. 52 Therefore, it was predicted that VEGF would activate NADPH oxidase in CECs.…”

Section: Discussionmentioning

confidence: 99%

Breaking barriers: insight into the pathogenesis of neovascular age-related macular degeneration

Wang¹,

Wittchen²,

Hartnett³

2011

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Neovascular age-related macular degeneration (AMD) is a leading cause of central visual acuity loss in a growing segment of the population, those over the age of 60 years. Treatment has improved over the last decade, with the availability of agents that inhibit the bioactivity of vascular endothelial growth factor (VEGF), but it is still limited, because of tachyphylaxis and potential risk and toxicity of anti-VEGF agents. The authors have sought to understand the mechanisms of choroidal endothelial cell (CEC) activation and transmigration of the retinal pigment epithelium (RPE) and of RPE barrier dysfunction, events preceding vision-threatening neovascular AMD. The authors developed physiologically relevant human RPE and CEC coculture and transmigration models that have been important in helping to understand causes of events in human neovascular AMD. The authors can control for interactions between these cells and can separately assess activation of signaling pathways in each cell type relevant during CEC transmigration. Using these models, it was found that VEGF, particularly the cell-associated VEGF splice variant VEGF189, accounts for about 40% of CEC transmigration across the RPE. This percentage is in the range of similar reports following clinical inhibition of VEGF in neovascular AMD. RPE VEGF189 working through CEC VEGF receptor 2 activates the small guanosine triphosphatase (GTPase) of the Rho family, Rac1, in CECs, which in turn facilitates CEC transmigration. Conversely, inhibition of Rac1 activity prevents CEC transmigration. Once activated, Rac1 aggregates with subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, resulting in the generation of reactive oxygen species. Activated NADPH oxidase increases choroidal neovascularization in animal models of laser-induced injury. Rac1 is also downstream of the eotaxin-CCR3 pathway, another pathway important in human neovascular AMD. Studies also suggest that active Ras-related protein 1 (Rap1), another small GTPase, in RPE can strengthen the RPE barrier integrity and can resist CEC transmigration of the RPE, suggesting Rap1 activation may be another potential target for preventing neovascular AMD.

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Association of Retinal Vascular Endothelial Growth Factor With Avascular Retina in a Rat Model of Retinopathy of Prematurity

Cited by 19 publications

References 49 publications

Retinal Vessel Pathologies in a Rat Model of Periventricular Leukomalacia: A New Model for Retinopathy of Prematurity?

Retinal Vessel Pathologies in a Rat Model of Periventricular Leukomalacia: A New Model for Retinopathy of Prematurity?

Vascular Endothelial Growth Factor Antagonist Therapy for Retinopathy of Prematurity

Breaking barriers: insight into the pathogenesis of neovascular age-related macular degeneration

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