Mineralocorticoid receptor antagonism limits experimental choroidal neovascularization and structural changes associated with neovascular age-related macular degeneration

Zhao, Min; Mantel, Irmela; Gélizé, Emmanuelle; Li, Xinxin; Xie, Xiaoyue; Arboleda, Alejandro; Séminel, Marie; Levy-Boukris, Rinath; Dernigoghossian, Marilyn; Prunotto, Andrea; Andrieu-Soler, Charlotte; Rivolta, Carlo; Canonica, Jérémie; Naud, Marie‐Christine; Lechner, Sebastian M.; Farman, Nicolette; Bravo‐Osuna, Irene; Herrero–Vanrell, R.; Jaisser, Frédéric; Behar‐Cohen, Francine

doi:10.1038/s41467-018-08125-6

Cited by 51 publications

(45 citation statements)

References 68 publications

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“… 4 – 6 Choroidal neovascularization (CNV) deriving from the choriocapillaris toward the retinal neurosensory layer underneath the macula can cause retinal pigment epithelium (RPE) and Bruch’s membrane breakdown, and subretinal bleb detachment bleeding. 7 During pathogenesis of CNV, ischemia and hy-poxia induce the expression of hypoxia-inducible factor-1α (HIF-1α), which transcribes vascular endothelial growth factor (VEGF). 7 , 8 Overexpres-sion of VEGF plays a central role in CNV growth.…”

Section: Introductionmentioning

confidence: 99%

“… 7 During pathogenesis of CNV, ischemia and hy-poxia induce the expression of hypoxia-inducible factor-1α (HIF-1α), which transcribes vascular endothelial growth factor (VEGF). 7 , 8 Overexpres-sion of VEGF plays a central role in CNV growth. Before anti-VEGF drug clinical application, Verteporfin photodynamic therapy (PDT) was the main approach for CNV treatment.…”

Section: Introductionmentioning

confidence: 99%

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Comparative efficacy and safety of anti-vascular endothelial growth factor regimens for neovascular age-related macular degeneration: systematic review and Bayesian network meta-analysis

Zhao

Wang

et al. 2020

Therapeutic Advances in Chronic Disease

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Background: As a debilitating neurodegenerative disease, neovascular age-related macular degeneration (nAMD) accounts for more than 90% of severe visual loss or legal blindness among AMD patients. Anti-vascular endothelial growth factor (VEGF) had been applied widely in nAMD treatment. To date, debate regarding efficacy and safety still exists among different anti-VEGF regimens as management of nAMD. To provide substantial evidence for clinical nAMD treatment, this study ranks the priority of anti-VEGF regimens via Bayesian network meta-analysis (NMA), comparing data collected from randomized controlled trials (RCTs). Methods: We searched PubMed Central, MEDLINE Ovid, Embase Ovid, ISRCTN, ICTRP and ClinicalTrials. gov from a database established until 1 April 2019 systematically for anti-VEGF regimens. Bayesian NMA with random-effect was conducted to compare efficacy and safety and rank priority of anti-VEGF regimens. The primary efficacy and safety outcomes were the proportion of patients gaining 15 or more letters, and the incidence of arterial thromboembolic (ATC) events. The effect measure is the standard mean difference (SMD), or the odds ratio (OR) with their 95% confidence interval (CI). The study protocol is registered with PROSPERO, number CRD42019132243. Results: We obtained 6467 citations and identified 29 RCTs including 13,596 participants; 86% of these trials were low risk or of uncertain risk bias. In NMA, ORs compared with sham injection for the proportion of patients gaining 15 or more letters (12,699 participants from 23 trials) ranged from 4.05 [95% Bayesian credible interval (CrI) 1.62–10.11] for ranibizumab quarterly regimen to 8.57 (95% CrI 4.66–15.73) for a ranibizumab treat-and-extend regimen. No difference was found between sham injection and anti-VEGF regimens for ATC events (11,500 participants from 18 trials). Results for the primary outcome did not substantially change in sensitivity analyses after removing studies at high risk of bias and small sample size ( n < 100), respectively. Conclusion: The treat-and-extend regimen of ranibizumab and aflibercept are the preferred anti-VEGF regimens for nAMD. Bevacizumab treat-and-extend regimens need more head-to-head comparisons with other regimens or sham injection for advanced application. The treat-and-extend regimen proved to be the most effective regimen for each anti-VEGF drug in the NMA. Pegaptanib every 6 weeks and Conbercept quarterly are unable to satisfy the best corrected visual acuity (BCVA) improvement requirement of nAMD patients.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparative efficacy and safety of anti-vascular endothelial growth factor regimens for neovascular age-related macular degeneration: systematic review and Bayesian network meta-analysis

Zhao

Wang

et al. 2020

Therapeutic Advances in Chronic Disease

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“…Choroidal neovascularization (CNV) is the main cause of vision impairment in age-related macular degeneration (AMD), and AMD has become one of the main causes of blindness worldwide 1,2. Several factors may trigger CNV, such as vascular endothelial growth factor (VEGF), angiopoietin, basic fibroblast growth factor, and adhesion molecule (AM).…”

Section: Introductionmentioning

confidence: 99%

<p>Anti-Angiogenic Activity Of Bevacizumab-Bearing Dexamethasone-Loaded PLGA Nanoparticles For Potential Intravitreal Applications</p>

Liu

Zhang

et al. 2019

IJN

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PurposeAge-related macular degeneration is a multifactorial disease involving inflammation and choroidal neovascularization. Vascular endothelial growth factor (VEGF) has been regarded as a potential therapeutic target to treat choroidal neovascularization. Dexamethasone can interfere with the expression or action of VEGF while bevacizumab targets and combines with VEGF. We propose electrostatically-conjugated bevacizumab-bearing dexamethasone-loaded poly (D,L-lactide-co-glycolide)/polyethylenimine nanoparticles (eBev-DPPNs) for angiogenic combination treatment of ocular diseases.MethodsWe prepared a novel nanoparticle composed of poly (D, L-lactide-co-glycolide) and polyethylenimine and loaded the nanoparticles with dexamethasone. Bevacizumab was adsorbed onto the surfaces of the nanoparticles by electrostatic interactions. The eBev-DPPNs were evaluated according to their size, polydispersity index, zeta potential, morphology, drug loading, release behavior, and stability. The structural stability of bevacizumab on the surface of the nanoparticles was also analyzed. Subsequently, angiogenesis was investigated in the presence of the eBev-DPPNs using cell apoptosis, wound healing, Transwell invasion, and tube formation assays on the human umbilical vein endothelial cells (HUVECs) in vitro and chick embryo chorioallantoic membrane assay in vivo. The eBev-DPPNs intravitreal injection was applied in the laser-induced rabbit choroidal neovascularization (CNV) model to confirm the role for potential intravitreal applications.ResultsThe eBev-DPPNs was about 200 nm in diameter, with a narrow diameter distribution, and the surface charge was neutral (0.85 ± 0.37mV), which made the eBev-DPPNs stable under physiological conditions. The apoptosis, migration, invasion, and tube formation assays showed that the eBev-DPPNs had a good anti-angiogenic effect on HUVECs. The eBev-DPPNs also provided a strong inhibitory effect on VEGF secretion from HUVECs. Moreover, in vivo chick embryo chorioallantoic membrane assay showed eBev-DPPNs greatly reduced the amount of blood vessels. The leakage area of CNV decreased in the eBev-DPPNs group on rabbit CNV model.ConclusionThe eBev-DPPNs are a promising novel anti-angiogenesis therapeutic for potential intravitreal applications such as age-related macular degeneration.

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“…Choroidal neovascularization (CNV) is formed by the proliferating vessels of choroidal capillaries extending to the cleft of the vitreous membrane. It can occur between the nerve retina and the retinal pigment epithelium, between the vitreous membrane and the retinal pigment epithelium, and between the retinal pigment epithelium and the choroid ( Philip et al, 2019 , Zhao et al, 2019 ). Many diseases affecting retinal pigmented epithelium-vitreous membrane-choroidal capillary can lead to the formation of CNV.…”

Section: Introductionmentioning

confidence: 99%

Establishing a mouse model of choroidal neovascularization to study the therapeutic effect of levotinib and its mechanism

Xin

Zhu

et al. 2020

Saudi Journal of Biological Sciences

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Objective To study the therapeutic effect and mechanism of levotinib on choroidal neovascularization (CNV) in mice. Methods 45 healthy C57BL/6 mice were selected and randomly divided into three groups: control group (group A), model group (group B) and levotinib group (group C). The model of CNV in mice was established. The fluorescence leakage of choroidal lesions in mice was observed by fundus fluorescein angiography. The morphological changes of retinal vessels in mice were observed by retinal slice preparation, the pathological changes of eyeball tissues in mice were observed by hematoxylin-eosin (HE) staining, the expression of vascular endothelial growth factor (VEGF) in mice retina was detected by real-time quantitative fluorescence PCR, and the protein expression of VEGF in mice retina was detected by Western blotting. Result On the 7th, 14th and 21st day after modeling, compared with group B, the fluorescence leakage area of group C mice was significantly reduced, and the difference was statistically significant (P < 0.05). The morphology of retinal vessels in group A was normal. In group B, the retinal vessels showed large areas of ischemia without perfusion and abundant neovascularization clusters and capillaries. Compared with group B, the morphology of retinal vessels in group C was significantly improved. Group A mice had normal eyeball structure, group B mice had visible spindle-like damage to the inner and outer retina, while group C mice had significantly less spindle-like damage than group B. Compared with group A, group B mice had significantly higher expression of retinal VEGF and the difference was statistically significant (P < 0.05), but compared with group B mice, the expression of VEGF in the retina of mice in group C was significantly decreased, and the difference was statistically significant (P < 0.05). Compared with group A, the expression of VEGF in retina of group B mice was significantly increased, and the difference was statistically significant (P < 0.05). Compared with group B, the expression of VEGF in retina of group C mice was significantly decreased, and the difference was statistically significant (P < 0.05). Conclusion Levatinib has obvious therapeutic effect on CNV, which may be achieved by inhibiting the high expression of VEGF in CNV.

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Mineralocorticoid receptor antagonism limits experimental choroidal neovascularization and structural changes associated with neovascular age-related macular degeneration

Cited by 51 publications

References 68 publications

Comparative efficacy and safety of anti-vascular endothelial growth factor regimens for neovascular age-related macular degeneration: systematic review and Bayesian network meta-analysis

Comparative efficacy and safety of anti-vascular endothelial growth factor regimens for neovascular age-related macular degeneration: systematic review and Bayesian network meta-analysis

<p>Anti-Angiogenic Activity Of Bevacizumab-Bearing Dexamethasone-Loaded PLGA Nanoparticles For Potential Intravitreal Applications</p>

Establishing a mouse model of choroidal neovascularization to study the therapeutic effect of levotinib and its mechanism

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