scholarly journals Inhibition of Ocular Neovascularization by Co-Inhibition of VEGF-A and PLGF

2015 ◽  
Vol 35 (5) ◽  
pp. 1787-1796 ◽  
Author(s):  
Xiaochuan Huo ◽  
Youxiang Li ◽  
Yuhua Jiang ◽  
Xiaoyun Sun ◽  
Lixue Gu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Angiogenic Factors ◽  
Vessel Density ◽  
Age Related Macular Degeneration ◽  
Ocular Injury ◽  
Age Related

Background/Aims: Age-related macular degeneration (AMD) appears to be a disease with increasing incidence in Western countries and may develop into acquired blindness. Choroidal neovascularization (CNV) is the most frequent cause for AMD, and is commonly induced by regional inflammation. Past studies have highlighted vascular endothelial growth factor A (VEGF-A) as a major trigger for CNV. However, studies on the associated angiogenic factors other than VEGF-A are lacking. Methods: Here, we used a well-established laser burn (LB)-induced experimental CNV mouse model to study the molecular mechanisms underlying the development of CNV after ocular injury. We analyzed vessel density by lectin labeling. We isolated macrophages, endothelial cells and other cell types by flow cytometry, and analyzed levels of different angiogenic factors in these populations. We used antisera against VEGF-A (aVEGF) and/or antisera against placental growth factor (PLGF; aPLGF) to antagonize CNV. We used an antibody-driven toxin to selectively eliminate macrophages to evaluate the role of macrophages in CNV. We also examined expression of PLGF in macrophage subtypes. Results: The choroidal vessel density increased significantly 7 days after LB. LB increased significantly the levels of VEGF-A and PLGF in mouse eyes. Treatment with aVEGF significantly blunted increases in vessel density by LB. Treatment with aPLGF alone did not significantly reduce increases in vessel density. However, aPLGF significantly increased the inhibitory effects of aVEGF on vessel density increases. While VEGF-A was produced by endothelial cells, macrophages and other types at similar levels, PLGF seemed to be predominantly produced by macrophages. Selective macrophage depletion significantly reduced CNV. M2, but M1 macrophages produced high levels of PLGF. Conclusions: Together, our data suggest a previously unappreciated role of PLGF in coordination with VEGF-A to regulate CNV during ocular injury. Our study highlights macrophages and their production of PLGF as novel targets for CNV therapy.

scholarly journals Endothelial-to-Mesenchymal Transition (EndoMT): Roles in Tumorigenesis, Metastatic Extravasation and Therapy Resistance

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Valentin Platel ◽  
Sébastien Faure ◽  
Isabelle Corre ◽  
Nicolas Clere
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Cell Types ◽  
Therapy Resistance ◽  
Experimental Conditions ◽  
Potential Implication ◽  
Mesenchymal Transition ◽  
Endothelial To Mesenchymal Transition

Cancer cells evolve in a very complex tumor microenvironment, composed of several cell types, among which the endothelial cells are the major actors of the tumor angiogenesis. Today, these cells are also characterized for their plasticity, as endothelial cells have demonstrated their potential to modify their phenotype to differentiate into mesenchymal cells through the endothelial-to-mesenchymal transition (EndoMT). This cellular plasticity is mediated by various stimuli including transforming growth factor-β (TGF-β) and is modulated dependently of experimental conditions. Recently, emerging evidences have shown that EndoMT is involved in the development and dissemination of cancer and also in cancer cell to escape from therapeutic treatment. In this review, we summarize current updates on EndoMT and its main induction pathways. In addition, we discuss the role of EndoMT in tumorigenesis, metastasis, and its potential implication in cancer therapy resistance.

scholarly journals Inflammatory Mediators and Angiogenic Factors in Choroidal Neovascularization: Pathogenetic Interactions and Therapeutic Implications

2010 ◽  
Vol 2010 ◽  
pp. 1-14 ◽  
Author(s):  
Claudio Campa ◽  
Ciro Costagliola ◽  
Carlo Incorvaia ◽  
Carl Sheridan ◽  
Francesco Semeraro ◽  
...  
Keyword(s):  
Growth Factor ◽  
Choroidal Neovascularization ◽  
Inflammatory Mediators ◽  
Transforming Growth Factor ◽  
Pathological Condition ◽  
Inflammatory Cells ◽  
Angiogenic Factors ◽  
Age Related Macular Degeneration ◽  
Therapeutic Implications ◽  
Age Related

Choroidal neovascularization (CNV) is a common and severe complication in heterogeneous diseases affecting the posterior segment of the eye, the most frequent being represented by age-related macular degeneration. Although the term may suggest just a vascular pathological condition, CNV is more properly definable as an aberrant tissue invasion of endothelial and inflammatory cells, in which both angiogenesis and inflammation are involved. Experimental and clinical evidences show that vascular endothelial growth factor is a key signal in promoting angiogenesis. However, many other molecules, distinctive of the inflammatory response, act as neovascular activators in CNV. These include fibroblast growth factor, transforming growth factor, tumor necrosis factor, interleukins, and complement. This paper reviews the role of inflammatory mediators and angiogenic factors in the development of CNV, proposing pathogenetic assumptions of mutual interaction. As an extension of this concept, new therapeutic approaches geared to have an effect on both the vascular and the extravascular components of CNV are discussed.

scholarly journals A review of the multifunctionality of angiopoietin-like 4 in eye disease

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Xinyue Yang ◽  
Yan Cheng ◽  
Guanfang Su
Keyword(s):  
Molecular Mechanisms ◽  
Age Related Macular Degeneration ◽  
Eye Disease ◽  
Future Research ◽  
Potential Therapeutic Target ◽  
Vein Occlusion ◽  
Age Related ◽  
Functional Mechanisms ◽  
Multifunctional Cytokine

Angiopoietin-like protein 4 (ANGPTL4) is a multifunctional cytokine regulating vascular permeability, angiogenesis, and inflammation. Dysregulations in these responses contribute to the pathogenesis of ischemic retinopathies such as diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal vein occlusion, and sickle cell retinopathy (SCR). However, the role of ANGPTL4 in these diseases remains controversial. Here, we summarize the functional mechanisms of ANGPTL4 in several diseases. We highlight original studies that provide detailed data about the mechanisms of action for ANGPTL4, its applications as a diagnostic or prognostic biomarker, and its use as a potential therapeutic target. Taken together, the discussions in this review will help us gain a better understanding of the molecular mechanisms by which ANGPTL4 functions in eye disease and will provide directions for future research.

scholarly journals Association of Blood Group Antigen CD59 with Disease

2022 ◽  
pp. 1-12
Author(s):  
Christof Weinstock
Keyword(s):  
Blood Group ◽  
Cell Clone ◽  
Membrane Attack Complex ◽  
Cell Types ◽  
Blood Group Antigen ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Life Threatening ◽  
Membrane Bound

In 2014, the membrane-bound protein CD59 became a blood group antigen. CD59 has been known for decades as an inhibitor of the complement system, located on erythrocytes and on many other cell types. In paroxysmal nocturnal haemoglobinuria (PNH), a stem cell clone with acquired deficiency to express GPI-anchored molecules, including the complement inhibitor CD59, causes severe and life-threatening disease. The lack of CD59, which is the only membrane-bound inhibitor of the membrane attack complex, contributes a major part of the intravascular haemolysis observed in PNH patients. This crucial effect of CD59 in PNH disease prompted studies to investigate its role in other diseases. In this review, the role of CD59 in inflammation, rheumatic disease, and age-related macular degeneration is investigated. Further, the pivotal role of CD59 in PNH and congenital CD59 deficiency is reviewed.

scholarly journals HGF and VEGF-A and Their Receptors Show Expression and Angiogenic Effects on Human Choroidal Endothelial Cells: Implications for Treatments of Neovascular Age-Related Macular Degeneration

2021 ◽  
Vol 1 (1) ◽  
pp. 69-82
Author(s):  
Elizabeth A. Stewart ◽  
Claire L. Allen ◽  
Govindi J. Samaranayake ◽  
Thomas Stubington ◽  
Rukhsar Akhtar ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
In Vitro Assays ◽  
Prolonged Treatment ◽  
Vegf Receptor ◽  
Tubule Formation ◽  
Age Related ◽  
And Migration

Intraocular neovascularisation is associated with common blinding conditions including neovascular age-related macular degeneration (nAMD). Vascular endothelial growth factor (VEGF) is central in driving choroidal neovascularisation in this disease. Many clinical therapies target VEGF-A with intravitreal anti-VEGF drugs, which, however, have limited efficacy and require repeated, prolonged treatment. Other cytokines are known to be involved, including hepatocyte growth factor (HGF), which is shown to have a role in the early stages of nAMD. We investigated the effect of HGF and its co-operation with VEGF-A on human choroidal endothelial cells (CEC). The expression of HGF and related molecules in CEC was investigated using immunofluorescence, Western blotting and flow cytometry. In vitro assays for proliferation, tubule formation and migration were used to assess the potential role of HGF in neovascularisation. Primary human CEC expressed HGF, VEGF-A and their receptors MET and VEGF receptor 2 (VEGFR2). HGF increased CEC proliferation, tubule formation and migration; the increased proliferation and migration appeared to be additive with that achieved with VEGF-A. This study provides insight into growth factor co-operation in CEC signalling and indicates that simultaneous blockage of multiple growth factors or common downstream signalling pathways may provide a more sustained treatment response, enhancing treatments in nAMD.

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