scholarly journals Role of vascular endothelial growth factor-165b in the breakdown of the blood-retinal barrier after acute high intraocular pressure in rats

2019 ◽  
Author(s):  
Jing Shen ◽  
Xi-Nan Yi ◽  
Zheng-Hai Liu ◽  
Min Li ◽  
Wei-Xian Liu ◽  
...  

Abstract Background: The blood-retinal barrier (BRB) is essential in maintaining the retinal homeostasis of the microenvironment, previous studies have found that BRB breakdown occurs after acute high intraocular pressure (HIOP) in rats, elevated intraocular pressure can induce upregulation of vascular endothelial growth factor-165b (VEGF-165b) protein in the retina, but the role of VEGF-A165b in BRB breakdown after acute HIOP is still undetermined. Methods: In this study, the rat acute HIOP model was established before and after intravitreous injection of anti-VEGF-165b antibody. The expression of VEGF-165b and ZO-1 in rat retina was detected by immunohistochemistry or western blotting, and the breakdown of BRB was detected by Evans blue (EB) dye. Results: The normal retina of rats expressed VEGF-165b protein, which was mainly located in the retinal ganglion cell (RGC) layer and the inner nuclear layer and was coexpressed with tight junction protein ZO-1. After acute HIOP, the expression of VEGF-165b was upregulated (P < 0.01); The expression of ZO-1 was downregulated (P < 0.01) at 12 h and then recovered at 3 d; EB leakage increased, peaking at 12 h (P < 0.01). After intravitreous injection of anti-VEGF-165b antibody, the expression of VEGF-165b protein was significantly downregulated (P < 0.01); and the downregulation of the expression of ZO-1 was more obvious (P < 0.01); EB leakage became more serious, peaking at 3 d (P < 0.01). EB analysis also showed that EB leakage in the peripheral retina was greater than that in the central retina (P < 0.01). Conclusions: The endogenous VEGF-165b protein may protect the BRB from acute HIOP by regulating the expression of ZO-1. The differential destruction of BRB after acute HIOP may be related to the selective loss of RGCs.

2008 ◽  
Vol 2008 ◽  
pp. 1-6 ◽  
Author(s):  
Seung-Ah Yoo ◽  
Seung-Ki Kwok ◽  
Wan-Uk Kim

Recent experimental and clinical studies have placed new emphasis on the role of angiogenesis in chronic inflammatory disease. Vascular endothelial growth factor (VEGF) and its receptors are the best characterized system in the regulation of rheumatoid arthritis (RA) by angiogenesis. Furthermore, in addition to its angiogenic role, VEGF can act as a direct proinflammatory mediator during the pathogenesis of RA, and protect rheumatoid synoviocytes from apoptosis, which contributes to synovial hyperplasia. Therefore, the developments of synovial inflammation, hyperplasia, and angiogenesis in the joints of RA patients seem to be regulated by a common cue, namely, VEGF. Agents that target VEGF, such as anti-VEGF antibody and aptamer, have yielded promising clinical data in patients with cancer or macular degeneration, and in RA patients, pharmacologic modulations targeting VEGF or its receptor may offer new therapeutic approaches. In this review, the authors integrate current knowledge of VEGF signaling and information on VEGF antagonists gleaned experimentally and place emphasis on the use of synthetic anti-VEGF hexapeptide to prevent VEGF interacting with its receptor.


2005 ◽  
Vol 23 (5) ◽  
pp. 1011-1027 ◽  
Author(s):  
Daniel J. Hicklin ◽  
Lee M. Ellis

New blood vessel formation (angiogenesis) is a fundamental event in the process of tumor growth and metastatic dissemination. Hence, the molecular basis of tumor angiogenesis has been of keen interest in the field of cancer research. The vascular endothelial growth factor (VEGF) pathway is well established as one of the key regulators of this process. The VEGF/VEGF-receptor axis is composed of multiple ligands and receptors with overlapping and distinct ligand-receptor binding specificities, cell-type expression, and function. Activation of the VEGF-receptor pathway triggers a network of signaling processes that promote endothelial cell growth, migration, and survival from pre-existing vasculature. In addition, VEGF mediates vessel permeability, and has been associated with malignant effusions. More recently, an important role for VEGF has emerged in mobilization of endothelial progenitor cells from the bone marrow to distant sites of neovascularization. The well-established role of VEGF in promoting tumor angiogenesis and the pathogenesis of human cancers has led to the rational design and development of agents that selectively target this pathway. Studies with various anti-VEGF/VEGF-receptor therapies have shown that these agents can potently inhibit angiogenesis and tumor growth in preclinical models. Recently, an anti-VEGF antibody (bevacizumab), when used in combination with chemotherapy, was shown to significantly improve survival and response rates in patients with metastatic colorectal cancer and thus, validate VEGF pathway inhibitors as an important new treatment modality in cancer therapy.


JHEP Reports ◽  
2021 ◽  
Vol 3 (3) ◽  
pp. 100251
Author(s):  
Valeria Mariotti ◽  
Romina Fiorotto ◽  
Massimiliano Cadamuro ◽  
Luca Fabris ◽  
Mario Strazzabosco

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 253
Author(s):  
Xi Guo ◽  
Hong Yi ◽  
Tin Chiu Li ◽  
Yu Wang ◽  
Huilin Wang ◽  
...  

Vascular endothelial growth factor (VEGF) is a well-known angiogenic factor that plays a critical role in various physiological and pathological processes. VEGF also contributes to the process of embryo implantation by enhancing embryo development, improving endometrial receptivity, and facilitating the interactions between the developing embryo and the endometrium. There is a correlation between the alteration of VEGF expression and reproductive failure, including recurrent implantation failure (RIF) and recurrent miscarriage (RM). In order to clarify the role of VEGF in embryo implantation, we reviewed recent literature concerning the expression and function of VEGF in the reproductive system around the time of embryo implantation and we provide a summary of the findings reported so far. We also explored the effects and the possible underlying mechanisms of action of VEGF in embryo implantation.


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