A new kind of labyrinth-like capillary is responsible for leakage from human choroidal neovascular endothelium, as investigated by high-resolution electron microscopy

Schraermeyer, Ulrich; Julien, Sylvie; Biesemeier, Antje; Bartz‐Schmidt, Karl Ulrich; Wolburg, Hartwig

doi:10.1007/s00417-014-2733-0

Cited by 5 publications

(8 citation statements)

References 32 publications

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“…Few fenestrations in the endothelium were observed in the CNV vessels of this CNV rat model ( Fig. 4 3E), which correlates with the low number of endothelial fenestrations in human CNV (Biesemeier et al, 2014, Schraermeyer et al, 2015. Hofman's group indicated that the vessel leakage was not caused by the fenestration formation, but was due to the increased active pinocytotic vesicles in the endothelia of CNV vessels (Hofman et al, 2000).…”

Section: Overexpression Of Vegf Leads To the Hyperpermeability Of Thesupporting

confidence: 52%

“…Multi-layered basement membranes were often observed around the CNV vessels ( Fig. 4D), which is also a feature of human CNV (Schraermeyer et al, 2015).…”

Section: As Shown In Figs 3 4 the Cnv Induced By Vegf Overexpressiomentioning

confidence: 74%

“…4B). The endothelium of the CNV vessels (Schraermeyer et al, 2015). Multi-layered basement membranes were often observed around the CNV vessels ( Fig.…”

Section: As Shown In Figs 3 4 the Cnv Induced By Vegf Overexpressiomentioning

confidence: 98%

“…Five human CNV samples removed during sub-macular surgery were analyzed by LM/EM and IHC (the same samples used in (Biesemeier et al, 2014, Schraermeyer et al, 2015).…”

Section: Cnv From Human Eyesmentioning

confidence: 99%

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A new rat model of treatment-naive quiescent choroidal neovascularization induced by human VEGF165 overexpression

et al. 2020

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Statement: We developed a new treatment-naive quiescent rat choroidal neovascularization model by VEGF overexpression, allowing the long-term investigation of new drugs. Abstract VEGF is a crucial stimulator for choroidal neovascularization (CNV). Our aim was to develop a reproducible and valid treatment-naive quiescent CNV (i.e. without signs of exudation and with normal visual acuity) rat model by subretinal injection of an adeno-associated virus (AAV)-VEGFA165 vector. The CNV development was longitudinally followed up in vivo by scanning laser ophthalmoscopy/optical coherence tomography, fluorescein and indocyanine green angiographies and ex vivo by electron microscopy (EM) and immunohistochemistry. In total, 57 eyes were analysed. In vivo, a quiescent CNV was observed in 93% of the eyes six weeks post-transduction. In EM, CNV vessels with few fenestrations, multi-layered basement membranes, and bifurcation of endothelial cells were observed sharing the human CNV features.Human VEGF overexpression, multi-layered RPE (RPE65) and macrophages/activated microglia (Iba1) were also detected. In addition, 19 CNV eyes were treated up to three weeks with bevacizumab. The retinal and the CNV lesion thickness decreased significantly in bevacizumab-treated CNV eyes compared to untreated CNV eyes one week after the treatment.In conclusion, our experimental CNV resembles those seen in patients suffering from treatment-naive quiescent CNV in wet-age related macular degeneration, and responses to short-term treatment with bevacizumab. Our new model can, therefore, be used to test the long-term effect of new drugs targeting CNV under precisely defined conditions.

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Section: Overexpression Of Vegf Leads To the Hyperpermeability Of Thesupporting

confidence: 52%

“…Multi-layered basement membranes were often observed around the CNV vessels ( Fig. 4D), which is also a feature of human CNV (Schraermeyer et al, 2015).…”

Section: As Shown In Figs 3 4 the Cnv Induced By Vegf Overexpressiomentioning

confidence: 74%

“…4B). The endothelium of the CNV vessels (Schraermeyer et al, 2015). Multi-layered basement membranes were often observed around the CNV vessels ( Fig.…”

Section: As Shown In Figs 3 4 the Cnv Induced By Vegf Overexpressiomentioning

confidence: 98%

“…Five human CNV samples removed during sub-macular surgery were analyzed by LM/EM and IHC (the same samples used in (Biesemeier et al, 2014, Schraermeyer et al, 2015).…”

Section: Cnv From Human Eyesmentioning

confidence: 99%

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A new rat model of treatment-naive quiescent choroidal neovascularization induced by human VEGF165 overexpression

et al. 2020

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“…TEM analysis of these pillars and the surrounding vasculature suggests loose tight-junctions and loose connections of the smooth muscle cells to the endothelial cells. As previously described endothelial luminal processes (ELPs) which may take the form of "labyrinth-like" vessels in patients of CNV related wet AMD 188 , are also present in the zebrafish. This suggests that intussuception is likely the process in the human patients for the early expansion of CCs.…”

Section: Discussionmentioning

confidence: 82%

Investigating mechanisms of angiogenesis in health and disease using zebrafish models

Ali

2018

Linköping University Medical Dissertations

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Angiogenesis, the growth of blood vessels from an existing vasculature, can occur by sprouting from preexisting vessels or by vessel splitting (intussusception). Pathological angiogenesis drives choroidal neovascularization (CNV) in age related macular degeneration (AMD) which is commonly restricted under the retinal pigment epithelium (RPE), called occult CNV, but may also involve vessels penetrating through the RPE into the sub-retinal space. Pathological vessels are poorly developed, insufficiently perfused and highly leaky, phenotypes that are considered to drive disease progression and lead to poor prognosis. Currently, a number of anti-angiogenic drugs exists, the majority of which target vascular endothelial factor (VEGF), but although they often are highly beneficial for treating eye diseases in the short-term, they are generally of limited efficacy in other diseases such as cancer, and also have poorer efficacy when used for treatment of eye diseases in the long-term. A better understanding of the mechanisms underlying pathological angiogenesis can generate new targets for treatment leading to development of better drugs for cancer and retinopathies, but perhaps also other angiogenesis-dependent diseases, in the future. In this thesis mechanisms involved in developmental angiogenesis or pathological angiogenesis in the choroid, cornea or melanoma was identified. These findings highlight the need to further elaborate our knowledge related to angiogenesis in different tissues/conditions for a more targeted, and potentially effective treatment of diseases in the future.

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Effects of intravitreally injected Fc fragment on rat eyes

Taubitz

Steinbrenner

Tschulakow

et al. 2016

Graefes Arch Clin Exp Ophthalmol

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Biotin labeling is ideal for investigating the distribution of intravitreally injected proteins in ocular tissue. Fc fragments at a dose corresponding to their concentration in standard AMD treatments induced inflammation, and particularly the attraction of immune-competent cells. This may be associated with the risk of inflammation or endophthalmitis after anti-VEGF treatment, and needs further investigation.

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A new kind of labyrinth-like capillary is responsible for leakage from human choroidal neovascular endothelium, as investigated by high-resolution electron microscopy

Cited by 5 publications

References 32 publications

A new rat model of treatment-naive quiescent choroidal neovascularization induced by human VEGF165 overexpression

A new rat model of treatment-naive quiescent choroidal neovascularization induced by human VEGF165 overexpression

Investigating mechanisms of angiogenesis in health and disease using zebrafish models

Effects of intravitreally injected Fc fragment on rat eyes

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