scholarly journals Thy-1 Regulates VEGF-Mediated Choroidal Endothelial Cell Activation and Migration: Implications in Neovascular Age-Related Macular Degeneration

2016 ◽  
Vol 57 (13) ◽  
pp. 5525 ◽  
Author(s):  
Haibo Wang ◽  
Xiaokun Han ◽  
Eric Kunz ◽  
M. Elizabeth Hartnett
Keyword(s):  
Endothelial Cell ◽  
Macular Degeneration ◽  
Cell Activation ◽  
Age Related Macular Degeneration ◽  
Endothelial Cell Activation ◽  
Age Related ◽  
And Migration ◽  
Choroidal Endothelial Cell

scholarly journals Regulation of Rac1 Activation in Choroidal Endothelial Cells: Insights into Mechanisms in Age-Related Macular Degeneration

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2414
Author(s):  
Aniket Ramshekar ◽  
Haibo Wang ◽  
M. Elizabeth Hartnett
Keyword(s):  
Endothelial Cells ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Macular Degeneration ◽  
Neural Retina ◽  
Age Related Macular Degeneration ◽  
Endothelial Cell Migration ◽  
Iq Motif ◽  
Age Related ◽  
Choroidal Endothelial Cell

Age-related macular degeneration (AMD) is one of the leading causes of blindness worldwide. Vision loss from the neovascular form is associated with the invasion of choroidal endothelial cells into the neural retina to form vision-threatening macular neovascularization (MNV). Anti-angiogenic agents are the current standard of care but are effective in only ~50% of AMD cases. The molecular mechanisms involved in invasive MNV point to the importance of regulating signaling pathways that lead to pathologic biologic outcomes. In studies testing the effects of AMD-related stresses, activation of the Rho GTPase, Rac1, was found to be important for the choroidal endothelial cell invasion into the neural retina. However, current approaches to prevent Rac1 activation are inefficient and less effective. We summarize active Rac1-mediated mechanisms that regulate choroidal endothelial cell migration. Specifically, we discuss our work regarding the role of a multidomain protein, IQ motif containing GTPase activating protein 1 (IQGAP1), in sustaining pathologic Rac1 activation and a mechanism by which active Rap1, a Ras-like GTPase, may prevent active Rac1-mediated choroidal endothelial cell migration.

Serum anti-endothelial cell antibodies in patients with age-related macular degeneration treated with intravitreal bevacizumab

2016 ◽  
Vol 94 (7) ◽  
pp. e617-e623 ◽  
Author(s):  
Agnieszka Kubicka-Trząska ◽  
Joanna Wilańska ◽  
Bożena Romanowska-Dixon ◽  
Marek Sanak
Keyword(s):  
Endothelial Cell ◽  
Macular Degeneration ◽  
Intravitreal Bevacizumab ◽  
Age Related Macular Degeneration ◽  
Age Related

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.

scholarly journals SARAF and Orai1 Contribute to Endothelial Cell Activation and Angiogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Isabel Galeano-Otero ◽  
Raquel Del Toro ◽  
Abdel-Majid Khatib ◽  
Juan Antonio Rosado ◽  
Antonio Ordóñez-Fernández ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Activation ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Endothelial Cell Activation ◽  
Store Operated Calcium Entry ◽  
Multistep Process ◽  
Intracellular Ca ◽  
Angiogenesis Process ◽  
And Migration

Angiogenesis is a multistep process that controls endothelial cells (ECs) functioning to form new blood vessels from preexisting vascular beds. This process is tightly regulated by pro-angiogenic factors, such as vascular endothelial growth factor (VEGF), which promote signaling pathways involving the increase in the intracellular Ca2+ concentration ([Ca2+]i). Recent evidence suggests that store-operated calcium entry (SOCE) might play a role in angiogenesis. However, little is known regarding the role of SARAF, SOCE-associated regulatory factor, and Orai1, the pore-forming subunit of the store-operated calcium channel (SOCC), in angiogenesis. Here, we show that SOCE inhibition with GSK-7975A blocks aorta sprouting, as well as human umbilical vein endothelial cell (HUVEC) tube formation and migration. The intraperitoneal injection of GSK-7975A also delays the development of retinal vasculature assessed at postnatal day 6 in mice, since it reduces vessel length and the number of junctions, while it increases lacunarity. Moreover, we find that SARAF and Orai1 are involved in VEGF-mediated [Ca2+]i increase, and their knockdown using siRNA impairs HUVEC tube formation, proliferation, and migration. Finally, immunostaining and in situ proximity ligation assays indicate that SARAF likely interacts with Orai1 in HUVECs. Therefore, these findings show for the first time a functional interaction between SARAF and Orai1 in ECs and highlight their essential role in different steps of the angiogenesis process.

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