Aqueous humor levels of vascular endothelial growth factor and adiponectin in patients with type 2 diabetes before and after intravitreal bevacizumab injection

Costagliola, Ciro; Daniele, Aurora; dell’Omo, Roberto; Romano, Mario R.; Aceto, Fabiana; Agnifili, Luca; Semeraro, Francesco; Porcellini, Antonio

doi:10.1016/j.exer.2013.02.004

Cited by 34 publications

(30 citation statements)

References 37 publications

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“…Also, a significant correction was established between vitreous EPO and blood glucose in patients with PDR [41]. Moreover, adiponectin (APN) levels were markedly increased in aqueous humor obtained from PDR patients, and significantly decreased after injection of bevacizumab [42]. All these mediators may be potential targets in PDR treatment.…”

Section: Discussionmentioning

confidence: 99%

Identification of Chemokines and Growth Factors in Proliferative Diabetic Retinopathy Vitreous

Dai

Wang

et al. 2014

BioMed Research International

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Associations were investigated between levels of chemokines and growth factors in the vitreous and proliferative diabetic retinopathy (PDR). Enrolled were 58 patients (58 eyes) requiring pars plana vitrectomy (PPV), with PDR (n = 32, none with traction retinal detachment) or not (non-PDR). In the latter, 16 had macular hole (MH) and 10 had epiretinal membrane (ERM). With a multiplex bead immunoassay, levels of 11 chemokines and growth factors were measured from the undiluted vitreous sample from each patient. In the non-PDR eyes, the levels of the 11 chemokines and growth factors tested were similar between patients with MH and those with ERM. However, the levels of all 11 were significantly higher in the PDR eyes relative to the non-PDR; CCL17, CCL19, and TGFβ3 were markedly upregulated and have not been investigated in PDR previously. The significantly higher levels of CCL4 and CCL11 in PDR contradict the results of previous reports. Based on Spearman's nonparametric test, moderate-to-strong correlations were found between VEGF and other mediators. Our results indicate that these chemokines and growth factors could be candidates for research into targeted therapies applied either singly or in combination with anti-VEGF drugs for the treatment of PDR.

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Section: Discussionmentioning

confidence: 99%

Identification of Chemokines and Growth Factors in Proliferative Diabetic Retinopathy Vitreous

Dai

Wang

et al. 2014

BioMed Research International

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“…Additionally, hypoadiponectinemia is positively correlated with the severity of retinopathy in T2DM [122]. Recently, Costagliola et al analyzed the levels of vascular endothelial growth factor (VEGF) and adiponectin in the aqueous humor of patients with diabetic proliferative retinopathy (PDR) and found that they were significantly higher than those recorded in control subjects [123, 124]. A possible explanation of this finding may be attributed to the increased blood retinal barrier permeability documented in PDR patients [125].…”

Section: Adiponectin and Obesity-related Diseasesmentioning

confidence: 99%

“…Another possible explanation could be the local reparative response to endothelial dysfunction; in fact, adiponectin induces endothelial nitric oxide production in vitro [126]. Moreover, intravitreal bevacizumab, an angiogenesis inhibitor, significantly reduced the levels of VEGF and adiponectin [123]. The treatment with anti-VEGF agents as bevacizumab significantly reduced macular edema and it is possible that bevacizumab also modulates mediators involved in the pathogenesis of macular edema as adiponectin.…”

Section: Adiponectin and Obesity-related Diseasesmentioning

confidence: 99%

New Insight into Adiponectin Role in Obesity and Obesity-Related Diseases

Nigro

Scudiero

Monaco

et al. 2014

BioMed Research International

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485

364

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Obesity is a major health problem strongly increasing the risk for various severe related complications such as metabolic syndrome, cardiovascular diseases, respiratory disorders, diabetic retinopathy, and cancer. Adipose tissue is an endocrine organ that produces biologically active molecules defined “adipocytokines,” protein hormones with pleiotropic functions involved in the regulation of energy metabolism as well as in appetite, insulin sensitivity, inflammation, atherosclerosis, cell proliferation, and so forth. In obesity, fat accumulation causes dysregulation of adipokine production that strongly contributes to the onset of obesity-related diseases. Several advances have been made in the treatment and prevention of obesity but current medical therapies are often unsuccessful even in compliant patients. Among the adipokines, adiponectin shows protective activity in various processes such as energy metabolism, inflammation, and cell proliferation. In this review, we will focus on the current knowledge regarding the protective properties of adiponectin and its receptors, AdipoRs (“adiponectin system”), on metabolic complications in obesity and obesity-related diseases. Adiponectin, exhibiting antihyperglycemic, antiatherogenic, and anti-inflammatory properties, could have important clinical benefits in terms of development of therapies for the prevention and/or for the treatment of obesity and obesity-related diseases.

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“…Similar mechanisms have been proposed for metalloproteinases 78 and ATP. 79 Any stretch-induced VEGF production would be superimposed on background levels already present within aqueous humor (reported to be between 15 and 533 pg/ml 80–88 ). VEGF levels also are subject to binding to heparin sulfate proteoglycans and may be affected by several factors, including TGF-β2, 18 BMP-7, 18 hypoxia, 89 as well as additional VEGF secretion by any macrophages 90 that may be present within the TM.…”

Section: Discussionmentioning

confidence: 99%

VEGF as a Paracrine Regulator of Conventional Outflow Facility

Reina-Torres

Wen

Liu

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PurposeVascular endothelial growth factor (VEGF) regulates microvascular endothelial permeability, and the permeability of Schlemm's canal (SC) endothelium influences conventional aqueous humor outflow. We hypothesize that VEGF signaling regulates outflow facility.MethodsWe measured outflow facility (C) in enucleated mouse eyes perfused with VEGF-A164a, VEGF-A165b, VEGF-D, or inhibitors to VEGF receptor 2 (VEGFR-2). We monitored VEGF-A secretion from human trabecular meshwork (TM) cells by ELISA after 24 hours of static culture or cyclic stretch. We used immunofluorescence microscopy to localize VEGF-A protein within the TM of mice.ResultsVEGF-A164a increased C in enucleated mouse eyes. Cyclic stretch increased VEGF-A secretion by human TM cells, which corresponded to VEGF-A localization in the TM of mice. Blockade of VEGFR-2 decreased C, using either of the inhibitors SU5416 or Ki8751 or the inactive splice variant VEGF-A165b. VEGF-D increased C, which could be blocked by Ki8751.ConclusionsVEGF is a paracrine regulator of conventional outflow facility that is secreted by TM cells in response to mechanical stress. VEGF affects facility via VEGFR-2 likely at the level of SC endothelium. Disruption of VEGF signaling in the TM may explain why anti-VEGF therapy is associated with decreased outflow facility and sustained ocular hypertension.

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Aqueous humor levels of vascular endothelial growth factor and adiponectin in patients with type 2 diabetes before and after intravitreal bevacizumab injection

Cited by 34 publications

References 37 publications

Identification of Chemokines and Growth Factors in Proliferative Diabetic Retinopathy Vitreous

Identification of Chemokines and Growth Factors in Proliferative Diabetic Retinopathy Vitreous

New Insight into Adiponectin Role in Obesity and Obesity-Related Diseases

VEGF as a Paracrine Regulator of Conventional Outflow Facility

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