scholarly journals EphrinA1 Inhibits Vascular Endothelial Growth Factor-Induced Intracellular Signaling and Suppresses Retinal Neovascularization and Blood-Retinal Barrier Breakdown

2006 ◽  
Vol 168 (1) ◽  
pp. 331-339 ◽  
Author(s):  
Tomonari Ojima ◽  
Hitoshi Takagi ◽  
Kiyoshi Suzuma ◽  
Hideyasu Oh ◽  
Izumi Suzuma ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Intracellular Signaling ◽  
Retinal Neovascularization ◽  
Vascular Endothelial ◽  
Blood Retinal Barrier ◽  
Barrier Breakdown ◽  
Endothelial Growth Factor

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 ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Intraocular Pressure ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Blood Retinal Barrier ◽  
Intravitreous Injection ◽  
Anti Vegf ◽  
Endothelial Growth Factor ◽  
Brb Breakdown

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.

scholarly journals Evogliptin, a dipeptidyl peptidase-4 inhibitor, attenuates pathological retinal angiogenesis by suppressing vascular endothelial growth factor-induced Arf6 activation

2020 ◽  
Vol 52 (10) ◽  
pp. 1744-1753
Author(s):  
Songyi Seo ◽  
Mi-Kyung Kim ◽  
Ryul-I Kim ◽  
Yeongju Yeo ◽  
Koung Li Kim ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Dipeptidyl Peptidase ◽  
Inhibitory Effect ◽  
Retinal Neovascularization ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Dipeptidyl Peptidase 4 ◽  
Endothelial Growth Factor

Abstract Dipeptidyl peptidase-4 (DPP-4) inhibitors are used for the treatment of type 2 diabetes mellitus (DM). Recent studies have shown that beyond their effect in lowing glucose, DPP-4 inhibitors mitigate DM-related microvascular complications, such as diabetic retinopathy. However, the mechanism by which pathological retinal neovascularization, a major clinical manifestation of diabetic retinopathy, is inhibited is unclear. This study sought to examine the effects of evogliptin, a potent DPP-4 inhibitor, on pathological retinal neovascularization in mice and elucidate the mechanism by which evogliptin inhibits angiogenesis mediated by vascular endothelial growth factor (VEGF), a key factor in the vascular pathogenesis of proliferative diabetic retinopathy (PDR). In a murine model of PDR, an intravitreal injection of evogliptin significantly suppressed aberrant retinal neovascularization. In human endothelial cells, evogliptin reduced VEGF-induced angiogenesis. Western blot analysis showed that evogliptin inhibited the phosphorylation of signaling molecules associated with VEGF-induced cell adhesion and migration. Moreover, evogliptin substantially inhibited the VEGF-induced activation of adenosine 5′-diphosphate ribosylation factor 6 (Arf6), a small guanosine 5′-triphosphatase (GTPase) that regulates VEGF receptor 2 signal transduction. Direct activation of Arf6 using a chemical inhibitor of Arf-directed GTPase-activating protein completely abrogated the inhibitory effect of evogliptin on VEGF-induced activation of the angiogenic signaling pathway, which suggests that evogliptin suppresses VEGF-induced angiogenesis by blocking Arf6 activation. Our results provide insights into the molecular mechanism of the direct inhibitory effect of the DPP-4 inhibitor evogliptin on pathological retinal neovascularization. In addition to its glucose-lowering effect, the antiangiogenic effect of evogliptin could also render it beneficial for individuals with PDR.

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