Vascular Endothelial Cell Growth Factors Promote the <i>In Vitro</i> Development of Rat Photoreceptor Cells

Yourey, P. A.; Gohari, Shiva; Su, Jeffery; Alderson, Ralph

doi:10.1523/jneurosci.20-18-06781.2000

Cited by 94 publications

(56 citation statements)

References 38 publications

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“…It has been reported that VEGF promotes rhodopsin expression in neonatal rat retinal monolayer cultures (Yourey et al, 2000). Here, we reveal a novel function of VEGF in modulating production of the first-born retinal neurons.…”

Section: Discussionmentioning

confidence: 61%

VEGF activates divergent intracellular signaling components to regulate retinal progenitor cell proliferation and neuronal differentiation

Hashimoto¹,

Zhang²,

Chen³

et al. 2006

Development

116

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During vertebrate neurogenesis, multiple extracellular signals influence progenitor cell fate choices. The process by which uncommitted progenitor cells interpret and integrate signals is not well understood. We demonstrate here that in the avascular chicken retina, vascular endothelial growth factor (VEGF) secreted by postmitotic neurons acts through the FLK1 receptor present on progenitor cells to influence cell proliferation and commitment. Augmenting VEGF signals increases progenitor cell proliferation and decreases retinal ganglion cell genesis. Conversely, absorbing endogenous VEGF ligand or disrupting FLK1 activity attenuates cell proliferation and enhances retinal ganglion cell production. In addition, we provide evidence that VEGF signals transmitted by the FLK1 receptor activate divergent intracellular signaling components, which regulate different responses of progenitor cells. VEGF-induced proliferation is influenced by the MEK-ERK pathway, as well as by the basic helix-loop-helix factor HES1. By contrast, VEGF-dependent ganglion cell suppression does not require MEK-ERK activation, but instead relies on VEGF-stimulated HES1 activity, which is independent of NOTCH signaling. Moreover, elevated HES1 expression promotes progenitor cell proliferation and prevents overproduction of retinal ganglion cells owing to the loss of VEGF or sonic hedgehog (SHH), another signal that suppresses ganglion cell development. Based on previous and current findings, we propose that HES1 serves as a convergent signaling node within early retinal progenitor cells to integrate various cell-extrinsic cues, including VEGF and SHH, in order to control cell proliferation and neuronal specification.

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Section: Discussionmentioning

confidence: 61%

VEGF activates divergent intracellular signaling components to regulate retinal progenitor cell proliferation and neuronal differentiation

Hashimoto¹,

Zhang²,

Chen³

et al. 2006

Development

116

View full text Add to dashboard Cite

show abstract

“…Comparatively little is known regarding the possible role of VEGF in adult neurogenesis, although other growth factors, including epidermal growth factor (EGF) (12), fibroblast growth factor-2 (FGF-2) (13), brain-derived neurotrophic factor (BDNF) (14), and erythropoietin (15), have been implicated. In addition, the VEGF receptor Flk-1 is expressed in neural progenitor cells of the mouse retina (16), and its activation stimulates their differentiation into amacrine neurons and photoreceptor cells (17). Finally, neurogenesis in the adult SGZ appears to occur in intimate association with angiogenesis, suggesting that common factors, such as VEGF, might be involved in both processes (18).…”

mentioning

confidence: 99%

Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo

Jin

Zhu

Sun

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

1,383

989

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“…Conceivably, treatment of the retinal vasculature could result in improved visual function (e.g., contrast sensitivity) by an associated beneficial effect on the postreceptor neurons. However, treatment of ROP by manipulating growth factors must be approached with considerable caution because the same growth factors regulate the developing photorececeptors and postreceptor retinal neurons [35,36]. Indeed, particular caution in use of anti-VEGF treatment in immature retina has been advised specifically because of the potential for adverse effects on the developing neurons [37].…”

mentioning

confidence: 99%

Retinal degenerative and hypoxic ischemic disease

et al. 2008

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A broad spectrum of retinal diseases affects both the retinal vasculature and the neural retina, including photoreceptor and postreceptor layers. The accepted clinical hallmarks of acute retinopathy of prematurity (ROP) are dilation and tortuosity of the retinal vasculature. Additionally, significant early and persistent effects on photoreceptor and postreceptor neural structures and function are demonstrated in ROP. In this paper, we focus on the results of longitudinal studies of electroretinographic (ERG) and vascular features in rats with induced retinopathies that model the gamut of human ROP, mild to severe. Two potential targets for pharmaceutical interventions emerge from the observations. The first target is immature photoreceptors because the status of the photoreceptors at an early age predicts later vascular outcome; this approach is appealing as it holds promise to prevent ROP. The second target is the interplay of the neural and vascular retinal networks, which develop cooperatively. Beneficial pharmaceutical interventions may be measured in improved visual outcome as well as lessening of the vascular abnormalities.As a system, the mammalian retina is vulnerable to diseases that affect the exquisitely balanced interplay of the neural retina and the vasculature that nourishes it. Visual loss occurs when this balance is disturbed. On the one hand, diseases such as photoreceptor degenerations that primarily affect the neural retina also affect the retinal vasculature. On the other hand, diseases that are clinically characterized by abnormality in the choroidal or retinal vasculature, such as age related macular degeneration, diabetic retinopathy, and retinopathy of prematurity (ROP), also affect the retinal neurons. Thus, all such diseases fall within the broad group of hypoxic ischemic disorders of neural tissue. Photoreceptors, specialized cells that have the highest oxygen requirements of any cell in the body [1], are likely important in all hypoxic ischemic diseases of the retina. Translation from animal models to patientsThe photoreceptors are nestled closely to the choroidal vasculature (figure 1). Highly organized postreceptor retinal neurons form layers that are supplied by the retinal vessels. Although the choroid is the principal supply to the photoreceptors, degeneration of the photoreceptors is, nonetheless, associated with attenuation of the retinal arterioles [2]. Because the photoreceptor layer is such an extraordinary oxygen sink, it is presumed that, as photoreceptors degenerate, their metabolic demands wane and the retinal vasculature becomes attenuated consequent to the neural retina's chronic lower requirement for oxygen [2]. NIH-PA Author ManuscriptA tight link between the photoreceptors and the retinal vascular network is evident in the developing retina. Postreceptor cells differentiate before the photoreceptors, which are the last retinal cells to mature. As the formation of rod outer segments advances in a posterior to peripheral gradient, so too does vascular coverag...

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Vascular Endothelial Cell Growth Factors Promote the In Vitro Development of Rat Photoreceptor Cells

Cited by 94 publications

References 38 publications

VEGF activates divergent intracellular signaling components to regulate retinal progenitor cell proliferation and neuronal differentiation

VEGF activates divergent intracellular signaling components to regulate retinal progenitor cell proliferation and neuronal differentiation

Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo

Retinal degenerative and hypoxic ischemic disease

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