Prodrug of epigallocatechin-3-gallate alleviates choroidal neovascularization via down-regulating HIF-1α/VEGF/VEGFR2 pathway and M1 type macrophage/microglia polarization

Xu, Jiaowen; Tu, Yuanyuan; Wang, Ying; Xu, Xun; Sun, Xiaodong; Xie, Laiqing; Zhao, Qingliang; Yang, Guo; Gu, Yong-Hui; Du, Jingxia; Du, Shu; Zhu, Manhui; Song, E

doi:10.1016/j.biopha.2019.109606

Cited by 35 publications

(10 citation statements)

References 35 publications

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“…In CNV formation, VEGF induces the proliferation of vascular endothelial cells and promotes macrophage migration [ 212 ]. Macrophages/microglia which infiltrate the CNV regions secrete IL-6 and TNF-α, and the attenuation of macrophage migration by blocking CCL2 and downregulating the HIF-1α/VEGF pathway suppresses the leakage and reduce the area of laser-induced CNV, a widely used animal model of neovascular AMD [ 213 , 214 ]. Surgically removed human CNV membranes also indicated that TNF-α derived from macrophages facilitates pathologic angiogenesis in AMD [ 215 ].…”

Section: Pathology Of Age-related Macular Degeneration (Amd) and Imentioning

confidence: 99%

Protective Effects and Molecular Signaling of n-3 Fatty Acids on Oxidative Stress and Inflammation in Retinal Diseases

2020

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Oxidative stress and inflammation play crucial roles in the development and progression of retinal diseases. Retinal damage by various etiologies can result in retinopathy of prematurity (ROP), diabetic retinopathy (DR), and age-related macular degeneration (AMD). n-3 fatty acids are essential fatty acids and are necessary for homeostasis. They are important retinal membrane components and are involved in energy storage. n-3 fatty acids also have antioxidant and anti-inflammatory properties, and their suppressive effects against ROP, DR, and AMD have been previously evaluated. α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and their metabolites have been shown to alleviate retinal oxidative stress and inflammation involving various biological signaling pathways. In this review, we summarize the current understanding of the n-3 fatty acids effects on the mechanisms of these retinal diseases and how they exert their therapeutic effects, focusing on ALA, EPA, DHA, and their metabolites. This knowledge may provide new remedial strategies for n-3 fatty acids in the prevention and treatment of retinal diseases associated with oxidative stress and inflammation.

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Section: Pathology Of Age-related Macular Degeneration (Amd) and Imentioning

confidence: 99%

Protective Effects and Molecular Signaling of n-3 Fatty Acids on Oxidative Stress and Inflammation in Retinal Diseases

2020

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“… 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%

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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“…[165][166][167][168][169] Previous studies also showed that CNV could be inhibited by downregulating M1 macrophage/microglia polarization. 170 Allingham et al suggested that the early recruitment of inflammatory M1 macrophages promoted the induction and initial development of CNV, followed by the sustained recruitment of reparative M2 macrophages that mediated the sustained CNV formation and growth. 160 ALEs are found in drusen and Bruch's membrane of AMD patients, and act as haptens to induce autoantibody formation against lipid peroxide-modified retinal proteins, causing inflammatory responses and complement activation, and damaging the RPE cells.…”

Section: Lcpufa Peroxidation and Its Effects On Inflammation In Amdmentioning

confidence: 99%

Long-Chain Polyunsaturated Fatty Acids and Their Metabolites Regulate Inflammation in Age-Related Macular Degeneration

Ren¹,

Ren²,

Deng³

et al. 2022

JIR

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Age-related macular degeneration (AMD) is a blinding eye disease, whose incidence strongly increases with ages. The etiology of AMD is complex, including aging, abnormal lipid metabolism, chronic inflammation and oxidative stress. Long-chain polyunsaturated fatty acids (LCPUFA) are essential for ocular structures and functions. This review summarizes the regulatory effects of LCPUFA on inflammation in AMD. LCPUFA are related to aging, autophagy and chronic inflammation. They are metabolized to pro-and anti-inflammatory metabolites by various enzymes. These metabolites stimulate inflammation in response to oxidative stress, causing innate and acquired immune responses. This review also discusses the possible clinical applications, which provided novel targets for the prevention and treatment of AMD and other age-related diseases.

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Prodrug of epigallocatechin-3-gallate alleviates choroidal neovascularization via down-regulating HIF-1α/VEGF/VEGFR2 pathway and M1 type macrophage/microglia polarization

Cited by 35 publications

References 35 publications

Protective Effects and Molecular Signaling of n-3 Fatty Acids on Oxidative Stress and Inflammation in Retinal Diseases

Protective Effects and Molecular Signaling of n-3 Fatty Acids on Oxidative Stress and Inflammation in Retinal Diseases

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

Long-Chain Polyunsaturated Fatty Acids and Their Metabolites Regulate Inflammation in Age-Related Macular Degeneration

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