scholarly journals Generating iPSC-Derived Choroidal Endothelial Cells to Study Age-Related Macular Degeneration

2015 ◽  
Vol 56 (13) ◽  
pp. 8258 ◽  
Author(s):  
Allison E. Songstad ◽  
Luke A. Wiley ◽  
Khahn Duong ◽  
Emily Kaalberg ◽  
Miles J. Flamme-Wiese ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Age Related

Different Populations of Circulating Endothelial Cells in Patients with Age-Related Macular Degeneration: A Novel Insight into Pathogenesis

2011 ◽  
Vol 52 (1) ◽  
pp. 93 ◽  
Author(s):  
Anna Machalinska ◽  
Krzysztof Safranow ◽  
Violetta Dziedziejko ◽  
Katarzyna Mozolewska-Piotrowska ◽  
Edyta Paczkowska ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Circulating Endothelial Cells ◽  
Age Related ◽  
Different Populations ◽  
Insight Into

scholarly journals Single-cell transcriptomics of the human retinal pigment epithelium and choroid in health and macular degeneration

2019 ◽  
Vol 116 (48) ◽  
pp. 24100-24107 ◽  
Author(s):  
Andrew P. Voigt ◽  
Kelly Mulfaul ◽  
Nathaniel K. Mullin ◽  
Miles J. Flamme-Wiese ◽  
Joseph C. Giacalone ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Single Cell ◽  
Rna Sequencing ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Single Cell Rna Sequencing

The human retinal pigment epithelium (RPE) and choroid are complex tissues that provide crucial support to the retina. Disease affecting either of these supportive tissues can lead to irreversible blindness in the setting of age-related macular degeneration. In this study, single-cell RNA sequencing was performed on macular and peripheral regions of RPE-choroid from 7 human donor eyes in 2 independent experiments. In the first experiment, total RPE/choroid preparations were evaluated and expression profiles specific to RPE and major choroidal cell populations were identified. As choroidal endothelial cells represent a minority of the total RPE/choroidal cell population but are strongly implicated in age-related macular degeneration (AMD) pathogenesis, a second single-cell RNA-sequencing experiment was performed using endothelial cells enriched by magnetic separation. In this second study, we identified gene expression signatures along the choroidal vascular tree, classifying the transcriptome of human choriocapillaris, arterial, and venous endothelial cells. We found that the choriocapillaris highly and specifically expresses the regulator of cell cycle gene (RGCC), a gene that responds to complement activation and induces apoptosis in endothelial cells. In addition, RGCC was the most up-regulated choriocapillaris gene in a donor diagnosed with AMD. These results provide a characterization of the human RPE and choriocapillaris transcriptome, offering potential insight into the mechanisms of choriocapillaris response to complement injury and choroidal vascular disease in age-related macular degeneration.

Hypocrellin B Encapsulated in Triphenyl Phosphonium-Modified Cationic Liposomes for Photodynamic Treatment of Exudative Age-Related Macular Degeneration

2019 ◽  
Vol 15 (12) ◽  
pp. 2305-2320
Author(s):  
Hongxia Chen ◽  
Hong Deng ◽  
Xianbiao Zou ◽  
Jingquan Zhao
Keyword(s):  
Endothelial Cells ◽  
Macular Degeneration ◽  
Vascular Endothelial Cells ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Age Related ◽  
Triphenyl Phosphonium ◽  
Hypocrellin B

Verteporfin photodynamic therapy (PDT) has been approved for the treatment of exudative age-related macular degeneration (AMD) for over a decade. However, its extensive application has been impeded by inevitably collateral tissue damage and immediate induction of angiogenesis, in addition to the need of multiple treatments. In order to develop prospective photosensitizers for clinical use, a triphenyl phosphonium-modified cationic liposomal hypocrellin B (TPP cationic LHB) for angiogenic targeting and endothelial internalization was constructed. With optimal PDT parameters, TPP cationic LHB can lead to death of choroid-retinal vascular endothelial cells while cause negligible damage to collateral retinal pigment epithelium cells. This is likely due to the mitochondria targeting and effective intracellular singlet oxygen generation of TPP cationic LHB in vascular endothelial cells. Additionally, in vivo chick chorioallantoic membrane assay indicated the elevated neovessel-targeting ability and photo-induced anti-angiogenic activity of TPP cationic LHB. Furthermore, TPP cationic LHB PDT is able to maintain neovessel occlusion for an extended period of time compared with verteporfin PDT, without inducing significant increased expression of some angiogenic factors, such as vascular endothelial growth factor and integrin αvβ3. This study describes a facile strategy that may be useful for developing new-generation photosensitizers to circumvent the limitations of PDT treatment of exudative AMD.

scholarly journals Comparative effects of Bevacizumab and Ranibizumab on endothelial cells. Implications in age‐related macular degeneration

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Raquel Costa ◽  
Ana Pirraco ◽  
Manuel Falcão ◽  
Ângela Carneiro ◽  
Ana Rocha ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Macular Degeneration ◽  
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.

Endothelial cells analysis after intravitreal ranibizumab (Lucentis) in age-related macular degeneration treatment: a pilot study

2010 ◽  
Vol 94 (2) ◽  
pp. 267-268 ◽  
Author(s):  
C. Perez-Rico ◽  
J. Benitez-Herreros ◽  
M. Castro-Rebollo ◽  
Y. Gomez-SanGil ◽  
F. Germain ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pilot Study ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Intravitreal Ranibizumab ◽  
Age Related

Circulating endothelial and progenitor cells in age-related macular degeneration

2019 ◽  
Vol 30 (5) ◽  
pp. 956-965
Author(s):  
Dario Pasquale Mucciolo ◽  
Rossella Marcucci ◽  
Andrea Sodi ◽  
Francesca Cesari ◽  
Vittoria Murro ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Macular Degeneration ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cell ◽  
Progenitor Cell ◽  
Age Related Macular Degeneration ◽  
Circulating Endothelial Cells ◽  
Control Group ◽  
Endothelial Progenitor ◽  
Age Related

Purpose: To evaluate circulating endothelial and circulating progenitor cells as biomarkers in age-related macular degeneration patients (both exudative and atrophic forms) in order to establish the possible clinical implication of their assessment. Methods: We have enrolled 44 age-related macular degeneration patients: 22 patients with a recently diagnosed exudative (neovascular) form (Group A) and 22 patients with an atrophic (dry) form (Group B). The control group consisted of 22 age and sex-matched healthy subjects (Group C). The number of circulating endothelial progenitor cells (CD34+/KDR+, CD133+/KDR+, and CD34+/KDR+/CD133+), circulating progenitor cells (CD34+, CD133+, and CD34+/CD133+), and circulating endothelial cells were determined in the peripheral venous blood samples by flow cytometry. Neovascular age-related macular degeneration patients were evaluated at baseline and 4 weeks after a loading phase of three consequent intravitreal injections of ranibizumab. Results: Comparing age-related macular degeneration patients with the control group, endothelial progenitor cell and circulating progenitor cell levels were not significantly different, while age-related macular degeneration patients showed significantly higher levels of circulating endothelial cells ( p = 0.001). Anti–vascular endothelial growth factor treatment with intravitreal ranibizumab was associated with a significant reduction of endothelial progenitor cell levels, with no significant influence on circulating progenitor cells and circulating endothelial cells. Conclusion: We reported higher levels of circulating endothelial cells in age-related macular degeneration patients in comparison with the control group, thereby supporting the hypothesis of an involvement of endothelial dysregulation in the age-related macular degeneration and a reduction of the endothelial progenitor cell level in neovascular age-related macular degeneration patients after three intravitreal injections of ranibizumab.

scholarly journals EGHB010, a Standardized Extract of Paeoniae Radix and Glycyrrhizae Radix, Inhibits VEGF-Induced Tube Formation In Vitro and Retinal Vascular Leakage and Choroidal Neovascularization In Vivo

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Eunsoo Jung ◽  
Wookwon Jung ◽  
Su-Bin Park ◽  
Chan-Sik Kim ◽  
Jin Sook Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Oral Administration ◽  
Macular Degeneration ◽  
Choroidal Neovascularization ◽  
Laser Photocoagulation ◽  
Tube Formation ◽  
Vascular Leakage ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Age Related

EGHB010 is a hot water extract of the rhizome mixture of Paeonia lactiflora Pallas and Glycyrrhiza uralensis Fisch. Choroidal neovascularization (CNV) and vascular leakage are the common pathophysiologies of age-related macular degeneration. In this study, we aimed to evaluate the effect of EGHB010 on retinal vascular leakage and laser-induced CNV in a rat model. Vascular endothelial growth factor- (VEGF-) induced tube formation was assayed in human retinal microvascular endothelial cells. Intravitreal VEGF-induced blood-retinal barrier breakdown was assayed in Sprague-Dawley rats. Experimental CNV was induced by laser photocoagulation in Brown Norway rats. EGHB010 (50 and 100 mg/kg/day) was administered orally for 10 days after laser photocoagulation. Choroidal flat mounts were prepared to measure the lesion size of CNV. Incubation of retinal vascular endothelial cells with EGHB010 (12.5 and 25 μg/mL) resulted in the inhibition of VEGF-induced tube formation in a dose-dependent manner. VEGF-mediated retinal vascular leakage was blocked by the oral administration of EGHB010. The CNV area was significantly lower in EGHB010-treated rats than in vehicle-treated rats. These results suggest that EGHB010 is a potent antiangiogenic agent. Thus, the oral administration of EGHB010 may have a beneficial effect in the treatment of vascular leakage and CNV in patients with age-related macular degeneration.

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