Morphometry of retinal vasculature in Antarctic fishes is dependent upon the level of hemoglobin in circulation

Wujcik, Jody M.; Wang, George; Eastman, Joseph T.; Sidell, Bruce D.

doi:10.1242/jeb.001867

Cited by 31 publications

(24 citation statements)

References 37 publications

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“…Sholl analysis 35 is a morphometric analysis used to quantify dendritic arborization of neurons, and it has also been adapted to measure vascular density. 36,37 A series of concentric circles spaced 50 m apart and centered about the optic nerve head was overlaid onto an image of the vasculature. The number of intersections of the vasculature with circles 100, 150, 200, and 250 m from the distal vascular front (supplemental Figure 2) was quantified.…”

Section: Inhibition Of Cxcr4 In Vivo Alters Tip Cell Morphologymentioning

confidence: 99%

Microarray analysis of retinal endothelial tip cells identifies CXCR4 as a mediator of tip cell morphology and branching

Strasser¹,

Kaminker²,

Tessier‐Lavigne³

2010

Blood

248

226

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The development of the vertebrate vascular system is mediated by both genetic patterning of vessels and by angiogenic sprouting in response to hypoxia. Both of these processes depend on the detection of environmental guidance cues by endothelial cells. A specialized subtype of endothelial cell known as the tip cell is thought to be involved in the detection and response to these cues, but the molecular signaling pathways used by tip cells to mediate tissue vascularization remain largely uncharacterized. To identify genes critical to tip cell function, we have developed a method to isolate them using laser capture microdissection, permitting comparison of RNA extracted from endothelial tip cells with that of endothelial stalk cells using microarray analysis. Genes enriched in tip cells include ESM-1, angiopoietin-2, and SLP-76. CXCR4, a receptor for the chemokine stromal-cell derived factor-1, was also identified as a tip cell-enriched gene, and we provide evidence for a novel role for this receptor in mediating tip cell morphology and vascular patterning in the neonatal retina. IntroductionDuring embryogenesis, the vertebrate circulatory system develops through the overlapping processes of vasculogenesis and angiogenesis. Vasculogenesis is the migration and differentiation of endothelial cells from hematopoietic precursors. Angiogenesis involves the sprouting of blood vessel networks and their maturation into an organized, functional circulatory system. 1,2 Many aspects of angiogenesis are also recapitulated in the adult during normal conditions, such as pregnancy, and pathologic situations, such as inflammation and cancer. 3 An understanding of the molecular mechanisms that govern this process is critical for the development of novel proangiogenic and antiangiogenic therapeutics.A specialized subset of endothelial cells known as tip cells is thought to mediate vessel growth and patterning. Tip cells are found at the growing end of a nascent vascular sprout and are characterized by abundant and dynamic filopodia. These filopodia are thought to detect cues in the local environment and translate them into directed motility. 4,5 Tip cells are responsive to angiogenic factors, such as vascular endothelial growth factor-A (VEGF-A), 6 as well as classic axon guidance factors, such as netrin-1. 7 The generation of new tip cells is limited by the activity of Delta-like 4 (Dll4), [8][9][10][11] which is specifically up-regulated in tip cells. 12 Signaling of Dll4 through Notch receptors on adjacent cells has been proposed to inhibit their development into tip cells. 13 Despite these advances, the mechanisms that may promote or mediate the generation of new tip cells remain incompletely understood.Recently, endothelial tip cells have become a topic of intense scrutiny, 3 but many critical questions remain about their function and how they may differ from neighboring stalk cells. Expression of several genes, including VEGF receptor 2 (VEGFR2), 6 Dll4, PDGF-B, 6 and VEGFR3, 14 has been shown to be higher in retinal tip cel...

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Section: Inhibition Of Cxcr4 In Vivo Alters Tip Cell Morphologymentioning

confidence: 99%

Microarray analysis of retinal endothelial tip cells identifies CXCR4 as a mediator of tip cell morphology and branching

Strasser¹,

Kaminker²,

Tessier‐Lavigne³

2010

Blood

248

226

View full text Add to dashboard Cite

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“…Owing to the complex nature of retinal tissue and differences in tissue composition, as demonstrated by the increased vascular endothelial tissue in icefish compared with that of red-blooded species (Wujcik et al, 2007), samples were normalized to total RNA. This was completed by several rounds of careful quantification and dilution until all samples had the same RNA concentration.…”

Section: Measurement Of Vegf Hif-1a and Phd2 Mrna Expression In The mentioning

confidence: 99%

“…During the course of evolution, icefishes developed a unique cardiovascular system that appears to compensate for the loss of Hb. Channichthyids are characterized by increased blood volume, larger bore blood vessels, greater ventricular mass, higher cardiac output, denser vascularization and increased ventricular mitochondrial densities compared with red-blooded Antarctic notothenioids (Eastman, 1993;O'Brien and Sidell, 2000;Wujcik et al, 2007). Together, these cardiovascular characteristics facilitate delivery of oxygen throughout the body.…”

Section: Introductionmentioning

confidence: 99%

Phenylhydrazine-induced anemia causes nitric-oxide-mediated upregulation of the angiogenic pathway in Notothenia coriiceps

Borley

Beers

Sidell

2010

Journal of Experimental Biology

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SUMMARYAntarctic icefishes possess several cardiovascular characteristics that enable them to deliver oxygen adequately in the absence of hemoglobin (Hb). To gain insight into mechanisms driving development of these cardiovascular characteristics of icefish, we chemically induced severe anemia in a red-blooded notothenioid, Notothenia coriiceps. After 10 days of treatment with phenylhydrazine HCl, the hematocrit and Hb concentration of N. coriiceps decreased by >90% and >70%, respectively. Anemic fish exhibited a significantly higher concentration of nitric oxide (NO) metabolites in their plasma compared with that of control animals, indicating that corporeal levels of NO are higher in anemic animals than in control fish. The activity of nitric oxide synthase (NOS) was measured in brain, retina, pectoral muscle and ventricle of control and anemic animals. With the exception of retina, no significant differences in NOS activities were observed, indicating that the increase in plasma NO metabolites is due to loss of Hb, which normally plays a major role in the degradation of NO, and not due to an overall increase in the capacity for NO production. To determine whether loss of Hb can stimulate remodeling of the cardiovascular system, we measured expression of HIF-1a, PHD2 and VEGF mRNA in retinae of control and anemic fish. Expression of all three genes was higher in anemic animals compared with control N. coriiceps, suggesting a causative relationship between loss of Hb and induction of angiogenesis that probably is mediated through nitric oxide signaling.

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“…Icefishes largely compensate for the lack of Hb by utilizing a suite of cardiovascular system modifications: large-bore blood vessels, which are present in high density in some tissues; large blood volumes; and large hearts containing more mitochondria than hearts of similar-sized Hbexpressing fishes (Hemmingsen and Douglas, 1970;Holeton, 1970;Hemmingsen et al, 1972;Fitch et al, 1984;O'Brien and Sidell, 2000;Wujcik, et al, 2007). There is some evidence to support the hypothesis that some of these characteristics or 'hallmark traits' of icefishes, such as enhanced vascular densities (Wujcik et al, 2007), may have originated via pathways mediated by nitric oxide (Sidell and O'Brien, 2006;Beers et al, 2010;Borley et al, 2010). Whatever their mechanism of origin, integration of all of these features allows channichthyids to circulate large blood volumes at relatively high flow rates and, importantly, without excessive pressure development.…”

Section: Loss Of Major Hemoproteinsmentioning

confidence: 99%

Antarctic notothenioid fish: what are the future consequences of ‘losses’ and ‘gains’ acquired during long-term evolution at cold and stable temperatures?

Beers

Jayasundara

2015

Journal of Experimental Biology

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Antarctic notothenioids dominate the fish fauna of the Southern Ocean. Evolution for millions of years at cold and stable temperatures has led to the acquisition of numerous biochemical traits that allow these fishes to thrive in sub-zero waters. The gain of antifreeze glycoproteins has afforded notothenioids the ability to avert freezing and survive at temperatures often hovering near the freezing point of seawater. Additionally, possession of cold-adapted proteins and membranes permits them to sustain appropriate metabolic rates at exceptionally low body temperatures. The notothenioid genome is also distinguished by the disappearance of traits in some species, losses that might prove costly in a warmer environment. Perhaps the best-illustrated example is the lack of expression of hemoglobin in white-blooded icefishes from the family Channichthyidae. Loss of key elements of the cellular stress response, notably the heat shock response, has also been observed. Along with their attainment of cold tolerance, notothenioids have developed an extreme stenothermy and many species perish at temperatures only a few degrees above their habitat temperatures. Thus, in light of today's rapidly changing climate, it is critical to evaluate how these extreme stenotherms will respond to rising ocean temperatures. It is conceivable that the remarkable cold specialization of notothenioids may ultimately leave them vulnerable to future thermal increases and threaten their fitness and survival. Within this context, our review provides a current summary of the biochemical losses and gains that are known for notothenioids and examines these cold-adapted traits with a focus on processes underlying thermal tolerance and acclimation capacity.

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Morphometry of retinal vasculature in Antarctic fishes is dependent upon the level of hemoglobin in circulation

Cited by 31 publications

References 37 publications

Microarray analysis of retinal endothelial tip cells identifies CXCR4 as a mediator of tip cell morphology and branching

Microarray analysis of retinal endothelial tip cells identifies CXCR4 as a mediator of tip cell morphology and branching

Phenylhydrazine-induced anemia causes nitric-oxide-mediated upregulation of the angiogenic pathway in Notothenia coriiceps

Antarctic notothenioid fish: what are the future consequences of ‘losses’ and ‘gains’ acquired during long-term evolution at cold and stable temperatures?

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