Astrocyte Proliferation During Development of the Human Retinal Vasculature

Sandercoe, Trent M; Madigan, Michele C.; Billson, Francis A.; Penfold, Philip L.; Provis, Jan

doi:10.1006/exer.1999.0730

Cited by 43 publications

(27 citation statements)

References 32 publications

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“…There is a close correlation between migration of retinal astrocytes, expression of VEGF and development of the superficial vascular plexus; the avascular fovea in humans does not contain astrocytes (Chan-Ling et al, 1992;Holash and Stewart, 1993;Gariano et al, 1994;Jiang et al, 1994;Sandercoe et al, 1999;Dorrell et al, 2002;Fruttiger, 2007). Initially, superficial blood vessels follow the central to peripheral gradient of retinal astrocyte maturation towards the periphery of the retina, which is reached by P8 in mice, P12 in rats and 32 weeks gestation in the human.…”

Section: 21mentioning

confidence: 99%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

636

527

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Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the U.S., for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40 kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis.

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Section: 21mentioning

confidence: 99%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

636

527

View full text Add to dashboard Cite

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“…Astrocytes emerge from the optic nerve head around birth and spread as a proliferating cell population across the inner surface of the retina (Stone and Dreher, 1987;Watanabe and Raff, 1988;Ling et al, 1989;Sandercoe et al, 1999). The resulting network of astrocytes acts as a template for the developing retinal vasculature, which also spreads out from the optic nerve head (Jiang et al, 1995;Zhang and Stone, 1997;Fruttiger, 2002).…”

Section: Introductionmentioning

confidence: 99%

Stabilization of the retinal vascular network by reciprocal feedback between blood vessels and astrocytes

2005

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Development of the retinal vasculature is controlled by a hierarchy of interactions among retinal neurons, astrocytes and blood vessels. Retinal neurons release platelet-derived growth factor (PDGFA) to stimulate proliferation of astrocytes, which in turn stimulate blood vessel growth by secreting vascular endothelial cell growth factor (VEGF). Presumably, there must be counteractive mechanisms for limiting astrocyte proliferation and VEGF production to prevent runaway angiogenesis. Here, we present evidence that the developing vessels provide feedback signals that trigger astrocyte differentiation – marked by cessation of cell division, upregulation of glial fibrillary acidic protein (GFAP) and downregulation of VEGF. We prevented retinal vessel development by raising newborn mice in a high-oxygen atmosphere, which leads, paradoxically, to retinal hypoxia (confirmed by using the oxygen-sensing reagent EF5). The forced absence of vessels caused prolonged astrocyte proliferation and inhibited astrocyte differentiation in vivo. We could reproduce these effects by culturing retinal astrocytes in a low oxygen atmosphere, raising the possibility that blood-borne oxygen itself might induce astrocyte differentiation and indirectly prevent further elaboration of the vascular network.

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“…A number of elegant immunohistochemical wholemount studies have examined different cell types in relationship to blood vessel development and suggested that there is an intimate concomitant relationship between the astrocytes and forming blood vessels (Chan-Ling et al, 2004). Sandercoe et al used double labeling with CD34/Ki67 and GFAP/Ki67 in whole-mounts and found that, at 18 weeks gestation, the majority of proliferating cells associ-ated with developing vessels were astrocytes (Sandercoe et al, 1999). More recently, astrocyte precursor cells (APCs) have been described in developing fetal human retina as well as a population of angioblasts (Chu et al, 2001;Chan-Ling et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

The initial fetal human retinal vasculature develops by vasculogenesis

McLeod

Hasegawa

Prow

et al. 2006

Developmental Dynamics

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There is increasing evidence that the hemangioblast, a common progenitor for hematopoietic cells and endothelial cells, participates in embryonic and extra-embryonic vasculogenesis in some organs. Whether resident angioblasts or endothelial progenitor cells (EPCs) contribute to human retinal vasculogenesis is still a matter of controversy. To address this controversy, fetal human retinas of 6 -23 weeks gestation (WG) were examined using immunohistochemistry and a panel of antibodies against endothelial cell markers (CD34, CD31), a marker for retinal angioblasts and endothelium (CD39/ecto-ADPase), and a marker for precursors and hemangioblasts (CXCR4). Confocal microscopic spectral analysis and double labeling with Ki67 was used to identify the proliferating cell types. In the inner neuroblastic layer of the 6 -8 WG retina and in the putative ganglion cell layer in avascular regions of older eyes (14 WG-20 WG), scattered CD39 ؉ angioblasts were well in advance of forming vasculature. There was a layer of CXCR4 ؉ cells in the inner retina that was reduced in size with development. As blood vessels formed, CD39؉ cells were always well in advance of the vascular front and they expressed CXCR4. This demonstrates that a pool of resident angioblasts express CD39 and CXCR4 as they differentiate and participate in vasculogenesis in the fetal human. They retain expression of CD39 as endothelial cells in the newly formed retinal vasculature but they down-regulate CXCR4 expression. Developmental Dynamics 235:3336 -3347, 2006.

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Astrocyte Proliferation During Development of the Human Retinal Vasculature

Cited by 43 publications

References 32 publications

Vascular endothelial growth factor in eye disease

Vascular endothelial growth factor in eye disease

Stabilization of the retinal vascular network by reciprocal feedback between blood vessels and astrocytes

The initial fetal human retinal vasculature develops by vasculogenesis

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