scholarly journals Relationship between Pericytes and Endothelial Cells in Retinal Neovascularization: A Histological and Immunofluorescent Study of Retinal Angiogenesis

2018 ◽  
Vol 32 (1) ◽  
pp. 70 ◽  
Author(s):  
Se Hyun Choi ◽  
Minhwan Chung ◽  
Sung Wook Park ◽  
Noo Li Jeon ◽  
Jeong Hun Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Retinal Neovascularization ◽  
Immunofluorescent Study ◽  
Retinal Angiogenesis

scholarly journals Inhibiting the NLRP3 inflammasome with MCC950 ameliorates retinal neovascularization and leakage by reversing the IL-1β/IL-18 activation pattern in an oxygen-induced ischemic retinopathy mouse model

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Ailing Sui ◽  
Xiuping Chen ◽  
Jikui Shen ◽  
Anna M. Demetriades ◽  
Yiyun Yao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Nlrp3 Inflammasome ◽  
Retinal Neovascularization ◽  
Platelet Derived Growth Factor ◽  
Vegf Receptor ◽  
Activation Pattern ◽  
Ischemic Retinopathy

Abstract Activation of the nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor 3 (NLRP3) inflammasome plays an important role in ocular neovascularization. In our study, we found that the expression and activation levels of NLRP3 inflammasome components, including NLRP3, an apoptosis-associated speck-like protein (ASC) containing caspase activation and recruitment domain (CARD) and caspase-1 (CAS1), were significantly upregulated. In addition, we found interleukin (IL)-1β activity increased while IL-18 activity decreased in the retinas of oxygen-induced ischemic retinopathy (OIR) mice. MCC950, an inhibitor of NLRP3, reversed the IL-1β/IL-18 activation pattern, inhibited the formation of retinal neovascularization (RNV), decreased the number of acellular capillaries and reduced leakage of retinal vessels. Moreover, MCC950 could regulate the expression of endothelial cell- and pericyte function-associated molecules, such as vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)1, VEGFR2, matrix metalloproteinase (MMP)2, MMP9, tissue inhibitor of metalloproteinases (TIMP)1, TIMP2, platelet-derived growth factor receptor-β (PDGFR-β), platelet-derived growth factor-B (PDGF-B), and angiopoietin2 (Ang2). In vitro, recombinant human (r)IL-18 and rIL-1β regulated the expression of endothelial cell- and pericyte function-associated molecules and the proliferation and migration of endothelial cells and pericytes. We therefore determined that inhibiting the NLRP3 inflammasome with MCC950 can regulate the function of endothelial cells and pericytes by reversing the IL-1β/IL-18 activation pattern to ameliorate RNV and leakage; thereby opening new avenues to treat RNV-associated ocular diseases.

scholarly journals THE PATHOGENIC ROLE OF FIBRIN DEPOSITION IN THE GLOMERULAR LESIONS OF TOXEMIA OF PREGNANCY

1963 ◽  
Vol 118 (3) ◽  
pp. 467-478 ◽  
Author(s):  
Pierre Vassalli ◽  
Robert H. Morris ◽  
Robert T. McCluskey
Keyword(s):  
Endothelial Cells ◽  
Basement Membrane ◽  
Gamma Globulin ◽  
Fibrin Deposition ◽  
Pathogenic Role ◽  
Immunofluorescent Study ◽  
Renal Biopsies ◽  
Glomerular Lesions ◽  
Glomerular Damage

An immunofluorescent study of renal biopsies from patients with toxemia of pregnancy has been performed. It was found that the glomeruli consistently showed bright staining for fibrin within endothelial cells, as well as occasional deposits along the basement membrane. Gamma globulin was only occasionally demonstrable, generally in the form of irregular deposits along the basement membrane. ß1C was absent and albumin was not seen in glomeruli, except sometimes in the form of droplets within epithelial cells. In biopsies from pregnant patients without toxemia only equivocal staining for fibrin was seen. On the basis of these observations and other evidence discussed, it is proposed that the accumulation of fibrin in glomeruli reflects a prolonged state of intravascular clotting in toxemia and that the arrest in glomeruli of some form of circulating fibrin constitutes the basic pathogenic mechanism of the glomerular damage in this disease.

scholarly journals Correction: Co-culture of Retinal and Endothelial Cells Results in the Modulation of Genes Critical to Retinal Neovascularization

Vascular Cell ◽  
2012 ◽  
Vol 4 (1) ◽  
pp. 6 ◽  
Author(s):  
Ravindra Kumar ◽  
Sandra Harris-Hooker ◽  
Ritesh Kumar ◽  
Gary Sanford
Keyword(s):  
Endothelial Cells ◽  
Retinal Neovascularization

scholarly journals Heme relieves the inhibition of proliferation, migration and angiogenesis of HMEC-1 under hyperoxia by inhibiting BACH1

2020 ◽  
Author(s):  
Lan Jian ◽  
Yang Mei ◽  
Yuan Rongdi
Keyword(s):  
Endothelial Cells ◽  
Phase I ◽  
Scratch Test ◽  
Cell Counting ◽  
Endothelial Cell Proliferation ◽  
Microvascular Endothelial Cells ◽  
Inhibition Of Proliferation ◽  
Retinal Angiogenesis ◽  
Microvascular Endothelial ◽  
Endothelial Growth Factor

Abstract Background The relatively hyperoxia inhibited vascular endothelial growth factor (VEGF) in retina is the main cause of angiogenesis retardation in phase I retinopathy of prematurity (ROP). Human retinal angiogenesis is related to the proliferation, migration and angiogenesis of microvascular endothelial cells. Previous studies have confirmed that BTB and CNC homology l (BACH1) can inhibit VEGF and angiogenesis, while heme can specifically degrade BACH1. However, the effect of heme on endothelial cells and ROP remains unknown. Methods In this report, we established a model of human microvascular endothelial cells (HMEC-1) induced by 40% hyperoxia to simulate the relatively hyperoxia of phase I ROP. Meanwhile, heme was added to investigate the effects on the growth and viability of HMEC-1. Cell counting kit 8 (CCK8) and 5-ethynyl-2′-deox-yuridine (EDU) methods were used to detect the proliferation ability. Cell scratch test and matrigel matrix glue were used to detect the migration or angiogenesis ability. Western blot and immunofluorescence methods were used to detect the relative protein expression of BACH1 and VEGF. Results The proliferation, migration and angiogenesis of HMEC-1 were inhibited under hyperoxia. Moderate heme can promote endothelial cell proliferation, while excessive can inhibit, 20 µM heme could inhibit the expression of BACH1, promote the expression of VEGF, and relieve the inhibition of proliferation, migration and angiogenesis induced by hyperoxia in HMEC-1. Conclusions 20 µM heme can relieve the inhibitory effects induced by hyperoxia, via the mechanism of promoting VEGF by inhibiting BACH1 in HMEC-1, and maybe a potential medicine for retinal angiogenesis retardation induced by relatively hyperoxia in phase I ROP.

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.

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.

scholarly journals Hyaloid Vasculature as a Major Source of STAT3 + (Signal Transducer and Activator of Transcription 3) Myeloid Cells for Pathogenic Retinal Neovascularization in Oxygen-Induced Retinopathy

2020 ◽  
Vol 40 (12) ◽  
Author(s):  
Jose R. Hombrebueno ◽  
Aisling Lynch ◽  
Eimear M. Byrne ◽  
Gideon Obasanmi ◽  
Adrien Kissenpfennig ◽  
...  
Keyword(s):  
Myeloid Cells ◽  
Retinal Neovascularization ◽  
Cytokine Signaling ◽  
Strongly Correlated ◽  
Signal Transducer ◽  
Oxygen Induced Retinopathy ◽  
Retinal Angiogenesis ◽  
Ischemic Retina ◽  
Transcription 3 ◽  
Hyaloid Vasculature

Objective: Myeloid cells are critically involved in inflammation-induced angiogenesis, although their pathogenic role in the ischemic retina remains controversial. We hypothesize that myeloid cells contribute to pathogenic neovascularization in retinopathy of prematurity through STAT3 (signal transducer and activator of transcription 3) activation. Approach and Results: Using the mouse model of oxygen-induced retinopathy, we show that myeloid cells (CD45 + IsolectinB4 [IB4] + ) and particularly M2-type macrophages (CD45 + Arg1 + ), comprise a major source of STAT3 activation (pSTAT3) in the immature ischemic retina. Most of the pSTAT3-expressing myeloid cells concentrated at the hyaloid vasculature and their numbers were strongly correlated with the severity of pathogenic neovascular tuft formation. Pharmacological inhibition of STAT3 reduced the load of IB4 + cells in the hyaloid vasculature and significantly reduced the formation of pathogenic neovascular tufts during oxygen-induced retinopathy, leading to improved long-term visual outcomes (ie, increased retinal thickness and scotopic b-wave electroretinogram responses). Genetic deletion of SOCS3 (suppressor of cytokine signaling 3), an endogenous inhibitor of STAT3, in myeloid cells, enhanced pathological and physiological neovascularization in oxygen-induced retinopathy, indicating that myeloid-STAT3 signaling is crucial for retinal angiogenesis. Conclusions: Circulating myeloid cells may migrate to the immature ischemic retina through the hyaloid vasculature and contribute to retinal neovascularization via activation of STAT3. Understanding how STAT3 modulates myeloid cells for vascular repair/pathology may provide novel therapeutic options in pathogenic angiogenesis.

scholarly journals Overexpression of Twist1 in vascular endothelial cells promotes pathological retinal angiogenesis in mice

2021 ◽  
Vol 43 (0) ◽  
pp. 1-11
Author(s):  
Lin Zhang ◽  
◽  
◽  
Shan-Shan Zhang ◽  
Kai-Fang Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Retinal Angiogenesis
Sign in / Sign up

Export Citation Format

Share Document