Vascular endothelial growth factors and placenta growth factor in retinal vasculopathies: Current research and future perspectives

Mesquita, Joana; Castro-de-Sousa, João Paulo; Vaz-Pereira, Sara; Neves, A.; Passarinha, Luís A.; Tomaz, Cândida T.

doi:10.1016/j.cytogfr.2017.11.005

Cited by 50 publications

(39 citation statements)

References 114 publications

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“…As shown in Fig. 8b , the ischemia-induced elevation of PLGF [ 13 ] was also significantly blunted when ischemic retinas were pre-administrated with the VEGF trap/anti-PLGF Eylea. This is similar to the effect of 1.0 g/Kg/day of DNL.…”

Section: Discussionmentioning

confidence: 97%

“…Upregulation of HIF-1α and VEGF has also be observed in the Norrin depleted retina [ 5 ]. In addition to VEGF [ 8 , 10 , 12 ], placental growth factor (PLGF) has been reported to be increased when there are defined ischemic disorders of the retina/choroid vasculature; thus, downregulation of this factor is able to be utilized as a biomarker for visual functional outcome and treatment [ 13 ]. The present study aims to provide further confirmation regarding these ischemic alterations.…”

Section: Introductionmentioning

confidence: 99%

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Dendrobium nobile Lindley and its bibenzyl component moscatilin are able to protect retinal cells from ischemia/hypoxia by dowregulating placental growth factor and upregulating Norrie disease protein

Chao¹,

Lai²,

Pan³

et al. 2018

BMC Complement Altern Med

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BackgroundPresumably, progression of developmental retinal vascular disorders is mainly driven by persistent ischemia/hypoxia. An investigation into vision-threatening retinal ischemia remains important. Our aim was to evaluate, in relation to retinal ischemia, protective effects and mechanisms of Dendrobium nobile Lindley (DNL) and its bibenzyl component moscatilin. The therapeutic mechanisms included evaluations of levels of placental growth factor (PLGF) and Norrie disease protein (NDP).MethodsAn oxygen glucose deprivation (OGD) model involved cells cultured in DMEM containing 1% O2, 94% N2 and 0 g/L glucose. High intraocular pressure (HIOP)-induced retinal ischemia was created by increasing IOP to 120 mmHg for 60 min in Wistar rats. The methods included electroretinogram (ERG), histopathology, MTT assay and biochemistry.ResultsWhen compared with cells cultured in DMEM containing DMSO (DMSO+DMEM), cells subjected to OGD and pre-administrated with DMSO (DMSO+OGD) showed a significant reduction in the cell viability and NDP expression. Moreover, cells that received OGD and 1 h pre-administration of 0.1 μM moscatilin (Pre-OGD Mos 0.1 μM) showed a significant counteraction of the OGD-induced decreased cell viability. Furthermore, compared with the DMSO+OGD group (44.54 ± 3.15%), there was significant elevated NDP levels in the Pre-OGD Mos 0.1 μM group (108.38 ± 29.33%). Additionally, there were significant ischemic alterations, namely reduced ERG b-wave, less numerous retinal ganglion cells, decreased inner retinal thickness, and reduced/enhanced amacrine’s ChAT/Müller’s GFAP or vimentin immunolabelings. Moreover, there were significantly increased protein levels of HIF-1α, VEGF, PKM2, RBP2 and, particularly, PLGF (pg/ml; Sham vs. Vehicle: 15.11 ± 1.58 vs. 39.53 ± 5.25). These ischemic effects were significantly altered when 1.0 g/Kg/day DNL (DNL1.0 + I/R or I/R+ DNL1.0) was applied before and/or after ischemia, but not vehicle (Vehicle+I/R). Of novelty and significance, the DNL1.0 action mechanism appears to be similar to that of the anti-PLGF Eylea [PLGF (pg/ml); DNL1.0 vs. Eylea+I/R: 19.93 ± 2.24 vs. 6.44 ± 0.60].ConclusionsDNL and moscatilin are able to protect against retinal ischemic/hypoxic changes respectively by downregulating PLGF and upregulating NDP. Progression of developmental retinal vascular disorders such as Norrie disease due to persistent ischemia/hypoxia might be thus prevented.Electronic supplementary materialThe online version of this article (10.1186/s12906-018-2256-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Dendrobium nobile Lindley and its bibenzyl component moscatilin are able to protect retinal cells from ischemia/hypoxia by dowregulating placental growth factor and upregulating Norrie disease protein

Chao¹,

Lai²,

Pan³

et al. 2018

BMC Complement Altern Med

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“…The physiological functions of endothelial VEGFR1 signaling, activated by VEGFA, VEGFB, or PlGF, are assumed to be negligible, because mice that lack the intracellular kinase domain of VEGFR1 are viable and have no vascular abnormalities [ 57 ]. Conversely, the VEGFR1 signal in monocytes and macrophages contributes significantly under inflammatory conditions [ 58 ], correlating with the upregulation of VEGFB and PlGF in eyes with DR [ 59 ].…”

Section: Pathophysiology Of Diabetic Retinopathymentioning

confidence: 99%

Pathophysiology of Diabetic Retinopathy: The Old and the New

et al. 2018

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Vision loss in diabetic retinopathy (DR) is ascribed primarily to retinal vascular abnormalities—including hyperpermeability, hypoperfusion, and neoangiogenesis—that eventually lead to anatomical and functional alterations in retinal neurons and glial cells. Recent advances in retinal imaging systems using optical coherence tomography technologies and pharmacological treatments using anti-vascular endothelial growth factor drugs and corticosteroids have revolutionized the clinical management of DR. However, the cellular and molecular mechanisms underlying the pathophysiology of DR are not fully determined, largely because hyperglycemic animal models only reproduce limited aspects of subclinical and early DR. Conversely, non-diabetic mouse models that represent the hallmark vascular disorders in DR, such as pericyte deficiency and retinal ischemia, have provided clues toward an understanding of the sequential events that are responsible for vision-impairing conditions. In this review, we summarize the clinical manifestations and treatment modalities of DR, discuss current and emerging concepts with regard to the pathophysiology of DR, and introduce perspectives on the development of new drugs, emphasizing the breakdown of the blood-retina barrier and retinal neovascularization.

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“…Physiological angiogenesis is highly regulated during wound repair [17,18]. Pathological choroidal and retinal angiogenesis are the leading causes of blindness, including age-related macular degeneration and diabetic retinopathy [19,20]. In angiogenesis, a serial process participated with several cells that include proteolytic degradation of the extracellular matrix, followed by migration and proliferation of capillary endothelial cells, pericyte recruitment, and assembly of the mature vessel [21].…”

Section: Discussionmentioning

confidence: 99%

The Inhibitory Effects of Gold Nanoparticles on VEGF-A-Induced Cell Migration in Choroid-Retina Endothelial Cells

Chan

Hsiao

et al. 2019

IJMS

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Background: Vascular endothelial growth factor (VEGF) is upregulated by hypoxia and is a crucial stimulator for choroidal neovascularization (CNV) in age-related macular degeneration and pathologic myopia, as well as retinal neovascularization in proliferative diabetic retinopathy. Retinal and choroidal endothelial cells play key roles in the development of retinal and CNV, and subsequent fibrosis. At present, the effects of gold nanoparticles (AuNPs) on the VEGF-induced choroid-retina endothelial (RF/6A) cells are still unknown. In our study, we investigated the effects of AuNPs on RF/6A cell viabilities and cell adhesion to fibronectin, a major ECM protein of fibrovascular membrane. Furthermore, the inhibitory effects of AuNPs on RF/6A cell migration induced by VEGF and its signaling were studied. Methods: The cell viability assay was used to determine the viability of cells treated with AuNPs. The migration of RF/6A cells was assessed by the Transwell migration assay. The cell adhesion to fibronectin was examined by an adhesion assay. The VEGF-induced signaling pathways were determined by western blotting. Results: The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay revealed no cytotoxicity of AuNPs on RF/6A cells. AuNPs inhibited VEGF-induced RF/6A cell migration in a concentration-dependent manner but showed no significant effects on RF/6A cell adhesion to fibronectin. Inhibitory effects of AuNPs on VEGF-induced Akt/eNOS were found. Conclusions: These results suggest that AuNPs are an effective inhibitor of VEGF-induced RF/6A cell migration through the Akt/eNOS pathways, but they have no effects on their cell viabilities and cell adhesion to fibronectin.

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Vascular endothelial growth factors and placenta growth factor in retinal vasculopathies: Current research and future perspectives

Cited by 50 publications

References 114 publications

Dendrobium nobile Lindley and its bibenzyl component moscatilin are able to protect retinal cells from ischemia/hypoxia by dowregulating placental growth factor and upregulating Norrie disease protein

Dendrobium nobile Lindley and its bibenzyl component moscatilin are able to protect retinal cells from ischemia/hypoxia by dowregulating placental growth factor and upregulating Norrie disease protein

Pathophysiology of Diabetic Retinopathy: The Old and the New

The Inhibitory Effects of Gold Nanoparticles on VEGF-A-Induced Cell Migration in Choroid-Retina Endothelial Cells

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