Expression of hypoxia-inducible factor−1α and −2α in human choroidal neovascular membranes

Sheridan, Carl; Pate, S.; Hiscott, Paul; Wong, David; Pattwell, David M.; Kent, David

doi:10.1007/s00417-009-1133-3

Cited by 78 publications

(60 citation statements)

References 27 publications

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“…This may lead to reduced oxygen tension causing the activation of a hypoxic response, which may lead to the development of neovascular complications. In this response, HIF factors may again be the driving force controlling initiation and progression of the devastating vessel growth (Inoue et al, 2007;Sheridan et al, 2009). The main pro-angiogenic factor in wet AMD seems to be VEGF.…”

Section: Age-related Macular Degenerationmentioning

confidence: 99%

Hypoxia in the Eye: A Two-Sided Coin

Grimm

Willmann

2012

High Altitude Medicine & Biology

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Grimm, Christian, Gabriel Willman. Hypoxia in the eye: A two-sided coin. High Alt Med Biol. 13:169-175, 2012.-Tissue oxygenation in general and hypoxia in particular are important regulators of retinal physiology and pathophysiology. Reduced oxygen tension and hypoxia-inducible transcription factors along with some of their target genes are critically involved in retinal development, and especially in the generation of a normal retinal vasculature. Well-timed hypoxia is thus vital for the young eye to establish proper retinal function and vision. However, when hypoxia is ill-timed, reduced oxygen tension may be associated with the development of retinal pathologies, including retinopathy of prematurity, diabetic retinopathy, glaucoma, age-related macular degeneration, or high altitude retinopathy. Here, reduced oxygen tension activates a hypoxic response that culminates in an increased expression of vascular endothelial growth factor. This causes pathological neovascularization of the delicate neuronal retina, a process that may ultimately lead to loss of vision. In contrast, preconditioning by welldefined and controlled short-term hypoxia is not devastating for the retina but instead induces a molecular response that provides protection to neuronal cells. Detailed investigation of hypoxic mechanisms during development and adulthood may thus reveal factors, which may be targeted by therapeutic approaches to save and preserve vision in patients.

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Section: Age-related Macular Degenerationmentioning

confidence: 99%

Hypoxia in the Eye: A Two-Sided Coin

Grimm

Willmann

2012

High Altitude Medicine & Biology

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“…Retinal pigment epithelial (RPE) cells, located between the neurosensory retina and the vascular choroids, form the outer blood retinal barrier and have an important role in the pathogenesis of CNV (2). Hypoxia is also essential for the pathogenesis of CNV (3). Increasing research suggests that vascular endothelial growth factor (VEGF) upregulation produced by RPE cells under hypoxic conditions is a major angiogenic factor for CNV (4,5).…”

Section: Introductionmentioning

confidence: 99%

Knockdown of dickkopf2 inhibits vascular endothelia growth factor expression through the Wnt/β-catenin signaling pathway in human retinal pigment epithelial cells under hypoxic conditions

Zhao

Liu

et al. 2018

Exp Ther Med

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Abstract. Hypoxia has been demonstrated to be a proangiogenic factor that induces vascular endothelial growth factor (VEGF) in retinal pigment epithelial (RPE) cells. Dickkopf2 (DKK2), originally known as Wnt antagonist, has recently been demonstrated to have an important regulatory role in angiogenesis; however, the specific role of DKK2 in RPE cells is not known. In the present study, the effects of DKK2 on VEGF expression under hypoxic conditions were investigated, as well as the molecular mechanisms involved. The results demonstrated that the expression of DKK2 was markedly increased under hypoxic conditions compared with normoxic conditions. Knockdown of DKK2 markedly attenuated the CoCl 2 -induced expression of hypoxia-inducible factor (HIF)-1α and VEGF in RPE cells. Furthermore, knockdown of DKK2 markedly inhibited the expression of β-catenin induced by hypoxia. In conclusion, the findings of the present study demonstrate that knockdown of DKK2 inhibits the hypoxia-induced production of VEGF by suppressing the activation of the Wnt/β-catenin signaling pathway.

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“…Recently, it has also been shown that CNV membranes are positive for HIF-1 expression, and this expression tends to be localized to the retinal pigment epithelium (RPE) cells. 23, 24 As a 'master switch' for mammalian circulation in response to low oxygen tension, HIF-1 regulates the transcription of many proangiogenic growth factors, including VEGF, erythropoietin and platelet-derived growth factor. 25,26 Knocking down of HIF-1a gene results in the down regulation of VEGF.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory efficacy of hypoxia-inducible factor 1α short hairpin RNA plasmid DNA-loaded poly (D, L-lactide-co-glycolide) nanoparticles on choroidal neovascularization in a laser-induced rat model

Zhang

et al. 2009

Gene Ther

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The aim of this study was to evaluate the possibility of poly (D, L-lactide-co-glycolide) nanoparticle (NPs) as a gene vector for functional plasmid DNA (pDNA) and to investigate its inhibitory efficacy on experimental choroidal neovascularization (CNV). We developed intravitreal administered, hypoxia-inducible factor 1a (HIF-1a) short hairpin RNA and green fluorescent protein (GFP) co-expressed pDNA-loaded NPs (pshHIF-1a NPs). CNV was induced by laser photocoagulation in 112 rats. The rats were then randomly assigned to be injected intravitreally with phosphate-buffered saline (PBS), blank NPs, naked pDNA, control pDNA NPs and pshHIF-1a NPs, respectively, and non-injection group was set as the control. Immunofluorescence staining, fluorescein fundus angiography and histologic analysis were performed to evaluate the inhibitory efficacy on CNV. The results showed that the expression of GFP preferentially localized in the retinal pigment epithelium cell layer and lasted for 4 weeks. The fluorescein leakage areas of CNV were significantly larger in the PBS, blank NPs, control pDNA NPs, non-injection group and naked pDNA group than in pshHIF-1a NPs group (Po0.01). The mean thickness of the CNV lesions in the intravitreally pshHIF1a NPs-treated group was significantly smaller than other groups (Po0.01). No signs of functional or ultrastructural destruction in retina were detected. Therefore, pshHIF-1a NPs may act as a novel therapeutic option to transfer specific pDNA and inhibit the formation of experimental CNV.

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Expression of hypoxia-inducible factor−1α and −2α in human choroidal neovascular membranes

Abstract: The localization of HIF expression supports the concept that hypoxia is a major stimulus for the development of submacular wound healing and within this context CNV is but one component of this process.

Cited by 78 publications

References 27 publications

Hypoxia in the Eye: A Two-Sided Coin

Hypoxia in the Eye: A Two-Sided Coin

Knockdown of dickkopf2 inhibits vascular endothelia growth factor expression through the Wnt/β-catenin signaling pathway in human retinal pigment epithelial cells under hypoxic conditions

Inhibitory efficacy of hypoxia-inducible factor 1α short hairpin RNA plasmid DNA-loaded poly (D, L-lactide-co-glycolide) nanoparticles on choroidal neovascularization in a laser-induced rat model

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