VEGF-induced choroidal damage in a murine model of retinal neovascularisation

Tee, Lisa; Penrose, Marissa A.; O'Shea, James; Lai, Chooi-May; Rakoczy, Elizabeth; Dunlop, Sarah

doi:10.1136/bjo.2007.130898

Cited by 18 publications

(17 citation statements)

References 20 publications

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“…14 In our earlier study, we sacrificed Kimba mice to examine, track, and localize changes in the fundus, retinal vasculature, and retinal morphology. 14,15,18,19 In these studies, we reported the existence of microaneurysm, venous dilatation, tortuosity, venous beading, and intraretinal microabnormalities in Kimba mice and we suggested that these features were similar to those observed in nonproliferative DR (NPDR) and RVO 20,21 in humans. Using the HRA+OCT imaging device, we not only confirmed the previous observations but for the first time we could follow the vascular, morphological, and retinal changes in real-time and within the same animal.…”

Section: Discussionmentioning

confidence: 59%

“…The results coincided with the previous histological work where the inner nuclear layer and outer retinal layers were thinner in comparison to control eyes. 18,19 The loss of cells in the inner retina of the Kimba mice is interesting, because although VEGF is not directly linked to photoreceptor loss, intraretinal and subretinal neovascularization have been associated with varying degrees of photoreceptor degeneration seen in macular telangiectasia and retinal angiomatous proliferation. 27,28 Although the blood vessels did not originate from the choroid but from the retinal vasculature in the Kimba mice, the process of photoreceptor loss observed in the Kimba mice is similar to wet AMD, whereby new fragile blood vessels grow into the photoreceptor outer segment layer and leak fluid and blood resulting in subsequent disintegration of the photoreceptor layer.…”

Section: Discussionmentioning

confidence: 99%

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In VivoMonitoring of VEGF-Induced Retinal Damage in the Kimba Mouse Model of Retinal Neovascularization

Rahman

Li²,

Lai³

et al. 2011

Current Eye Research

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In vivo monitoring of retinal vascular and neural retinal changes in the Kimba mice using the Spectralis HRA+OCT imaging device allowed us to assess and track VEGF-induced damages in great detail and in real-time. Real-time monitoring of these changes can be used to study the interplay between VEGF overexpression and other molecular factors and to monitor dynamic retinal changes following therapeutic intervention.

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

In VivoMonitoring of VEGF-Induced Retinal Damage in the Kimba Mouse Model of Retinal Neovascularization

Rahman

Li²,

Lai³

et al. 2011

Current Eye Research

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“…Comparable to DR patients, neovascularization in both mouse models is observed in the retina and not in the choroid [119,126]. Preretinal neovascularization, which is a well-known human characteristic of proliferative DR [129], is not present in the Akimba or the Kimba model, given that the formation of new blood vessels is directed toward the VEGF-overexpressing photoreceptors in the outer retina [119].…”

Section: Transgenic Akimba Mouse Modelmentioning

confidence: 89%

“…The heterozygous Akita male mice develop features similar to early pathophysiological changes of diabetic complications, but fail to exhibit the advanced stage vascular dysfunctions. The non-diabetic Kimba (trVEGF029) mouse model, in which photoreceptors transiently overexpress hVEGF, is characterized by several early and advanced DR-associated vascular changes such as vascular permeability, capillary non-perfusion, microaneurysms and retinal neovascularization [119,[122][123][124][125][126][127]. It has been reported that the combination of high blood glucose levels and VEGF overexpression exacerbates the vascular complications in the Akimba mouse eye [119,127].…”

Section: Transgenic Akimba Mouse Modelmentioning

confidence: 99%

Selection Strategy of In Vivo Models for Ophthalmic Drug Development in Diabetic Retinopathy

Geert¹,

Tjing-Tjing²

2016

J Mol Genet Med

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Diabetic Retinopathy (DR) is the most common microvascular complication of diabetes and is one of the leading causes of visual impairment worldwide. DR is a chronic eye disease that eventually can result in legal blindness due to the evolution towards the major vision-threatening disorders diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR). Current treatments with steroids, anti-VEGF compounds or retinal laser photocoagulation have shown a significant improvement in visual acuity in the advanced stage of the disease. However, main concerns are possible side effects and/or the relatively large number of clinical non-responders. A better understanding of the biological and molecular pathways not only in DR patients but also in the preclinical in vivo models would aid the development of novel and more efficient (personalized) therapeutic approaches for DR. This review aims to describe the pathways in a selection of diabetic, non-diabetic and surrogate rodent models of pathogenic neovascularization, vascular permeability, inflammation and neurodegeneration. None of these models can mimic the entire human pathophysiological progression but they all exhibit joint pathophysiological features with human DR pathogenesis. These combined features make these models very relevant in gaining a better understanding of the disease etiology and eventually improved strategies for drug screening. Through highlighting the most important biochemical and molecular pathways that these animal models have in common with DR patients, selection of the most suitable model for mechanistic studies and drug screening can be facilitated.

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“…The Akimba mouse was generated by crossing two mouse strains. The Kimba mice, a nondiabetic model of proliferative retinopathy resulting from overexpression of Vegf driven by the rhodopsin promoter [121,122], were crossed with the diabetic Ins2…”

Section: Mouse Genetic Models Of Drmentioning

confidence: 99%

Animal Models of Diabetic Retinopathy

Chen

Stitt

2015

Animal Models of Ophthalmic Diseases

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Purpose of Review Diabetic retinopathy (DR) is one of the most common complications associated with chronic hyperglycemia seen in patients with diabetes mellitus. While many facets of DR are still not fully understood, animal studies have contributed significantly to understanding the etiology and progression of human DR. This review provides a comprehensive discussion of the induced and genetic DR models in different species and the advantages and disadvantages of each model. Recent FindingsRodents are the most commonly used models, though dogs develop the most similar morphological retinal lesions as those seen in humans, and pigs and zebrafish have similar vasculature and retinal structures to humans. Nonhuman primates can also develop diabetes mellitus spontaneously or have focal lesions induced to simulate retinal neovascular disease observed in individuals with DR. Summary DR results in vascular changes and dysfunction of the neural, glial, and pancreatic β cells. Currently, no model completely recapitulates the full pathophysiology of neuronal and vascular changes that occur at each stage of diabetic retinopathy; however, each model recapitulates many of the disease phenotypes.

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VEGF-induced choroidal damage in a murine model of retinal neovascularisation

Abstract: We show that elevated retinal VEGF levels trigger pathophysiological changes in the choroid. We suggest that therapies to prevent vascular damage in diabetes must target both the retinal and choroidal vasculatures.

Cited by 18 publications

References 20 publications

In VivoMonitoring of VEGF-Induced Retinal Damage in the Kimba Mouse Model of Retinal Neovascularization

In VivoMonitoring of VEGF-Induced Retinal Damage in the Kimba Mouse Model of Retinal Neovascularization

Selection Strategy of In Vivo Models for Ophthalmic Drug Development in Diabetic Retinopathy

Animal Models of Diabetic Retinopathy

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