scholarly journals Ephrin-A5 Is Involved in Retinal Neovascularization in a Mouse Model of Oxygen-Induced Retinopathy

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Wei Du ◽  
Lvzhen Huang ◽  
Xin Tang ◽  
Jiarui Li ◽  
Xiaoxin Li
Keyword(s):  
Mouse Model ◽  
Vision Loss ◽  
Biological Significance ◽  
Retinal Neovascularization ◽  
Pathological Feature ◽  
Downstream Signaling ◽  
Oxygen Induced Retinopathy ◽  
Severe Vision Loss ◽  
Retinal Angiogenesis ◽  
The Impact

Retinal neovascularization (RNV) is an important pathological feature of vitreoretinopathy that can lead to severe vision loss. The purpose of this study was to identify the role of ephrin-A5 (Efna5) in RNV and to explore its mechanism. The expression pattern and biological significance of Efna5 were investigated in a mouse model of oxygen-induced retinopathy (OIR). The expression of Efna5 and downstream signaling pathway members was determined by RT-PCR, immunofluorescence, immunohistochemistry, and western blot analyses. shRNA was used to knockdown Efna5 in the retina of the OIR mouse model. Retinal flat mounts were performed to evaluate the impact of Efna5 silencing on the RNV process. We found that the Efna5 was greatly upregulated in the retina of OIR mice. Elevated Efna5 mainly colocalized with the retinal vessels and endothelial cells. We then showed that knockdown of Efna5 in OIR mouse retinas using lentivirus-mediated shRNA markedly decreased the expression of Efna5 and reduced the retinal neovascularization and avascular retina area. We further showed hypoxia stimulation dramatically increased both total and phosphorylation levels of ERK1/2 and the phosphorylation levels of Akt in OIR mice. More importantly, knockdown of Efna5 could inhibit the p-Akt and p-ERK signaling pathways. Our results suggested that Efna5 may regulate the RNV. This study suggests that Efna5 was significantly upregulated in the retina of OIR mice and closely involved in the pathological retinal angiogenesis.

MicroRNA-34a attenuates VEGF-mediated retinal angiogenesis via targeting Notch1

2019 ◽  
Vol 97 (4) ◽  
pp. 423-430 ◽  
Author(s):  
Shaoyang Shi ◽  
Yong Jin ◽  
Haishan Song ◽  
Xiaolong Chen
Keyword(s):  
Vision Loss ◽  
Tube Formation ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Matrix Metalloproteinase 2 ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Oxygen Induced Retinopathy ◽  
Gene Assay ◽  
Retinal Angiogenesis ◽  
Endothelial Growth Factor

Pathological angiogenesis in the retina is one of the main ocular diseases closely associated with vision loss. This work investigated the roles of microRNA-34a (miR-34a) and its potential target Notch1, in retinal angiogenesis. For this we used oxygen-induced retinopathy (OIR) rats and human retinal microvascular endothelial cells (HRMECs) stimulated with vascular endothelial growth factor (VEGF). We performed hematoxylin–eosin staining, Western blot for VEGF, and immunofluorescence staining for CD31 to verify the establishment of our OIR model. We observed down-regulation of miR-34a, and up-regulation of Notch1 and Hey1 in retinas from OIR rats. We found similar results with the VEGF-stimulated HRMECs. By performing MTT assay, cell scratch assay, tube formation assay, and by detecting the expression of matrix-metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitors of metalloproteinases-1 (TIMP-1), and TIMP-2, we found that transfection of miR-34a ameliorated VEGF-mediated angiogenesis of HRMECs. We further observed that siRNA-induced gene silencing of Notch1 prevented VEGF-induced angiogenesis via regulating cell proliferation, cell migration, and tube formation of HRMECs. Additionally, activation of Notch1 by transfection of Notch1 plasmid attenuated the inhibitory effects of miR-34a on tube formation, in the present of VEGF. Results from our dual-luciferase reporter gene assay suggested that miR-34a targets Notch1. In summary, our data demonstrate that miR-34a attenuates retinal angiogenesis via targeting Notch1.

The effect of sevoflurane on retinal angiogenesis in a mouse model of oxygen-induced retinopathy

2018 ◽  
Vol 32 (2) ◽  
pp. 204-210 ◽  
Author(s):  
Hee Young Kim ◽  
Seung-Hoon Baek ◽  
Seong Wan Baik ◽  
Sun Sik Bae ◽  
Jung Min Ha ◽  
...  
Keyword(s):  
Mouse Model ◽  
Oxygen Induced Retinopathy ◽  
Retinal Angiogenesis

Aquaporin 4 is required to induce retinal angiogenesis in a mouse model of oxygen-induced retinopathy

2014 ◽  
Vol 92 ◽  
pp. 0-0
Author(s):  
M DAL MONTE ◽  
GP NICCHIA ◽  
M CAMMALLERI ◽  
IA FRIGERI ◽  
I FORNACIARI ◽  
...  
Keyword(s):  
Mouse Model ◽  
Aquaporin 4 ◽  
Oxygen Induced Retinopathy ◽  
Retinal Angiogenesis

The Iron Chelator Deferiprone Improves the Phenotype in a Mouse Model of Tauopathy1

2020 ◽  
Vol 77 (2) ◽  
pp. 753-771 ◽  
Author(s):  
Shalini S. Rao ◽  
Stuart. D. Portbury ◽  
Larissa Lago ◽  
Ashley I. Bush ◽  
Paul A. Adlard
Keyword(s):  
Mouse Model ◽  
Inductively Coupled Plasma ◽  
Glycogen Synthase ◽  
Iron Chelator ◽  
Pathological Feature ◽  
Tau Pathology ◽  
Inductively Coupled ◽  
Y Maze ◽  
Metal Levels ◽  
The Impact

Background: Abnormally hyperphosphorylated tau is a defining pathological feature of tauopathies, such as Alzheimer’s disease (AD), and accumulating evidence suggests a role for iron in mediating tau pathology that may lead to cognitive decline in these conditions. The metal chelator deferiprone (DFP), which has a high affinity for iron, is currently in clinical trials for AD and Parkinson’s disease. However, the effect of DFP on tau pathology remains underexplored. Objective: We aimed to investigate the impact of chronic DFP treatment on tau pathology using a well-characterized mouse model of tauopathy (rTg(tauP301L)4510). Methods: Animals were treated daily with DFP (100 mg/kg) via oral gavage for 16 weeks. After 14 weeks, mice were tested in the Y-maze, open field, Morris water maze, and rotorod. At the end of the study, brain tissue was collected to examine metal levels (using inductively coupled plasma-mass spectrometry) and for western blot analysis of DFP on tau and iron associated pathways. Results: DFP significantly reduced anxiety-like behavior, and revealed a trend toward improved cognitive function. This was accompanied by a decrease in brain iron levels and sarkosyl-insoluble tau. Our data also showed downregulation of the tau kinases glycogen synthase kinase 3β and cyclin dependent kinase-5 in DFP treated mice and an increase in the methylation of the catalytic subunit of protein phosphatase 2A. Conclusion: These data support the hypothesis that suggests that iron plays a neurotoxic role in tauopathies and may be a potential therapeutic target for this class of disorders.

scholarly journals A Fairy Chemical Suppresses Retinal Angiogenesis as a HIF Inhibitor

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1405
Author(s):  
Deokho Lee ◽  
Yukihiro Miwa ◽  
Jing Wu ◽  
Chiho Shoda ◽  
Heonuk Jeong ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Inhibitory Effect ◽  
Retinal Neovascularization ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
Oxygen Induced Retinopathy ◽  
Hypoxic Conditions ◽  
Chronic Therapy ◽  
Retinal Angiogenesis ◽  
Endothelial Growth Factor

Neovascular retinal degeneration is a leading cause of blindness in advanced countries. Anti-vascular endothelial growth factor (VEGF) drugs have been used for neovascular retinal diseases; however, anti-VEGF drugs may cause the development of chorioretinal atrophy in chronic therapy as they affect the physiological amount of VEGF needed for retinal homeostasis. Hypoxia-inducible factor (HIF) is a transcription factor inducing VEGF expression under hypoxic and other stress conditions. Previously, we demonstrated that HIF was involved with pathological retinal angiogenesis in murine models of oxygen-induced retinopathy (OIR), and pharmacological HIF inhibition prevented retinal neovascularization by reducing an ectopic amount of VEGF. Along with this, we attempted to find novel effective HIF inhibitors. Compounds originally isolated from mushroom-forming fungi were screened for prospective HIF inhibitors utilizing cell lines of 3T3, ARPE-19 and 661W. A murine OIR model was used to examine the anti-angiogenic effects of the compounds. As a result, 2-azahypoxanthine (AHX) showed an inhibitory effect on HIF activation and suppressed Vegf mRNA upregulation under CoCl2-induced pseudo-hypoxic conditions. Oral administration of AHX significantly suppressed retinal neovascular tufts in the OIR model. These data suggest that AHX could be a promising anti-angiogenic agent in retinal neovascularization by inhibiting HIF activation.

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