Time-Lapse Imaging of Vitreoretinal Angiogenesis Originating from Both Quiescent and Mature Vessels in a Novel Ex Vivo System

Murakami, Tomoaki; Suzuma, Kiyoshi; Takagi, Hitoshi; Kita, Mihori; Ohashi, Hirokazu; Watanabe, Dai; Ojima, T.; Kurimoto, Masafumi; Kimura, Tomio; Sakamoto, Atsushi; Unoki, Noriharu; Yoshimura, Nagahisa

doi:10.1167/iovs.06-0373

Cited by 22 publications

(28 citation statements)

References 40 publications

(38 reference statements)

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“…6A, yellow arrows indicate direction of sprout movement), as has been observed in other model systems (Murakami et al, 2006). We plotted the elongation rate of the sprouts (Fig.…”

Section: Sprout Location Can Be Predicted Based On Flow Dynamicsmentioning

confidence: 76%

Flow dynamics control the location of sprouting and direct elongation during developmental angiogenesis

2015

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Angiogenesis is tightly controlled by a number of signalling pathways. Although our understanding of the molecular mechanisms involved in angiogenesis has rapidly increased, the role that biomechanical signals play in this process is understudied. We recently developed a technique to simultaneously analyse flow dynamics and vascular remodelling by time-lapse microscopy in the capillary plexus of avian embryos and used this to study the hemodynamic environment present during angiogenic sprouting. We found that sprouts always form from a vessel at lower pressure towards a vessel at higher pressure, and that sprouts form at the location of a shear stress minimum, but avoid locations where two blood streams merge even if this point is at a lower level of shear stress than the sprouting location. Using these parameters, we were able to successfully predict sprout location in quail embryos. We also found that the pressure difference between two vessels is permissive to elongation, and that sprouts will either change direction or regress if the pressure difference becomes negative. Furthermore, the sprout elongation rate is proportional to the pressure difference between the two vessels. Our results show that flow dynamics are predictive of the location of sprout formation in perfused vascular networks and that pressure differences across the interstitium can guide sprout elongation.

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“…6A, yellow arrows indicate direction of sprout movement), as has been observed in other model systems (Murakami et al, 2006). We plotted the elongation rate of the sprouts (Fig.…”

Section: Sprout Location Can Be Predicted Based On Flow Dynamicsmentioning

confidence: 76%

Flow dynamics control the location of sprouting and direct elongation during developmental angiogenesis

2015

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“…Recent ex vivo studies of retinal explants in short-term culture suggest that the dynamic analysis of ongoing retinal vascular sprouting might be feasible (Murakami et al, 2006;Sawamiphak et al, 2010;Unoki et al, 2010b). In this approach, retinas are dissected, placed on a filter and covered with a collagen matrix.…”

Section: Retinal Explant Culturesmentioning

confidence: 99%

“…In this approach, retinas are dissected, placed on a filter and covered with a collagen matrix. VEGF is then used to induce sprouting of the retinal vessels (Murakami et al, 2006). In this model, the normal endogenous tissue gradient of VEGF is likely to be disrupted, and directional guidance and balanced EC proliferation might not be comparable with the in vivo situation.…”

Section: Retinal Explant Culturesmentioning

confidence: 99%

Coordinating cell behaviour during blood vessel formation

2011

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SummaryThe correct development of blood vessels is crucial for all aspects of tissue growth and physiology in vertebrates. The formation of an elaborate hierarchically branched network of endothelial tubes, through either angiogenesis or vasculogenesis, relies on a series of coordinated morphogenic events, but how individual endothelial cells adopt specific phenotypes and how they coordinate their behaviour during vascular patterning is unclear. Recent progress in our understanding of blood vessel formation has been driven by advanced imaging techniques and detailed analyses that have used a combination of powerful in vitro, in vivo and in silico model systems. Here, we summarise these models and discuss their advantages and disadvantages. We then review the different stages of blood vessel development, highlighting the cellular mechanisms and molecular players involved at each step and focusing on cell specification and coordination within the network.

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“…Furthermore, pericytes provide microvascular stability as vascular remodeling ceases upon pericyte investment [17], and are implicated in endothelial growth arrest as impaired pericyte recruitment leads to endothelial hyperplasia in vivo [26]. Angiogenic sprouts emanate from pericyte-deficient microvascular domains as novel imaging techniques demonstrate [27]. Together, loss or decrease of pericyte abundance may lead to end-stage microvascular damage preceding the proliferative angiogenic response.…”

Section: Pericytesmentioning

confidence: 99%

Microvascular Modifications in Diabetic Retinopathy

2011

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Patients struggling with diabetes are at elevated risks for several sight-threatening diseases, including proliferative diabetic retinopathy (DR). DR manifests in two stages: first, the retinal microvasculature is compromised and capillary degeneration occurs; subsequently, an over-compensatory angiogenic response is initiated. Early changes in the retinal microcirculation include disruptions in blood flow, thickening of basement membrane, eventual loss of mural cells, and the genesis of acellular capillaries. Endothelial apoptosis and capillary dropout lead to a hypoxic inner retina, alterations in growth factors, and upregulation of inflammatory mediators. With disease progression, pathologic angiogenesis generates abnormal preretinal microvessels. Current therapies, which include panretinal photocoagulation and vitrectomy, have remained unaltered for several decades. With several exciting preclinical advances, emergent technologies and innovative cellular targets may offer newfound hope for developing "next-generation" interventional or preventive clinical approaches that will significantly advance current standards of care and clinical outcomes.

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Time-Lapse Imaging of Vitreoretinal Angiogenesis Originating from Both Quiescent and Mature Vessels in a Novel Ex Vivo System

Abstract: Time-lapse imaging of this system visualized the dynamic process in vitreoretinal neovascularization from quiescent and mature vessels.

Cited by 22 publications

References 40 publications

Flow dynamics control the location of sprouting and direct elongation during developmental angiogenesis

Flow dynamics control the location of sprouting and direct elongation during developmental angiogenesis

Coordinating cell behaviour during blood vessel formation

Microvascular Modifications in Diabetic Retinopathy

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