Hypoxia in Vascular Networks: A Complex System Approach to Unravel the Diabetic Paradox

Gandica, Yérali; Tobias, Schwarz; Oliveira, Orlando; Travasso, Rui D. M.

doi:10.1371/journal.pone.0113165

Cited by 10 publications

(10 citation statements)

References 54 publications

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“…Proliferation of new capillaries from the existing retinal vessels or remodeling of collateral vessels may occur in severe retinal hypoxia. 25 There might be a mild hypoxia in th-minor which may affect retinal microcirculation. But there was no difference in the ratio of mean arteriolar caliber to mean venular caliber between groups.…”

Section: Discussionmentioning

confidence: 99%

Retinal nerve fiber layer thickness and retinal vessel calibers in children with thalassemia minor

et al. 2016

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Objectives:Evaluation of the peripapillary retinal nerve fiber layer thickness, subfoveal choroidal thickness, and retinal vessel caliber measurements in children with thalassemia minor.Methods:In this cross-sectional and comparative study, 30 thalassemia minor patients and 36 controls were included. Heidelberg spectral domain optical coherence tomography was used for peripapillary retinal nerve fiber layer thickness, subfoveal choroidal thickness, and retinal vessel caliber measurements.Results:There was no statistically significant difference in retinal nerve fiber layer thickness and subfoveal choroidal thickness between the two groups (p > 0.05). There was no correlation between retinal nerve fiber layer thickness and hemoglobin values. Both the arterioral and venular calibers were higher in thalassemia minor group (p < 0.05).Conclusion:There is increased retinal arterioral and venular calibers in children with thalassemia minor compared with controls.

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Section: Discussionmentioning

confidence: 99%

Retinal nerve fiber layer thickness and retinal vessel calibers in children with thalassemia minor

et al. 2016

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“…Unlike this study, Gandica et al . [ 115 ] developed a computational model of retinal ischemia studying the effect of critical sizes and densities of localized blockages of retinal vasculature on the emergence of diabetic retinopathy. In their model, various sizes of local blockages of vessels, assumedly caused by destabilizing proteins such as Angiopoietin-2, were randomly distributed in the region of interest and areas of derived hypoxia were examined regarded as an indicator of potential phenotypes of diabetic retinopathy.…”

Section: Methodsmentioning

confidence: 99%

“…Other boundary nodes with incoming blood flow are assigned with oxygen tensions of smaller values ( S15 Fig ). Hypoxia-induced elevated secretion of VEGF in Mueller cells is known as an occurrence in diabetic retinopathy [ 115 – 117 ]. FAZ region is treated as a sink for VEGF.…”

Section: Methodsmentioning

confidence: 99%

Progression of Diabetic Capillary Occlusion: A Model

Gens

Glazier

et al. 2016

PLoS Comput Biol

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An explanatory computational model is developed of the contiguous areas of retinal capillary loss which play a large role in diabetic maculapathy and diabetic retinal neovascularization. Strictly random leukocyte mediated capillary occlusion cannot explain the occurrence of large contiguous areas of retinal ischemia. Therefore occlusion of an individual capillary must increase the probability of occlusion of surrounding capillaries. A retinal perifoveal vascular sector as well as a peripheral retinal capillary network and a deleted hexagonal capillary network are modelled using Compucell3D. The perifoveal modelling produces a pattern of spreading capillary loss with associated macular edema. In the peripheral network, spreading ischemia results from the progressive loss of the ladder capillaries which connect peripheral arterioles and venules. System blood flow was elevated in the macular model before a later reduction in flow in cases with progression of capillary occlusions. Simulations differing only in initial vascular network structures but with identical dynamics for oxygen, growth factors and vascular occlusions, replicate key clinical observations of ischemia and macular edema in the posterior pole and ischemia in the retinal periphery. The simulation results also seem consistent with quantitative data on macular blood flow and qualitative data on venous oxygenation. One computational model applied to distinct capillary networks in different retinal regions yielded results comparable to clinical observations in those regions.

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“…This process leads to the formation of neo-vessel networks that irrigate tumors and other hypoxic tissues. In the circumstances in which these neo-vessel networks are functional, they present a ramified hierarchical tree-like structure at large scale, as observed in various tissues (from the mesenteric arteries, to the retina) 10 – 14 , while at microvascular scale the capillaries form a lattice-like network connecting the arterial and venous vascular trees 10 , 14 , as seen in reconstructed mouse vascular networks in ref. 15 and used in a tumor model in ref.…”

Section: Introductionmentioning

confidence: 86%

Angiogenic Factors produced by Hypoxic Cells are a leading driver of Anastomoses in Sprouting Angiogenesis–a computational study

Moreira-Soares

Coimbra

Rebelo

et al. 2018

Sci Rep

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Angiogenesis - the growth of new blood vessels from a pre-existing vasculature - is key in both physiological processes and on several pathological scenarios such as cancer progression or diabetic retinopathy. For the new vascular networks to be functional, it is required that the growing sprouts merge either with an existing functional mature vessel or with another growing sprout. This process is called anastomosis. We present a systematic 2D and 3D computational study of vessel growth in a tissue to address the capability of angiogenic factor gradients to drive anastomosis formation. We consider that these growth factors are produced only by tissue cells in hypoxia, i.e. until nearby vessels merge and become capable of carrying blood and irrigating their vicinity. We demonstrate that this increased production of angiogenic factors by hypoxic cells is able to promote vessel anastomoses events in both 2D and 3D. The simulations also verify that the morphology of these networks has an increased resilience toward variations in the endothelial cell’s proliferation and chemotactic response. The distribution of tissue cells and the concentration of the growth factors they produce are the major factors in determining the final morphology of the network.

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Hypoxia in Vascular Networks: A Complex System Approach to Unravel the Diabetic Paradox

Cited by 10 publications

References 54 publications

Retinal nerve fiber layer thickness and retinal vessel calibers in children with thalassemia minor

Retinal nerve fiber layer thickness and retinal vessel calibers in children with thalassemia minor

Progression of Diabetic Capillary Occlusion: A Model

Angiogenic Factors produced by Hypoxic Cells are a leading driver of Anastomoses in Sprouting Angiogenesis–a computational study

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