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Sample records for progenitor cell-induced neovascularization

  1. Cathepsin L is required for endothelial progenitor cell-induced neovascularization

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    Urbich, Carmen; Heeschen, Christopher; Aicher, Alexandra; Sasaki, Ken-ichiro; Bruhl, Thomas; Hofmann, Wolf K.; Peters, Christoph; Reinheckel, Thomas; Pennacchio, Len A.; Abolmaali, Nasreddin D.; Chavakis, Emmanouil; Zeiher, Andreas M.; Dimmeler, Stefanie

    2004-01-15

    Infusion of endothelial progenitor cells (EPCs), but not of mature endothelial cells (ECs), promotes neovascularization after ischemia. We performed a gene expression profiling of EPCs and ECs to identify genes, which might be important for the neovascularization capacity of EPCs. Intriguingly, the protease cathepsin L (CathL) was highly expressed in EPCs as opposed to ECs and is essential for matrix degradation and invasion by EPCs in vitro. CathL deficient mice showed impaired functional recovery after hind limb ischemia supporting the concept for an important role of CathL in postnatal neovascularization. Infused CathL deficient progenitor cells failed to home to sites of ischemia and to augment neovascularization. In contrast, over expression of CathL in mature ECs significantly enhanced their invasive activity and induced their neovascularization capacity in vivo. Taken together, CathL plays a crucial role for the integration of circulating EPCs into the ischemic tissue and is required for neovascularization mediated by EPCs.

  2. Modeling Stem/Progenitor Cell-Induced Neovascularization and Oxygenation Around Solid Implants

    KAUST Repository

    Jain, Harsh Vardhan

    2012-07-01

    Tissue engineering constructs and other solid implants with biomedical applications, such as drug delivery devices or bioartificial organs, need oxygen (O(2)) to function properly. To understand better the vascular integration of such devices, we recently developed a novel model sensor containing O(2)-sensitive crystals, consisting of a polymeric capsule limited by a nanoporous filter. The sensor was implanted in mice with hydrogel alone (control) or hydrogel embedded with mouse CD117/c-kit+ bone marrow progenitor cells in order to stimulate peri-implant neovascularization. The sensor provided local partial O(2) pressure (pO(2)) using noninvasive electron paramagnetic resonance signal measurements. A consistently higher level of peri-implant oxygenation was observed in the cell-treatment case than in the control over a 10-week period. To provide a mechanistic explanation of these experimental observations, we present in this article a mathematical model, formulated as a system of coupled partial differential equations, that simulates peri-implant vascularization. In the control case, vascularization is considered to be the result of a foreign body reaction, while in the cell-treatment case, adipogenesis in response to paracrine stimuli produced by the stem cells is assumed to induce neovascularization. The model is validated by fitting numerical predictions of local pO(2) to measurements from the implanted sensor. The model is then used to investigate further the potential for using stem cell treatment to enhance the vascular integration of biomedical implants. We thus demonstrate how mathematical modeling combined with experimentation can be used to infer how vasculature develops around biomedical implants in control and stem cell-treated cases.

  3. Modeling Stem/Progenitor Cell-Induced Neovascularization and Oxygenation Around Solid Implants

    KAUST Repository

    Jain, Harsh Vardhan; Moldovan, Nicanor I.; Byrne, Helen M.

    2012-01-01

    Tissue engineering constructs and other solid implants with biomedical applications, such as drug delivery devices or bioartificial organs, need oxygen (O(2)) to function properly. To understand better the vascular integration of such devices, we recently developed a novel model sensor containing O(2)-sensitive crystals, consisting of a polymeric capsule limited by a nanoporous filter. The sensor was implanted in mice with hydrogel alone (control) or hydrogel embedded with mouse CD117/c-kit+ bone marrow progenitor cells in order to stimulate peri-implant neovascularization. The sensor provided local partial O(2) pressure (pO(2)) using noninvasive electron paramagnetic resonance signal measurements. A consistently higher level of peri-implant oxygenation was observed in the cell-treatment case than in the control over a 10-week period. To provide a mechanistic explanation of these experimental observations, we present in this article a mathematical model, formulated as a system of coupled partial differential equations, that simulates peri-implant vascularization. In the control case, vascularization is considered to be the result of a foreign body reaction, while in the cell-treatment case, adipogenesis in response to paracrine stimuli produced by the stem cells is assumed to induce neovascularization. The model is validated by fitting numerical predictions of local pO(2) to measurements from the implanted sensor. The model is then used to investigate further the potential for using stem cell treatment to enhance the vascular integration of biomedical implants. We thus demonstrate how mathematical modeling combined with experimentation can be used to infer how vasculature develops around biomedical implants in control and stem cell-treated cases.

  4. Modeling Stem/Progenitor Cell-Induced Neovascularization and Oxygenation Around Solid Implants

    Science.gov (United States)

    Moldovan, Nicanor I.; Byrne, Helen M.

    2012-01-01

    Tissue engineering constructs and other solid implants with biomedical applications, such as drug delivery devices or bioartificial organs, need oxygen (O2) to function properly. To understand better the vascular integration of such devices, we recently developed a novel model sensor containing O2-sensitive crystals, consisting of a polymeric capsule limited by a nanoporous filter. The sensor was implanted in mice with hydrogel alone (control) or hydrogel embedded with mouse CD117/c-kit+ bone marrow progenitor cells in order to stimulate peri-implant neovascularization. The sensor provided local partial O2 pressure (pO2) using noninvasive electron paramagnetic resonance signal measurements. A consistently higher level of peri-implant oxygenation was observed in the cell-treatment case than in the control over a 10-week period. To provide a mechanistic explanation of these experimental observations, we present in this article a mathematical model, formulated as a system of coupled partial differential equations, that simulates peri-implant vascularization. In the control case, vascularization is considered to be the result of a foreign body reaction, while in the cell-treatment case, adipogenesis in response to paracrine stimuli produced by the stem cells is assumed to induce neovascularization. The model is validated by fitting numerical predictions of local pO2 to measurements from the implanted sensor. The model is then used to investigate further the potential for using stem cell treatment to enhance the vascular integration of biomedical implants. We thus demonstrate how mathematical modeling combined with experimentation can be used to infer how vasculature develops around biomedical implants in control and stem cell-treated cases. PMID:22224628

  5. Endothelial progenitor cell-based neovascularization : implications for therapy

    NARCIS (Netherlands)

    Krenning, Guido; van Luyn, Marja J. A.; Harmsen, Martin C.

    Ischemic cardiovascular events are a major cause of death globally. Endothelial progenitor cell (EPC)-based approaches can result in improvement of vascular perfusion and might offer clinical benefit. However, although functional improvement is observed, the lack of long-term engraftment of EPCs

  6. Estradiol-induced, endothelial progenitor cell-mediated neovascularization in male mice with hind-limb ischemia

    NARCIS (Netherlands)

    Ruifrok, Willem-Peter T.; de Boer, Rudolf A.; Iwakura, Atsushi; Silver, Marcy; Kusano, Kengo; Tio, Rene A.; Losordo, Douglas W.

    We investigated whether administration of estradiol to male mice augments mobilization of bone marrow-derived endothelial progenitor cells (EPC) and incorporation into foci of neovascularization after hind-limb ischemia, thereby contributing to blood flow restoration. Mice were randomized and

  7. Aromatic Hydrocarbon Receptor Suppresses Prostate Cancer Bone Metastasis Cells-Induced Vasculogenesis of Endothelial Progenitor Cells under Hypoxia

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    Shuai Huang

    2016-07-01

    Full Text Available Background/Aims: Hypoxia leads to the development of neovascularization in solid tumor by regulating VEGF expression. Aromatic hydrocarbon receptor (AHR, a receptor for dioxin-like compounds, functions as a transcription factor through dimerization with hypoxia-inducible factors 1β (HIF-1β and inhibits the secretion of vascular endothelial growth factor (VEGF. The purpose of this study was to explore whether AHR can suppress hypoxia-induced VEGF production in prostate bone metastasis cells and repress neovascularization in endothelial progenitor cells (EPCs, and, if so, through what mechanisms. Methods: PC-3 or LNCaP cells induced angiogenesis was detected by Matrigel-based tube formation assay, mRNA expression levels was measured by qRT-PCR, VEGF secretion level was determined by ELISA assay, respectively. Results: AHR activation inhibits hypoxia-induced adhesiveness and vasculogenesis of EPCs induced by PC-3 or LNCaP cells under hypoxia. Moreover, AHR activation suppressed hypoxia-induced VEGF production in PC-3 and LNCaP cells (48 ± 14% in PC-3, p = 0.000; 41 ± 14% in LNCaP, p = 0.000 by attenuating HIF-1α and HIF-1β level that in turn diminished the angiogenic ability of EPCs in vitro. Furthermore, we found the mRNA level of hypoxia-inducible factors 1α (HIF-1α (1.54 ± 0.13 fold in PC-3, p = 0.002, 1.62 ± 0.12 fold in LNCaP, p = 0.001 and HIF-1β (1.67 ± 0.23 fold in PC-3, p = 0.007; 1.75 ± 0.26 fold in LNCaP, p=0.008 were upregulated in prostate cancer bone metastasis PC-3 and LNCaP cell lines in response to hypoxia, and revealed that the regulation of VEGF by HIF-1α and HIF-1β was possibly mediated by the activation of phosphatidylinositol 3-kinase pathway. Conclusion: By providing a mechanistic insight into the modulation of neovascularization by AHR ligand, we suggest that AHR ligand has a strong potential of being a new therapeutic agent with applications in the field of bone metastatic prostate cancer.

  8. Amlodipine Ameliorates Ischemia-Induced Neovascularization in Diabetic Rats through Endothelial Progenitor Cell Mobilization

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    Jiayin Sun

    2016-01-01

    Full Text Available Objectives. We investigated whether amlodipine could improve angiogenic responses in a diabetic rat model of acute myocardial infarction (AMI through improving bone marrow endothelial progenitor cell (EPC mobilization, in the same way as angiotensin converting enzyme inhibitors. Methods. After induction of AMI by coronary artery ligation, diabetic rats were randomly assigned to receive perindopril (2 mgkg−1 day−1, amlodipine (2.5 mgkg−1 day−1, or vehicle by gavage (n=20 per group. Circulating EPC counts before ligation and on days 1, 3, 5, 7, 14, and 28 after AMI were measured in each group. Microvessel density, cardiac function, and cardiac remodeling were assessed 4 weeks after treatment. The signaling pathway related to EPC mobilization was also measured. Results. Circulating EPC count in amlodipine- and perindopril-treated rats peaked at day 7, to an obvious higher level than the control group peak which was reached earlier (at day 5. Rats treated with amlodipine showed improved postischemia neovascularization and cardiac function, together with reduced cardiac remodeling, decreased interstitial fibrosis, and cardiomyocyte apoptosis. Amlodipine treatment also increased cardiac SDF-1/CXCR4 expression and gave rise to activation of VEGF/Akt/eNOS signaling in bone marrow. Conclusions. Amlodipine promotes neovascularization by improving EPC mobilization from bone marrow in diabetic rats after AMI, and activation of VEGF/Akt/eNOS signaling may in part contribute to this.

  9. Zoledronate inhibits ischemia-induced neovascularization by impairing the mobilization and function of endothelial progenitor cells.

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    Shih-Hung Tsai

    Full Text Available BACKGROUND: Bisphosphonates are a class of pharmacologic compounds that are commonly used to treat postmenopausal osteoporosis and malignant osteolytic processes. Studies have shown that bone marrow-derived endothelial progenitor cells (EPCs play a significant role in postnatal neovascularization. Whether the nitrogen-containing bisphosphonate zoledronate inhibits ischemia-induced neovascularization by modulating EPC functions remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Unilateral hindlimb ischemia was surgically induced in wild-type mice after 2 weeks of treatment with vehicle or zoledronate (low-dose: 30 μg/kg; high-dose: 100 μg/kg. Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio was significantly lower in wild-type mice treated with low-dose zoledronate and in mice treated with high-dose zoledronate than in controls 4 weeks after ischemic surgery (control vs. low-dose vs. high-dose: 87±7% vs. *61±18% vs. **49±17%, *p<0.01, **p<0.005 compared to control. Capillary densities were also significantly lower in mice treated with low-dose zoledronate and in mice treated with high-dose zoledronate than in control mice. Flow cytometry analysis showed impaired mobilization of EPC-like cells (Sca-1(+/Flk-1(+ after surgical induction of ischemia in mice treated with zoledronate but normal levels of mobilization in mice treated with vehicle. In addition, ischemic tissue from mice that received zoledronate treatment exhibited significantly lower levels of the active form of MMP-9, lower levels of VEGF, and lower levels of phosphorylated eNOS and phosphorylated Akt than ischemic tissue from mice that received vehicle. Results of the in vitro studies showed that incubation with zoledronate inhibited the viability, migration, and tube-forming capacities of EPC. CONCLUSIONS/SIGNIFICANCE: Zoledronate inhibited ischemia-induced neovascularization by impairing EPC mobilization and angiogenic functions

  10. A PEDF-Derived Peptide Inhibits Retinal Neovascularization and Blocks Mobilization of Bone Marrow-Derived Endothelial Progenitor Cells

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    Richard Longeras

    2012-01-01

    Full Text Available Proliferative diabetic retinopathy is characterized by pathological retinal neovascularization, mediated by both angiogenesis (involving mature endothelial cells and vasculogenesis (involving bone marrow-derived circulating endothelial progenitor cells (EPCs. Pigment epithelium-derived factor (PEDF contains an N-terminal 34-amino acid peptide (PEDF-34 that has antiangiogenic properties. Herein, we present a novel finding that PEDF-34 also possesses antivasculogenic activity. In the oxygen-induced retinopathy (OIR model using transgenic mice that have Tie2 promoter-driven GFP expression, we quantified Tie2GFP+ cells in bone marrow and peripheral blood by fluorescence-activated cell sorting (FACS. OIR significantly increased the number of circulating Tie2-GFP+ at P16, correlating with the peak progression of neovascularization. Daily intraperitoneal injections of PEDF-34 into OIR mice decreased the number of Tie2-GFP+ cells in the circulation at P16 by 65% but did not affect the number of Tie2-GFP+ cells in the bone marrow. These studies suggest that PEDF-34 attenuates EPC mobilization from the bone marrow into the blood circulation during retinal neovascularization.

  11. Enhanced generation of retinal progenitor cells from human retinal pigment epithelial cells induced by amniotic fluid

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    Sanie-Jahromi Fatemeh

    2012-04-01

    Full Text Available Abstract Background Retinal progenitor cells are a convenient source of cell replacement therapy in retinal degenerative disorders. The purpose of this study was to evaluate the expression patterns of the homeobox genes PAX6 and CHX10 (retinal progenitor markers during treatment of human retinal pigment epithelium (RPE cells with amniotic fluid (AF, RPE cells harvested from neonatal cadaver globes were cultured in a mixture of DMEM and Ham's F12 supplemented with 10% FBS. At different passages, cells were trypsinized and co-cultured with 30% AF obtained from normal fetuses of 1416 weeks gestational age. Results Compared to FBS-treated controls, AF-treated cultures exhibited special morphological changes in culture, including appearance of spheroid colonies, improved initial cell adhesion and ordered cell alignment. Cell proliferation assays indicated a remarkable increase in the proliferation rate of RPE cells cultivated in 30% AF-supplemented medium, compared with those grown in the absence of AF. Immunocytochemical analyses exhibited nuclear localization of retinal progenitor markers at a ratio of 33% and 27% for CHX10 and PAX6, respectively. This indicated a 3-fold increase in retinal progenitor markers in AF-treated cultures compared to FBS-treated controls. Real-time PCR data of retinal progenitor genes (PAX6, CHX10 and VSX-1 confirmed these results and demonstrated AF's capacity for promoting retinal progenitor cell generation. Conclusion Taken together, the results suggest that AF significantly promotes the rate of retinal progenitor cell generation, indicating that AF can be used as an enriched supplement for serum-free media used for the in vitro propagation of human progenitor cells.

  12. Enhanced generation of retinal progenitor cells from human retinal pigment epithelial cells induced by amniotic fluid.

    Science.gov (United States)

    Sanie-Jahromi, Fatemeh; Ahmadieh, Hamid; Soheili, Zahra-Soheila; Davari, Maliheh; Ghaderi, Shima; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Deezagi, Abdolkhalegh; Pakravesh, Jalil; Bagheri, Abouzar

    2012-04-10

    Retinal progenitor cells are a convenient source of cell replacement therapy in retinal degenerative disorders. The purpose of this study was to evaluate the expression patterns of the homeobox genes PAX6 and CHX10 (retinal progenitor markers) during treatment of human retinal pigment epithelium (RPE) cells with amniotic fluid (AF), RPE cells harvested from neonatal cadaver globes were cultured in a mixture of DMEM and Ham's F12 supplemented with 10% FBS. At different passages, cells were trypsinized and co-cultured with 30% AF obtained from normal fetuses of 1416 weeks gestational age. Compared to FBS-treated controls, AF-treated cultures exhibited special morphological changes in culture, including appearance of spheroid colonies, improved initial cell adhesion and ordered cell alignment. Cell proliferation assays indicated a remarkable increase in the proliferation rate of RPE cells cultivated in 30% AF-supplemented medium, compared with those grown in the absence of AF. Immunocytochemical analyses exhibited nuclear localization of retinal progenitor markers at a ratio of 33% and 27% for CHX10 and PAX6, respectively. This indicated a 3-fold increase in retinal progenitor markers in AF-treated cultures compared to FBS-treated controls. Real-time PCR data of retinal progenitor genes (PAX6, CHX10 and VSX-1) confirmed these results and demonstrated AF's capacity for promoting retinal progenitor cell generation. Taken together, the results suggest that AF significantly promotes the rate of retinal progenitor cell generation, indicating that AF can be used as an enriched supplement for serum-free media used for the in vitro propagation of human progenitor cells.

  13. CD34/CD133 enriched bone marrow progenitor cells promote neovascularization of tissue engineered constructs in vivo

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    Marietta Herrmann

    2014-11-01

    We demonstrate that this population of cells, isolated in a clinically relevant manner and cultured with autologous growth factors readily promoted neovascularization in tissue engineered constructs in vivo enabling a potential translation into the clinic.

  14. Complications impaired endothelial progenitor cell function in Type 2 diabetic patients with or without critical leg ischaemia: implication for impaired neovascularization in diabetes.

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    Chen, M-C; Sheu, J-J; Wang, P-W; Chen, C-Y; Kuo, M-C; Hsieh, C-J; Chen, J-F; Chang, H-W

    2009-02-01

    This study tested the hypothesis that migratory function of endothelial progenitor cells (EPCs) is impaired in Type 2 diabetic patients with or without critical leg ischaemia. Seventy-four patients were classified into four groups: Type 2 diabetic (n = 21) and non-diabetic patients (n = 10) with critical leg ischaemia and Type 2 diabetic patients without lower extremity vascular disease (n = 30) and healthy subjects (n = 13). The number and functional activity of circulating and cultured EPCs were determined. The migratory function of cultured EPCs was significantly impaired in diabetic patients without (median, 48, interquartile range, 46, 49 count/view/well) and with (median, 51, interquartile range, 46, 60 count/view/well) critical leg ischaemia and non-diabetic patients with critical leg ischaemia (median, 49, interquartile range, 47, 55 count/view/well) compared with healthy subjects (median, 63, interquartile range, 57, 65 count/view/well) (P interquartile range, 1600, 6600/10(6) cytometric events) than Type 2 diabetic patients with critical leg ischaemia (median, 5300, interquartile range, 2400, 11,100/10(6) cytometric events), non-diabetic patients with critical leg ischaemia (median, 5550, interquartile range, 2000, 32,100/10(6) cytometric events) and healthy subjects (median, 5400, interquartile range, 2700, 8700/10(6) cytometric events) (P = 0.413). The migratory function of EPCs is impaired in patients with Type 2 diabetes, even in those without critical leg ischaemia. These findings present an important new insight into the pathogenesis of impaired neovascularization and critical limb ischaemia in diabetic patients and provide avenues of future clinical study.

  15. GroEL1, a heat shock protein 60 of Chlamydia pneumoniae, impairs neovascularization by decreasing endothelial progenitor cell function.

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    Yi-Wen Lin

    Full Text Available The number and function of endothelial progenitor cells (EPCs are sensitive to hyperglycemia, hypertension, and smoking in humans, which are also associated with the development of atherosclerosis. GroEL1 from Chlamydia pneumoniae has been found in atherosclerotic lesions and is related to atherosclerotic pathogenesis. However, the actual effects of GroEL1 on EPC function are unclear. In this study, we investigate the EPC function in GroEL1-administered hind limb-ischemic C57BL/B6 and C57BL/10ScNJ (a toll-like receptor 4 (TLR4 mutation mice and human EPCs. In mice, laser Doppler imaging, flow cytometry, and immunohistochemistry were used to evaluate the degree of neo-vasculogenesis, circulating level of EPCs, and expression of CD34, vWF, and endothelial nitric oxide synthase (eNOS in vessels. Blood flow in the ischemic limb was significantly impaired in C57BL/B6 but not C57BL/10ScNJ mice treated with GroEL1. Circulating EPCs were also decreased after GroEL1 administration in C57BL/B6 mice. Additionally, GroEL1 inhibited the expression of CD34 and eNOS in C57BL/B6 ischemic muscle. In vitro, GroEL1 impaired the capacity of differentiation, mobilization, tube formation, and migration of EPCs. GroEL1 increased senescence, which was mediated by caspases, p38 MAPK, and ERK1/2 signaling in EPCs. Furthermore, GroEL1 decreased integrin and E-selectin expression and induced inflammatory responses in EPCs. In conclusion, these findings suggest that TLR4 and impaired NO-related mechanisms could contribute to the reduced number and functional activity of EPCs in the presence of GroEL1 from C. pneumoniae.

  16. Direct Cell-Cell Contact between Mesenchymal Stem Cells and Endothelial Progenitor Cells Induces a Pericyte-Like Phenotype In Vitro

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    Markus Loibl

    2014-01-01

    Full Text Available Tissue engineering techniques for the regeneration of large bone defects require sufficient vascularisation of the applied constructs to ensure a sufficient supply of oxygen and nutrients. In our previous work, prevascularised 3D scaffolds have been successfully established by coculture of bone marrow derived stem cells (MSCs and endothelial progenitor cells (EPCs. We identified stabilising pericytes (PCs as part of newly formed capillary-like structures. In the present study, we report preliminary data on the interactions between MSCs and EPCs, leading to the differentiation of pericyte-like cells. MSCs and EPCs were seeded in transwell cultures, direct cocultures, and single cultures. Cells were cultured for 10 days in IMDM 10% FCS or IMDM 5% FCS 5% platelet lysate medium. Gene expression of PC markers, CD146, NG2, αSMA, and PDGFR-β, was analysed using RT-PCR at days 0, 3, 7, and 10. The upregulation of CD146, NG2, and αSMA in MSCs in direct coculture with EPCs advocates the MSCs’ differentiation towards a pericyte-like phenotype in vitro. These results suggest that pericyte-like cells derive from MSCs and that cell-cell contact with EPCs is an important factor for this differentiation process. These findings emphasise the concept of coculture strategies to promote angiogenesis for cell-based tissue engineered bone grafts.

  17. [OCT and neovascular glaucoma].

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    Bellotti, A; Labbé, A; Fayol, N; El Mahtoufi, A; Baudouin, C

    2007-06-01

    Neovascular glaucoma is a chronic and sight-threatening disease. Four different grades have been described. Anterior chamber optical coherence tomography (OCT) is a new imaging technique allowing the visualization of the anterior segment. The purpose of our study was to describe the appearance of the different neovascular glaucoma grades with the OCT in order to refine the clinical analysis of this disease. Eleven patients (nine men and two women) with different grades of neovascular glaucoma were analyzed in this study. Neovascular glaucoma complicated central retinal vein occlusion in seven patients and diabetic retinopathy in four patients. All patients had bilateral biomicroscopical examination and OCT analysis. OCT images and clinical examination were then compared. No modifications could be observed using OCT in patients with grade 1 neovascular glaucoma. For grade 2, a slightly hyper-reflective linear iris secondary to neovascularization was observed. For grade 3, OCT images showed a thickened hyper-reflective iridocorneal angle with possible iridocorneal synechiae. For grade 4, the iridocorneal angle was closed and associated with iris contraction and uveae ectropion. OCT is a new promising technique for the precise analysis of different grades of neovascular glaucoma. It certainly helps in the management of such cases.

  18. A new animal model of choriodal neovascularization

    DEFF Research Database (Denmark)

    Kiilgaard, J.F.; Andersen, Mads V. Nis; Wiencke, A.K.

    2005-01-01

    ophthalmology, age-related macular degeneration, Bruch's membrane, retinal pigment epithelium, choroidal neovascularization, subretinal neovascularization......ophthalmology, age-related macular degeneration, Bruch's membrane, retinal pigment epithelium, choroidal neovascularization, subretinal neovascularization...

  19. Choroidal neovascular membrane

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    Bhatt Nitul; Diamond James; Jalali Subhadra; Das Taraprasad

    1998-01-01

    Choroidal neovascular membrane in the macular area is one of the leading causes of severe visual loss. Usually a manifestation in elderly population, it is often associated with age-related macular degeneration. The current mainstay of management is early diagnosis, usually by fundus examination, aided by angiography and photocoagulation in selected cases. Various other modalities of treatment including surgery are being considered as alternate options, but with limited success. The purpose o...

  20. Neovascularization in Purtscher's retinopathy

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    Chan A

    2011-11-01

    Full Text Available Annie Chan, Douglas R Fredrick, Theodore Leng Department of Ophthalmology, Byers Eye Institute at Stanford University, Stanford University School of Medicine, Stanford, CA, USA Abstract: We report a case of neovascularization secondary to Purtscher's retinopathy that showed minimal improvement with photocoagulation treatment. A 14-year-old boy with a history of cerebellar medulloblastoma presented with blurry vision and floaters after being struck by a motor vehicle while riding his bike. At presentation, visual acuity was 20/400 in his right eye and counting fingers in his left eye. Fundus examination showed disk edema, retinal whitening, and retinal hemorrhages in both eyes. Optical coherence tomography demonstrated thinning of the temporal retina and disruption of the inner segment–outer segment junction of the photoreceptor layer in the right eye and thickening and edema of the nasal macula, as well as a central foveal hyper-reflectivity, in the left eye. At the initial visit, there was no ischemia or neovascularization (NV. One month later, the patient developed NV of the disk and ischemia in the mid-periphery of the left eye. The patient underwent treatment with pan-retinal photocoagulation. The NV regressed, but visual outcome remained poor at his 5-month follow-up visit. Keywords: Purtscher's retinopathy, neovascularization, laser photocoagulation, disk edema

  1. Choroidal neovascular membrane

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    Bhatt Nitul

    1998-01-01

    Full Text Available Choroidal neovascular membrane in the macular area is one of the leading causes of severe visual loss. Usually a manifestation in elderly population, it is often associated with age-related macular degeneration. The current mainstay of management is early diagnosis, usually by fundus examination, aided by angiography and photocoagulation in selected cases. Various other modalities of treatment including surgery are being considered as alternate options, but with limited success. The purpose of this review is to briefly outline the current concepts and the management strategy from a clinician′s viewpoint.

  2. Choroidal neovascular membrane.

    Science.gov (United States)

    Bhatt, N S; Diamond, J G; Jalali, S; Das, T

    1998-06-01

    Choroidal neovascular membrane in the macular area is one of the leading causes of severe visual loss. Usually a manifestation in elderly population, it is often associated with age-related macular degeneration. The current mainstay of management is early diagnosis, usually by fundus examination, aided by angiography and photocoagulation in selected cases. Various other modalities of treatment including surgery are being considered as alternate options, but with limited success. The purpose of this review is to briefly outline the current concepts and the management strategy from a clinician's viewpoint.

  3. Biology and flow cytometry of proangiogenic hematopoietic progenitors cells.

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    Rose, Jonathan A; Erzurum, Serpil; Asosingh, Kewal

    2015-01-01

    During development, hematopoiesis and neovascularization are closely linked to each other via a common bipotent stem cell called the hemangioblast that gives rise to both hematopoietic cells and endothelial cells. In postnatal life, this functional connection between the vasculature and hematopoiesis is maintained by a subset of hematopoietic progenitor cells endowed with the capacity to differentiate into potent proangiogenic cells. These proangiogenic hematopoietic progenitors comprise a specific subset of bone marrow (BM)-derived cells that homes to sites of neovascularization and possess potent paracrine angiogenic activity. There is emerging evidence that this subpopulation of hematopoietic progenitors plays a critical role in vascular health and disease. Their angiogenic activity is distinct from putative "endothelial progenitor cells" that become structural cells of the endothelium by differentiation into endothelial cells. Proangiogenic hematopoietic progenitor cell research requires multidisciplinary expertise in flow cytometry, hematology, and vascular biology. This review provides a comprehensive overview of proangiogenic hematopoietic progenitor cell biology and flow cytometric methods to detect these cells in the peripheral blood circulation and BM. © 2014 International Society for Advancement of Cytometry.

  4. CCR7 signaling pathway and retinal neovascularization

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    Lin-Hui Yuan

    2015-11-01

    Full Text Available Retinal neovascularization diseases are the major causes of blindness. C-C chemokine receptor type 7(CCR7can promote the expression of vascular endothelial growth factor(VEGFthrough the extracellular signal regulated kinase(ERKpathway, leading to vascular leakage, proliferation of vascular endothelial cell, neovascularization and etc. The detection of CCR7 can guide the diagnosis and treatments of retinal neovascularization diseases.

  5. Neovascularization of the iris in retinoschisis

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    Geraldine R. Slean

    2017-09-01

    Conclusions and importance: Chronic bullous retinoschisis can be associated with anterior segment neovascularization such as rubeosis iridis, presumably due to non-perfusion within the retinoschisis cavity.

  6. Progenitor Epithelium

    Science.gov (United States)

    Marty-Santos, Leilani

    2015-01-01

    Insulin-producing β cells within the vertebrate fetal pancreas acquire their fate in a step-wise manner. Whereas the intrinsic factors dictating the transcriptional or epigenetic status of pancreatic lineages have been intensely examined, less is known about cell–cell interactions that might constitute a niche for the developing β cell lineage. It is becoming increasingly clear that understanding and recapitulating these steps may instruct in vitro differentiation of embryonic stem cells and/or therapeutic regeneration. Indeed, directed differentiation techniques have improved since transitioning from 2D to 3D cultures, suggesting that the 3D microenvironment in which β cells are born is critical. However, to date, it remains unknown whether the changing architecture of the pancreatic epithelium impacts the fate of cells therein. An emerging challenge in the field is to elucidate how progenitors are allocated during key events, such as the stratification and subsequent resolution of the pre-pancreatic epithelium, as well as the formation of lumens and branches. Here, we assess the progenitor epithelium and examine how it might influence the emergence of pancreatic multipotent progenitors (MPCs), which give rise to β cells and other pancreatic lineages. PMID:26216134

  7. A new animal model of choroidal neovascularization

    DEFF Research Database (Denmark)

    Kiilgaard, Jens Folke; Andersen, Mads Varis Nis; Wiencke, Anne

    2005-01-01

    The purpose of this study was to evaluate the ability of different methods to induce choroidal neovascularization (CNV) in the domestic pig.......The purpose of this study was to evaluate the ability of different methods to induce choroidal neovascularization (CNV) in the domestic pig....

  8. Human tears reveal insights into corneal neovascularization.

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    Zakaria, Nadia; Van Grasdorff, Sigi; Wouters, Kristien; Rozema, Jos; Koppen, Carina; Lion, Eva; Cools, Nathalie; Berneman, Zwi; Tassignon, Marie-José

    2012-01-01

    Corneal neovascularization results from the encroachment of blood vessels from the surrounding conjunctiva onto the normally avascular cornea. The aim of this study is to identify factors in human tears that are involved in development and/or maintenance of corneal neovascularization in humans. This could allow development of diagnostic tools for monitoring corneal neovascularization and combination monoclonal antibody therapies for its treatment. In an observational case-control study we enrolled a total of 12 patients with corneal neovascularization and 10 healthy volunteers. Basal tears along with reflex tears from the inferior fornix, superior fornix and using a corneal bath were collected along with blood serum samples. From all patients, ocular surface photographs were taken. Concentrations of the pro-angiogenic cytokines interleukin (IL)-6, IL-8, Vascular Endothelial Growth Factor (VEGF), Monocyte Chemoattractant Protein 1 (MCP-1) and Fas Ligand (FasL) were determined in blood and tear samples using a flow cytometric multiplex assay. Our results show that the concentration of pro-angiogenic cytokines in human tears are significantly higher compared to their concentrations in serum, with highest levels found in basal tears. Interestingly, we could detect a significantly higher concentration of IL- 6, IL-8 and VEGF in localized corneal tears of patients with neovascularized corneas when compared to the control group. This is the first study of its kind demonstrating a significant difference of defined factors in tears from patients with neovascularized corneas as compared to healthy controls. These results provide the basis for future research using animal models to further substantiate the role of these cytokines in the establishment and maintenance of corneal neovascularization.

  9. Pulpal progenitors and dentin repair.

    Science.gov (United States)

    Harichane, Y; Hirata, A; Dimitrova-Nakov, S; Granja, I; Goldberg, A; Kellermann, O; Poliard, A

    2011-07-01

    Mesenchymal stem cells are present in the dental pulp. They have been shown to contribute to dentin-like tissue formation in vitro and to participate in bone repair after a mandibular lesion. However, their capacity to contribute efficiently to reparative dentin formation after pulp lesion has never been explored. After pulp exposure, we have identified proliferative cells within 3 zones. In the crown, zone I is near the cavity, and zone II corresponds to the isthmus between the mesial and central pulp. In the root, zone III, near the apex, at a distance from the inflammatory site, contains mitotic stromal cells which may represent a source of progenitor cells. Stem-cell-based strategies are promising treatments for tissue injury in dentistry. Our experiments focused on (1) location of stem cells induced to leave their quiescent state early after pulp injury and (2) implantation of pulp progenitors, a substitute for classic endodontic treatments, paving the way for pulp stem-cell-based therapies.

  10. Host immune cellular reactions in corneal neovascularization

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    Nizar S. Abdelfattah

    2016-04-01

    Full Text Available Corneal neovascularization (CNV is a global important cause of visual impairment. The immune mechanisms leading to corneal heme- and lymphangiogenesis have been extensively studied over the past years as more attempts were made to develop better prophylactic and therapeutic measures. This article aims to discuss immune cells of particular relevance to CNV, with a focus on macrophages, Th17 cells, dendritic cells and the underlying immunology of common pathologies involving neovascularization of the cornea. Hopefully, a thorough understanding of these topics would propel the efforts to halt the detrimental effects of CNV.

  11. The Use of Endothelial Progenitor Cells for the Regeneration of Musculoskeletal and Neural Tissues

    OpenAIRE

    Kamei, Naosuke; Atesok, Kivanc; Ochi, Mitsuo

    2017-01-01

    Endothelial progenitor cells (EPCs) derived from bone marrow and blood can differentiate into endothelial cells and promote neovascularization. In addition, EPCs are a promising cell source for the repair of various types of vascularized tissues and have been used in animal experiments and clinical trials for tissue repair. In this review, we focused on the kinetics of endogenous EPCs during tissue repair and the application of EPCs or stem cell populations containing EPCs for tissue regenera...

  12. Type 3 Neovascularization Associated with Retinitis Pigmentosa.

    Science.gov (United States)

    Sayadi, Jihene; Miere, Alexandra; Souied, Eric H; Cohen, Salomon Y

    2017-01-01

    To report a case of type 3 neovascular lesion in a patient with retinitis pigmentosa (RP) complicated by macular edema. A 78-year-old man with a long follow-up for RP was referred for painless visual acuity decrease in the right eye. Best-corrected visual acuity was 20/125 in the right eye and 20/40 in the left. Fundus examination showed typical RP and macular edema in both eyes. In the right eye, spectral domain optical coherence tomography revealed a marked cystic macular edema associated with disruption of the Bruch membrane/retinal pigment epithelium complex overlying a pigmentary epithelium detachment, with a vascular structure which appeared to originate from the deep capillary plexus and to be connected with the subretinal pigment epithelium space. Optical coherence tomography angiography showed a high-flow vessel infiltrating the outer retinal layers in the deep capillary plexus segmentation, and a tuft-shaped, bright, high-flow network that seemed to be connected with the subretinal pigment epithelium space in the outer retinal layer segmentation. This presentation was consistent with an early type 3 neovascular lesion in the right eye. Type 3 neovascularization may be considered a possible complication of RP.

  13. Type 3 Neovascularization Associated with Retinitis Pigmentosa

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    Jihene Sayadi

    2017-04-01

    Full Text Available Purpose: To report a case of type 3 neovascular lesion in a patient with retinitis pigmentosa (RP complicated by macular edema. Case Report: A 78-year-old man with a long follow-up for RP was referred for painless visual acuity decrease in the right eye. Best-corrected visual acuity was 20/125 in the right eye and 20/40 in the left. Fundus examination showed typical RP and macular edema in both eyes. In the right eye, spectral domain optical coherence tomography revealed a marked cystic macular edema associated with disruption of the Bruch membrane/retinal pigment epithelium complex overlying a pigmentary epithelium detachment, with a vascular structure which appeared to originate from the deep capillary plexus and to be connected with the subretinal pigment epithelium space. Optical coherence tomography angiography showed a high-flow vessel infiltrating the outer retinal layers in the deep capillary plexus segmentation, and a tuft-shaped, bright, high-flow network that seemed to be connected with the subretinal pigment epithelium space in the outer retinal layer segmentation. This presentation was consistent with an early type 3 neovascular lesion in the right eye. Conclusion: Type 3 neovascularization may be considered a possible complication of RP.

  14. Purtscher's retinopathy followed by neovascular glaucoma

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    Kuroda M

    2013-11-01

    Full Text Available Masasko Kuroda,1 Akihiro Nishida,1 Masashi Kikuchi,2 Yasuo Kurimoto11Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan; 2Kikuchi Eye Clinic, Kobe, Hyogo, JapanAbstract: We report the case of a 66-year-old Japanese man who developed neovascular glaucoma secondary to Purtscher's retinopathy following a head injury. The patient presented at our hospital with blurred vision and a visual field abnormality in his left eye 1 month after suffering from a head injury. Upon initial presentation, his best-corrected visual acuity on a decimal chart was 1.5 oculus dexter and 0.6 oculus sinister. The intraocular pressure (IOP was 12 mmHg in both eyes. Fundus examination of the left eye revealed multiple white lesions in the posterior pole. Optical coherence tomography demonstrated retinal edema, particularly in the inner retina. On the basis of these findings, a diagnosis of Purtscher's retinopathy was made. One month after the initial examination, the visual acuity in the left eye deteriorated to 0.01 in decimal chart, and the IOP increased to 37 mmHg. Gonioscopy showed angle neovascularization. The patient received an intravitreal bevacizumab injection and panretinal photocoagulation. Subsequently, the IOP normalized and the angle neovascularization regressed.Keywords: blurred vision, visual field, retinal edema, head injury, head trauma

  15. Photoacoustic detection of neovascularities in skin graft

    Science.gov (United States)

    Yamazaki, Mutsuo; Sato, Shunichi; Saitoh, Daizo; Ishihara, Miya; Okada, Yoshiaki; Ashida, Hiroshi; Obara, Minoru

    2005-04-01

    We previously proposed a new method for monitoring adhesion of skin graft by measuring photoacoustic (PA) signal originated from the neovascularities. In this study, immunohistochemical staining (IHC) with CD31 antibody was performed for grafted skin tissue to observe neovascularity, and the results were compared with PA signals. We also used a laser Doppler imaging (LDI) to observe blood flow in the grafted skin, and sensitivity of PA measurement and that of LDI were compared. In rat autograft models, PA signals were measured for the grafted skin at postgrafting times of 0-48 h. At 6 h postgrafting, PA signal was observed in the skin depth region of 500-600 mm, while the results of IHC showed that angiogenesis occurred at the depth of about 600 mm. Depths at which PA signal and angiogenesis were observed decreased with postgrafting time. These indicate that the PA signal observed at 6 h postgrafting originated from the neovascularities in the skin graft. Results of LDI showed no blood-originated signal before 48 h postgrafting. These findings suggest that PA measurement is effective in monitoring the adhesion of skin graft in early stage after transplantation.

  16. Pachychoroid neovasculopathy in extramacular choroidal neovascularization

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    Gupta MP

    2016-07-01

    Full Text Available Mrinali Patel Gupta, Irene Rusu, Carly Seidman, Anton Orlin, Donald J D’Amico, Szilard Kiss Department of Ophthalmology, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, USA Purpose: To review a series of extramacular choroidal neovascular membranes (CNVMs in the context of their choroidal features, as determined by optical coherence tomography (OCT.Methods: Patients with extramacular CNVMs were identified from a tertiary care center through a review of records. The charts and cases were reviewed using multimodal imaging including fundus photography, OCT, fluorescein angiography (FA, and indocyanine angio­graphy (ICG.Results: Of six patients with extramacular CNVMs evaluated in this series, four patients (66.7% exhibited pachychoroidopathy on OCT imaging under or adjacent to the extramacular CNVM. All four of these patients also exhibited pachychoroidopathy in the macular OCT distant from the CNVM.Conclusion: Pachychoroidopathy is implicated in some cases of extramacular CNVMs. This represents the first report, to our knowledge, of pachychoroidopathy in extramacular CNVM. Keywords: choroidal neovascularization, pachychoroidopathy, pachychoroid neovasculopathy, peripheral disciform lesions, extramacular choroidal neovascularization, polypoidal choroidal vasculopathy

  17. Erythropoietin Receptor Positive Circulating Progenitor Cells and Endothelial Progenitor Cells in Patients with Different Stages of Diabetic Retinopathy

    Institute of Scientific and Technical Information of China (English)

    Liu-mei Hu; Guo-xu Xu; Guo-tong XU; Wei-ye Li; Xia Lei; Bo Ma; Yu Zhang; Yan Yan; Ya-lan Wu; Ge-zhi Xu; Wen Ye; Ling Wang

    2011-01-01

    Objective To investigate the possible involvement of erythropoietin (EPO)/erythropoietin receptor(EPOR) system in neovascularization and vascular regeneration in diabetic retinopathy (DR).Methods EPOR positive circulating progenitor cells (CPCs: CD34+) and endothelial progenitor cells (EPCs: CD34+KDR+) were assessed by flow cytometry in type 2 diabetic patients with different stages of DR. The cohort consisted of age- and sex-matched control patients without diabetes (n=7), non-prolif-erative DR (NPDR, n=7), proliferative DR (PDR, n=8), and PDR complicated with diabetic nephropathy (PDR-DN, n=7). Results The numbers of EPOR+ CPCs and EPOR+ EPCs were reduced remarkably in NPDR compared with the control group (both P<0.01), whereas rebounded in PDR and PDR-DN groups in varying degrees. Similar changes were observed in respect of the proportion of EPOR+ CPCs in CPCs (NPDR vs.control, P< 0.01) and that of EPOR+ EPCs in EPCs (NPDR vs. control, P< 0.05). Conclusion Exogenous EPO, mediated via the EPO/EPOR system of EPCs, may alleviate the im-paired vascular regeneration in NPDR, whereas it might aggravate retinal neovascularization in PDR due to a rebound of EPOR+ EPCs associated with ischemia.

  18. Podoplanin-expressing Cells Derived from Bone Marrow Play a Crucial Role in Postnatal Lymphatic Neovascularization

    Science.gov (United States)

    Lee, Ji Yoon; Park, Changwon; Cho, Yong Pil; Lee, Eugine; Kim, Hyongbum; Kim, Pilhan; Yun, Seok H.; Yoon, Young-sup

    2010-01-01

    Background Emerging evidence has suggested a contribution of bone marrow (BM) cells to lymphatic vessel formation; however, the exact phenotype of the cells with lymphatic endothelial progenitor cell (LEPC) function has yet to be identified. Here we investigate the identity of BM-derived LEPCs and their role in lymphatic neovascularization. Methods and Results Culture of BM-mononuclear cells (MNCs) in the presence of VEGFA, VEGFC and EGF resulted in expression of lymphatic endothelial cell (LEC) markers. Among these cells, podoplanin+ cells were isolated by magnetic-labeled cell separation system (MACS) and characterized by FACS and immunocytochemistry. These podoplanin+ cells highly express markers for LECs, hematopoietic lineages, and stem/progenitor cells, and upon further cultivation, generate LECs. We further confirmed that podoplanin+ cells exist in small numbers in BM and peripheral blood (PB) of normal mice, but are significantly (15 fold) augmented upon lymphangiogenic stimuli such as tumor implantation. Next, to evaluate the potential of podoplanin+ cells for the formation of new lymphatic vessels in vivo, we injected culture-isolated or freshly isolated BM-derived podoplanin+ cells into wound and tumor models. Immunohistochemistry demonstrated that the injected cells were incorporated into the lymphatic vasculature, displayed LEC phenotypes, and increased lymphatic vascular density in tissues, suggesting lymphvasculogenesis. Podoplanin+ cells also expressed high levels of lymphangiogenic cytokines and increased proliferation of LECs during co-culture, suggesting a lymphangiogenic or paracrine role. Conclusions Our results provide compelling evidence that BM-derived podoplanin+ cells, a previously unrecognized cell type, function as LEPCs and participate in postnatal lymphatic neovascularization through both lymphvasculogenesis and lymphangiogenesis. PMID:20855662

  19. Subretinal neovascularization from the retina in radiation retinopathy

    International Nuclear Information System (INIS)

    Boozalis, G.T.; Schachat, A.P.; Green, W.R.

    1987-01-01

    In a 66-year-old woman with radiation retinopathy, subretinal neovascularization was present, originating from telangiectatic retinal vessels in the macular area. The patient showed no clinical or histologic evidence of age-related macular degeneration or other conditions that may have contributed to the subretinal neovascularization

  20. Type 1 neovascularization with polypoidal lesions complicating dome shaped macula

    OpenAIRE

    Naysan, Jonathan; Dansingani, Kunal K; Balaratnasingam, Chandrakumar; Freund, K Bailey

    2015-01-01

    Dome-shaped macula is described as an inward bulge of the macula within a posterior staphyloma in highly myopic eyes. Choroidal neovascularization is a known complication that can cause visual loss in dome-shaped macula. Herein, we describe a patient who presented with features of polypoidal choroidal neovascularization that developed on a background of high myopia with dome-shaped macula.

  1. Research on inhibition of corneal neovascularization

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    Zhang-Hui Yang

    2015-12-01

    Full Text Available Corneal transparency is the basis of the normal physiological functions.However, corneal neovascularization(CNVmay occur in the infection, mechanical and chemical injury or under other pathological conditions,which make the cornea lose original transparency and severe visual impairment. In recent years, along with the development of immunology, molecular biology, biochemistry and other disciplines, there is more in-depth understanding on the CNV, and clinical treatment of CNV has made new breakthroughs. This article provides an overview of the inhibition of CNV.

  2. Lonafarnib is a potential inhibitor for neovascularization.

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    Linlin Sun

    Full Text Available Atherosclerosis is a common cardiovascular disease that involves the build-up of plaque on the inner walls of the arteries. Intraplaque neovacularization has been shown to be essential in the pathogenesis of atherosclerosis. Previous studies showed that small-molecule compounds targeting farnesyl transferase have the ability to prevent atherosclerosis in apolipoprotein E-deficient mice, but the underlying mechanism remains to be elucidated. In this study, we found that lonafarnib, a specific inhibitor of farnesyl transferase, elicits inhibitory effect on vascular endothelial capillary assembly in vitro in a dose-dependent manner. In addition, we showed that lonafarnib treatment led to a dose-dependent decrease in scratch wound closure in vitro, whereas it had little effect on endothelial cell proliferation. These data indicate that lonafarnib inhibits neovascularization via directly targeting endothelial cells and disturbing their motility. Moreover, we demonstrated that pharmacological inhibition of farnesyl transferase by lonafarnib significantly impaired centrosome reorientation toward the leading edge of endothelial cells. Mechanistically, we found that the catalytic β subunit of farnesyl transferase associated with a cytoskeletal protein important for the establishment and maintenance of cell polarity. Additionally, we showed that lonafarnib remarkably inhibited the expression of the cytoskeletal protein and interrupted its interaction with farnesyl transferase. Our findings thus offer novel mechanistic insight into the protective effect of farnesyl transferase inhibitors on atherosclerosis and provide encouraging evidence for the potential use of this group of agents in inhibiting plaque neovascularization.

  3. Homoisoflavonoids as potential antiangiogenic agents for retinal neovascularization.

    Science.gov (United States)

    Amin, Sk Abdul; Adhikari, Nilanjan; Gayen, Shovanlal; Jha, Tarun

    2017-11-01

    A number of people worldwide have been suffering from ocular neovascularization that may be treated by a variety of drugs but these may possess adverse effects. Therefore, small antiangiogenic molecules with higher potency and lower toxic effects are intended. However, homoisoflavonoids of natural origin show the potential antiangiogenic effect in ocular neovascularization. These homoisoflavonoids are judged quantitatively in terms of statistical validation through multi-chemometric modeling approaches for the betterment and refinement of their structures required for higher antiangiogenic activity targeted to ocular neovascularization. These approaches may be utilized to design better antiangiogenic homoisoflavonoids. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Targeting Neovascularization in Ischemic Retinopathy: Recent Advances

    Science.gov (United States)

    Al-Shabrawey, Mohamed; Elsherbiny, Mohamed; Nussbaum, Julian; Othman, Amira; Megyerdi, Sylvia; Tawfik, Amany

    2014-01-01

    Pathological retinal neovascularization (RNV) is a common micro-vascular complication in several retinal diseases including retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration and central vein occlusion. The current therapeutic modalities of RNV are invasive and although they may slow or halt the progression of the disease they are unlikely to restore normal acuity. Therefore, there is an urgent need to develop treatment modalities, which are less invasive and therefore associated with fewer procedural complications and systemic side effects. This review article summarizes our understanding of the pathophysiology and current treatment of RNV in ischemic retinopathies; lists potential therapeutic targets; and provides a framework for the development of future treatment modalities. PMID:25598837

  5. Beals–Hecht syndrome and choroidal neovascularization

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    Roberto Gallego-Pinazo

    2010-07-01

    Full Text Available Roberto Gallego-Pinazo1, Ruth López-Lizcano1, José María Millán2,3, J Fernando Arevalo5, J Luis Mullor6, Manuel Díaz-Llopis1,3,41Department of Ophthalmology, 2Department of Genetics, Unit of Experimental Opthalmology, Hospital Universitario La Fe, Valencia, Spain; 3Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Valencia, Spain; 4Faculty of Medicine, University of Valencia, Valencia, Spain; 5Retina and Vitreous Service, Clínica Oftalmológica Centro Caracas, Caracas, Venezuela; 6Unit of Experimental Opthalmology, Fundación Parala Investigación del Hospital La Fe, Valencia, SpainPurpose: To describe a case of choroidal neovascularization (CNV in a female diagnosed with Beals–Hecht syndrome.Methods: A retrospective, interventional case is described in a 26-year-old female complaining of metamorphopsia and visual loss in her left eye (counting fingers. The fluorescein angiogram and the optical coherence tomography supported the diagnosis of CNV. Intravitreal ranibizumab was administered.Results: After the third intravitreal ranibizumab, her visual acuity improved to 0.8 and the morphology of the macular area was restored.Conclusions: To our knowledge this is the first report of CNV in Beals–Hecht syndrome treated with ranibizumab. Self-monitoring by periodically performing Amsler grid test is strongly recommended in these patients in order to achieve an early diagnosis of eventual CNV and avoid visual acuity loss.Keywords: Beals–Hecht syndrome, connective tissue disease, choroidal neovascularization, ranibizumab

  6. Progress of stem/progenitor cell-based therapy for retinal degeneration.

    Science.gov (United States)

    Tang, Zhimin; Zhang, Yi; Wang, Yuyao; Zhang, Dandan; Shen, Bingqiao; Luo, Min; Gu, Ping

    2017-05-10

    Retinal degeneration (RD), such as age-related macular degeneration (AMD) and retinitis pigmentosa, is one of the leading causes of blindness. Presently, no satisfactory therapeutic options are available for these diseases principally because the retina and retinal pigmented epithelium (RPE) do not regenerate, although wet AMD can be prevented from further progression by anti-vascular endothelial growth factor therapy. Nevertheless, stem/progenitor cell approaches exhibit enormous potential for RD treatment using strategies mainly aimed at the rescue and replacement of photoreceptors and RPE. The sources of stem/progenitor cells are classified into two broad categories in this review, which are (1) ocular-derived progenitor cells, such as retinal progenitor cells, and (2) non-ocular-derived stem cells, including embryonic stem cells, induced pluripotent stem cells, and mesenchymal stromal cells. Here, we discuss in detail the progress in the study of four predominant stem/progenitor cell types used in animal models of RD. A short overview of clinical trials involving the stem/progenitor cells is also presented. Currently, stem/progenitor cell therapies for RD still have some drawbacks such as inhibited proliferation and/or differentiation in vitro (with the exception of the RPE) and limited long-term survival and function of grafts in vivo. Despite these challenges, stem/progenitor cells represent the most promising strategy for RD treatment in the near future.

  7. ES-cell derived hematopoietic cells induce transplantation tolerance.

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    Sabrina Bonde

    Full Text Available BACKGROUND: Bone marrow cells induce stable mixed chimerism under appropriate conditioning of the host, mediating the induction of transplantation tolerance. However, their strong immunogenicity precludes routine use in clinical transplantation due to the need for harsh preconditioning and the requirement for toxic immunosuppression to prevent rejection and graft-versus-host disease. Alternatively, embryonic stem (ES cells have emerged as a potential source of less immunogenic hematopoietic progenitor cells (HPCs. Up till now, however, it has been difficult to generate stable hematopoietic cells from ES cells. METHODOLOGY/PRINCIPAL FINDINGS: Here, we derived CD45(+ HPCs from HOXB4-transduced ES cells and showed that they poorly express MHC antigens. This property allowed their long-term engraftment in sublethally irradiated recipients across MHC barriers without the need for immunosuppressive agents. Although donor cells declined in peripheral blood over 2 months, low level chimerism was maintained in the bone marrow of these mice over 100 days. More importantly, chimeric animals were protected from rejection of donor-type cardiac allografts. CONCLUSIONS: Our data show, for the first time, the efficacy of ES-derived CD45(+ HPCs to engraft in allogenic recipients without the use of immunosuppressive agents, there by protecting cardiac allografts from rejection.

  8. Neovascular glaucoma after helium ion irradiation for uveal melanoma

    International Nuclear Information System (INIS)

    Kim, M.K.; Char, D.H.; Castro, J.L.; Saunders, W.M.; Chen, G.T.; Stone, R.D.

    1986-01-01

    Neovascular glaucoma developed in 22 of 169 uveal melanoma patients treated with helium ion irradiation. Most patients had large melanomas; no eyes containing small melanomas developed anterior segment neovascularization. The mean onset of glaucoma was 14.1 months (range, 7-31 months). The incidence of anterior segment neovascularization increased with radiation dosage; there was an approximately three-fold increase at 80 GyE versus 60 GyE of helium ion radiation (23% vs. 8.5%) (P less than 0.05). Neovascular glaucoma occurred more commonly in larger tumors; the incidence was not affected by tumor location, presence of subretinal fluid, nor rate of tumor regression. Fifty-three percent of patients had some response with intraocular pressures of 21 mmHg or less to a combination of antiglaucoma treatments

  9. Inhibition of Corneal Neovascularization by Topical and Subconjunctival Tigecycline

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    Sertan Goktas

    2014-01-01

    Full Text Available Objective. To investigate the effects of topical and subconjunctival tigecycline on the prevention of corneal neovascularization. Materials and Methods. Following chemical burn, thirty-two rats were treated daily with topical instillation of 1 mg/mL tigecycline (group 1 or subconjunctival instillation of 1 mg/mL tigecycline (group 3 for 7 days. Control rats received topical (group 2 or subconjunctival (group 4 0.9% saline. Digital photographs of the cornea were taken on the eighth day after treatment and analyzed to determine the percentage area of the cornea covered by neovascularization. Corneal sections were analyzed histopathologically. Results. The median percentages of corneal neovascularization in groups 1 and 3 were 48% (95% confidence interval (CI, 44.2–55.8% and 33.5% (95% CI, 26.6–39.2%, respectively. The median percentages of corneal neovascularization of groups 1 and 3 were significantly lower than that of the control group (P=0.03 and P<0.001, resp.. Histologic examination of samples from groups 1 and 3 showed lower vascularity than that of control groups. Conclusion. Topical and subconjunctival administration of tigecycline seems to be showing promising therapeutic effects on the prevention of corneal neovascularization. Furthermore, subconjunctival administration of tigecycline is more potent than topical administration in the inhibition of corneal neovascularization.

  10. Neovascular events in eyes with central retinal vein occlusion undergoing serial bevacizumab or ranibizumab intravitreal injections: A retrospective review

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    Francis Char DeCroos

    2014-01-01

    Conclusion: Neovascular events occur in eyes with CRVO undergoing serial anti-VEGF therapy, and these events may be delayed compared to the natural history of CRVO-associated neovascularization. Iris neovascularization occurred most frequently.

  11. Study of surgical treatment on neovascular glaucoma

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    Xiao-Nü Liu

    2014-05-01

    Full Text Available AIM: To compare the effect of two surgical methods on neovascular glaucoma(NVG. METHODS: The clinical date of 46 cases(57 eyeswith NVG underwent surgical treatment were retrospectively analyzed and followed-up. Patients were divided into Ahmed glaucoma valve(AGVimplantation group(group A, 24 cases, 31 eyesand semiconductor diode laser transscleral ciliary body photocoagulation(TSCPCgroup(group B, 22cases, 26 eyesaccording to the surgical approach. The intraocular pressure, visual acuity and postoperative complications were compared before and after operation. RESULTS: The intraocular pressure postoperative in two groups were significantly lower than those preoperative(P P>0.05. The changes of visual acuity postoperative showed no statistical difference between the two groups(P>0.05. The postoperative complications of group A was significantly lower than that in group B, in which the incidence of eye pain, anterior chamber bleeding were significant differences between two groups(P CONCLUSION: AGV implantation treatment and TSCPC for NVG are both valid, but AGV implantation is filtration surgery, and TSCPC isciliary body destructive surgery, and the latter has higher rate of postoperative complications.

  12. Progenitors of white dwarfs

    International Nuclear Information System (INIS)

    Drilling, J.S.; Schoenberner, D.

    1985-01-01

    Direct observational evidence is presented which indicates that the immediate progenitors of white dwarfs are the central stars of planetary nebulae (approximately 70%), other post-AGB objects (approximately 30%), and post-HB objects not massive enough to climb the AGB (approximately 0.3%). The combined birth rate for these objects is in satisfactory agreement with the death rate of main-sequence stars and the birth rate of white dwarfs

  13. Clinical effect of neovascular glaucoma treated by vitrectomy and cyclophotocoagulation

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    Yi-Xuan Jin

    2014-07-01

    Full Text Available AIM: To observe the postoperative intraocular pressure(IOPand operation safety in the eyes of the neovascular glaucoma pateints treated by intraocular cyclophotocoagulation which needed vitrectomy at the same time. METHODS: A total of 12 neovascular glaucoma cases(14 eyessecondary to diabetic retinopathy, retinal detachment surgery and trauma were reviewed in our study. This procedure mainly used intraocular photocoagulation catheter to highlight the ciliary processes until the ciliary became white atrophy or plosion after vitreous surgery treatment. The intraocular photocoagulation catheter was performed at a power of 300-500mW, for a duration of 0.1-0.2ms. Postoperative follow-up was at least for 6mo. The observation of 14 postoperative neovascular glaucoma was performed at 1wk, 1, 6mo observing the IOP and complications. RESULTS: IOP of the 11 eyes was significantly declined and controlled in normal. After cyclophotocoagulation, average IOP at 1wk was 16.7±14.4mmHg, 15.7±8.8mmHg at 1mo and 12.9±4.5mmHg at 6mo, which compared with untreatment(39.6 ±10.0mmHgwas statistically significant different(PCONCLUSION: The intraocular cyclophotocoagulation and vitrectomy simultaneously can deal with the primary disease and secondary neovascular glaucoma. The operation can be accurately performed under direct cyclophotocoagulation and it is a safe and effective way for neovascular glaucoma which needs vitreous surgery.

  14. Parametric imaging of tumor perfusion and neovascular morphology using ultrasound

    Science.gov (United States)

    Hoyt, Kenneth

    2015-03-01

    A new image processing strategy is detailed for the simultaneous measurement of tumor perfusion and neovascular morphology parameters from a sequence of dynamic contrast-enhanced ultrasound (DCE-US) images. A technique for locally mapping tumor perfusion parameters using skeletonized neovascular data is also introduced. Simulated images were used to test the neovascular skeletonization technique and variance (error) of relevant parametric estimates. Preliminary DCE-US image datasets were collected in 6 female patients diagnosed with invasive breast cancer and using a Philips iU22 ultrasound system equipped with a L9-3 MHz transducer and Definity contrast agent. Simulation data demonstrates that neovascular morphology parametric estimation is reproducible albeit measurement error can occur at a lower signal-to-noise ratio (SNR). Experimental results indicate the feasibility of our approach to performing both tumor perfusion and neovascular morphology measurements from DCE-US images. Future work will expand on our initial clinical findings and also extent our image processing strategy to 3-dimensional space to allow whole tumor characterization.

  15. RETINAL NEOVASCULARIZATION FROM A PATIENT WITH CUTIS MARMORATA TELANGIECTATICA CONGENITA.

    Science.gov (United States)

    Sassalos, Thérèse M; Fields, Taylor S; Levine, Robert; Gao, Hua

    2018-03-14

    To report a rare case of peripheral retinal neovascularization in a patient diagnosed with cutis marmorata telangiectatica congenita (CMTC). Observational case report. A 16-year-old girl was referred to clinic for retinal evaluation. The patient had a clinical diagnosis of CMTC later confirmed by skin biopsy. Examination revealed temporal peripheral retinal sheathing, as well as lattice degeneration in both eyes. Wide-field fluorescein angiogram showed substantive peripheral retinal nonperfusion with evidence of vascular leakage from areas of presumed retinal neovascularization. The patient subsequently had pan retinal photocoagulation laser treatment to each eye without complication. Cutis marmorata telangiectatica congenita is a rare vascular condition known to affect multiple organ systems including the eyes. Although ocular manifestations of CMTC are rare, instances of congenital glaucoma, suprachoroidal hemorrhage, and bilateral total retinal detachments resulting in secondary neovascular glaucoma have been reported. Our patient demonstrates the first reported findings of peripheral nonperfusion and retinal neovascularization related to CMTC in a 16-year-old girl. We propose early retinal examination, wide-field fluorescein angiogram, and early pan retinal photocoagulation laser treatment in patients with peripheral nonperfusion and retinal neovascularization from CMTC.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  16. Radiation therapy for neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Robert Petrarca

    2011-01-01

    Full Text Available Robert Petrarca, Timothy L JacksonDepartment of Ophthalmology, King’s College Hospital NHS Foundation Trust, London, UKAbstract: Antivascular endothelial growth factor (anti-VEGF therapies represent the standard of care for most patients presenting with neovascular (wet age-related macular degeneration (neovascular AMD. Anti-VEGF drugs require repeated injections and impose a considerable burden of care, and not all patients respond. Radiation targets the proliferating cells that cause neovascular AMD, including fibroblastic, inflammatory, and endothelial cells. Two new neovascular AMD radiation treatments are being investigated: epimacular brachytherapy and stereotactic radiosurgery. Epimacular brachytherapy uses beta radiation, delivered to the lesion via a pars plana vitrectomy. Stereotactic radiosurgery uses low voltage X-rays in overlapping beams, directed onto the lesion. Feasibility data for epimacular brachytherapy show a greatly reduced need for anti-VEGF therapy, with a mean vision gain of 8.9 ETDRS letters at 12 months. Pivotal trials are underway (MERLOT, CABERNET. Preliminary stereotactic radiosurgery data suggest a mean vision gain of 8 to 10 ETDRS letters at 12 months. A large randomized sham controlled stereotactic radiosurgery feasibility study is underway (CLH002, with pivotal trials to follow. While it is too early to conclude on the safety and efficacy of epimacular brachytherapy and stereotactic radiosurgery, preliminary results are positive, and these suggest that radiation offers a more durable therapeutic effect than intraocular injections.Keywords: wet age-related macular degeneration, neovascular, radiation therapy, epimacular brachytherapy, stereotactic radiosurgery, anti-VEGF

  17. Ischemic Retinopathy and Neovascular Proliferation Secondary to Severe Head Injury

    Directory of Open Access Journals (Sweden)

    Muge Coban-Karatas

    2014-01-01

    Full Text Available We report a case with severe head trauma and perforating globe injury in one eye and ischemic retinopathy and neovascular proliferation in the other eye. A 37-year-old male was brought to the emergency department after a motor vehicle accident with severe maxillofacial trauma. Ophthalmic examination revealed hematoma of the left eyelids as well as traumatic rupture and disorganization of the left globe. On the right eye, anterior segment and fundoscopic examination were normal. Primary globe repair was performed. At postoperative one-month visit, the right eye revealed no pathology of the optic disc and macula but severe neovascularization in the temporal peripheral retina. The patient was diagnosed as ischemic retinopathy and neovascular proliferation due to head trauma.

  18. The formation of rats' choroidal neovascularization induced by acrolein

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    Guan-Feng Wang

    2016-04-01

    Full Text Available AIM:To investigate the formation of rats' choroidal neovascularization(CNVinduced by acrolein. METHODS:Twelve Sprague-Dawley rats were randomly divided into three groups. Acrolein 200μL(2.5 mg/kg/dwas poured into the rats' stomach for 4wk as acrolein 4wk and for 8wk as acrolein 8wk group. The same volume of fresh water was also done to the rats as the control group. Remove all eye balls and embed into paraffin with HE staining.RESLUTS:The RPE-Bruch membrane was intact with no obvious abnormality in the control group and acrolein 4wk group. Lost in the continuity of RPE and the movement of choroidal neovascularization were found in the acrolein 8wk. CONCLUSION:The long time use of acrolein can induce the formation of choroial neovascularization in rats.

  19. Curcumin induces therapeutic angiogenesis in a diabetic mouse hindlimb ischemia model via modulating the function of endothelial progenitor cells.

    Science.gov (United States)

    You, Jinzhi; Sun, Jiacheng; Ma, Teng; Yang, Ziying; Wang, Xu; Zhang, Zhiwei; Li, Jingjing; Wang, Longgang; Ii, Masaaki; Yang, Junjie; Shen, Zhenya

    2017-08-03

    Neovascularization is impaired in diabetes mellitus, which leads to the development of peripheral arterial disease and is mainly attributed to the dysfunction of endothelial progenitor cells (EPCs). Previous studies proved the promotional effect of curcumin on neovascularization in wound healing of diabetes. Thus, we hypothesize that curcumin could promote neovascularization at sites of hindlimb ischemia in diabetes and might take effect via modulating the function of EPCs. Streptozotocin-induced type 1 diabetic mice and nondiabetic mice both received unilateral hindlimb ischemic surgery. Curcumin was then administrated to the mice by lavage for 14 days consecutively. Laser Doppler perfusion imaging was conducted to demonstrate the blood flow reperfusion. Capillary density was measured in the ischemic gastrocnemius muscle. In addition, angiogenesis, migration, proliferation abilities, and senescence were determined in EPCs isolated from diabetic and nondiabetic mice. Quantitative PCR was then used to determine the mRNA expression of vascular endothelial growth factor (VEGF) and angiopoetin-1 (Ang-1) in EPCs. Curcumin application to type 1 diabetic mice significantly improved blood reperfusion and increased the capillary density in ischemic hindlimbs. The in-vitro study also revealed that the angiogenesis, migration, and proliferation abilities of EPCs and the number of senescent EPCs were reversed by curcumin application. Quantitative PCR confirmed the overexpression of VEGF-A and Ang-1 in EPCs after curcumin treatment. Curcumin could enhance neovascularization via promoting the function of EPCs in a diabetic mouse hindlimb ischemia model.

  20. Masses of supernova progenitors

    International Nuclear Information System (INIS)

    Tinsley, B.M.

    1977-01-01

    The possible nature and masses of supernovae progenitors, and the bearing of empirical results on some unsolved theoretical problems concerning the origin of supernovae, are discussed. The author concentrates on two main questions: what is the lower mass limit for stars to die explosively and what stars initiate type I supernovae. The evidence considered includes local supernova rates, empirical estimates of msub(w) (the upper mass limit for death as a white dwarf), the distributions of supernovae among stellar populations in galaxies and the colors of supernova producing galaxies. (B.D.)

  1. The Use of Endothelial Progenitor Cells for the Regeneration of Musculoskeletal and Neural Tissues

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    Naosuke Kamei

    2017-01-01

    Full Text Available Endothelial progenitor cells (EPCs derived from bone marrow and blood can differentiate into endothelial cells and promote neovascularization. In addition, EPCs are a promising cell source for the repair of various types of vascularized tissues and have been used in animal experiments and clinical trials for tissue repair. In this review, we focused on the kinetics of endogenous EPCs during tissue repair and the application of EPCs or stem cell populations containing EPCs for tissue regeneration in musculoskeletal and neural tissues including the bone, skeletal muscle, ligaments, spinal cord, and peripheral nerves. EPCs can be mobilized from bone marrow and recruited to injured tissue to contribute to neovascularization and tissue repair. In addition, EPCs or stem cell populations containing EPCs promote neovascularization and tissue repair through their differentiation to endothelial cells or tissue-specific cells, the upregulation of growth factors, and the induction and activation of endogenous stem cells. Human peripheral blood CD34(+ cells containing EPCs have been used in clinical trials of bone repair. Thus, EPCs are a promising cell source for the treatment of musculoskeletal and neural tissue injury.

  2. Establishment of a tumor neovascularization animal model with biomaterials in rabbit corneal pouch.

    Science.gov (United States)

    Chu, Yu-Ping; Li, Hong-Chuan; Ma, Ling; Xia, Yang

    2018-06-01

    The present animal model of tumor neovascularization most often used by researchers is zebrafish. For studies on human breast cancer cell neovascularization, a new animal model was established to enable a more convenient study of tumor neovascularization. A sodium alginate-gelatin blend gel system was used to design the new animal model. The model was established using rabbit corneal pouch implantation. Then, the animal model was validated by human breast cancer cell lines MCF-7-Kindlin-2 and MCF-7-CMV. The experiment intuitively observed the relationship between tumor and neovascularization, and demonstrated the advantages of this animal model in the study of tumor neovascularization. The use of sodium alginate-gelatin blends to establish tumor neovascularization in a rabbit corneal pouch is a novel and ideal method for the study of neovascularization. It may be a better animal model for expanding the research in this area. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Results of laser treatment for sub-retinal neovascular membranes ...

    African Journals Online (AJOL)

    A retrospective study was carried out to determine the results of laser treatment for choroidal neovascular membranes in age-related macular degeneration in 92 patients in whom fluorescein angiography was performed for this condition over a 7-year period. Twenty-nine of these patients, treated with the argon laser, were ...

  4. Role of liver progenitors in liver regeneration.

    Science.gov (United States)

    Best, Jan; Manka, Paul; Syn, Wing-Kin; Dollé, Laurent; van Grunsven, Leo A; Canbay, Ali

    2015-02-01

    During massive liver injury and hepatocyte loss, the intrinsic regenerative capacity of the liver by replication of resident hepatocytes is overwhelmed. Treatment of this condition depends on the cause of liver injury, though in many cases liver transplantation (LT) remains the only curative option. LT for end stage chronic and acute liver diseases is hampered by shortage of donor organs and requires immunosuppression. Hepatocyte transplantation is limited by yet unresolved technical difficulties. Since currently no treatment is available to facilitate liver regeneration directly, therapies involving the use of resident liver stem or progenitor cells (LPCs) or non-liver stem cells are coming to fore. LPCs are quiescent in the healthy liver, but may be activated under conditions where the regenerative capacity of mature hepatocytes is severely impaired. Non-liver stem cells include embryonic stem cells (ES cells) and mesenchymal stem cells (MSCs). In the first section, we aim to provide an overview of the role of putative cytokines, growth factors, mitogens and hormones in regulating LPC response and briefly discuss the prognostic value of the LPC response in clinical practice. In the latter section, we will highlight the role of other (non-liver) stem cells in transplantation and discuss advantages and disadvantages of ES cells, induced pluripotent stem cells (iPS), as well as MSCs.

  5. Broad spectrum antiangiogenic treatment for ocular neovascular diseases.

    Directory of Open Access Journals (Sweden)

    Ofra Benny

    2010-09-01

    Full Text Available Pathological neovascularization is a hallmark of late stage neovascular (wet age-related macular degeneration (AMD and the leading cause of blindness in people over the age of 50 in the western world. The treatments focus on suppression of choroidal neovascularization (CNV, while current approved therapies are limited to inhibiting vascular endothelial growth factor (VEGF exclusively. However, this treatment does not address the underlying cause of AMD, and the loss of VEGF's neuroprotective can be a potential side effect. Therapy which targets the key processes in AMD, the pathological neovascularization, vessel leakage and inflammation could bring a major shift in the approach to disease treatment and prevention. In this study we have demonstrated the efficacy of such broad spectrum antiangiogenic therapy on mouse model of AMD.Lodamin, a polymeric formulation of TNP-470, is a potent broad-spectrum antiangiogenic drug. Lodamin significantly reduced key processes involved in AMD progression as demonstrated in mice and rats. Its suppressive effects on angiogenesis, vascular leakage and inflammation were studied in a wide array of assays including; a Matrigel, delayed-type hypersensitivity (DTH, Miles assay, laser-induced CNV and corneal micropocket assay. Lodamin significantly suppressed the secretion of various pro-inflammatory cytokines in the CNV lesion including monocyte chemotactic protein-1 (MCP-1/Ccl2. Importantly, Lodamin was found to regress established CNV lesions, unlike soluble fms-like tyrosine kinase-1 (sFlk-1. The drug was found to be safe in mice and have little toxicity as demonstrated by electroretinography (ERG assessing retinal and by histology.Lodamin, a polymer formulation of TNP-470, was identified as a first in its class, broad-spectrum antiangiogenic drug that can be administered orally or locally to treat corneal and retinal neovascularization. Several unique properties make Lodamin especially beneficial for ophthalmic

  6. Sickle cell-induced ischemic colitis.

    Science.gov (United States)

    Stewart, Camille L; Ménard, Geraldine E

    2009-07-01

    Sickle cell-induced ischemic colitis is a rare yet potentially fatal complication of sickle cell anemia. Frequent pain crises with heavy analgesia may obscure and prolong this important diagnosis. Our patient was a 29-year-old female with sickle cell disease who was admitted with left lower quadrant abdominal pain. A diagnostic workup, including chemistries, complete blood count, blood cultures, chest x-ray, computerized tomography scanning, and colonoscopy, was performed to identify the etiology of her symptoms. This case highlights the importance of differentiating simple pain crisis from more serious and life-threatening ischemic bowel. A review of the literature compares this case to others reported and gives a method for diagnosing and treating this complication of sickle cell disease.

  7. Current and emerging treatment options for myopic choroidal neovascularization

    Directory of Open Access Journals (Sweden)

    El Matri L

    2015-04-01

    Full Text Available Leila El Matri, Ahmed Chebil, Fedra Kort Department B of Ophthalmology, Hedi Rais Institute of Ophthalmology, Faculty of Medicine of Tunis, University of El Manar, Tunis, Tunisia Abstract: Choroidal neovascularization (CNV is the main cause of visual impairment in highly myopic patients younger than 50 years of age. There are different treatments for myopic CNV (mCNV, with 5- to 10-year outcomes currently. Chorioretinal atrophy is still the most important determinant factor for visual outcome. The purpose of this study is to provide an overview of the current treatments for mCNV, including laser, surgical management, verteporfin photodynamic therapy, and mainly anti-vascular endothelial growth factor therapy. Emerging treatment options are also discussed. Keywords: myopia, choroidal neovascularization, current treatment, emerging treatment

  8. PPAR Agonists: Potential as Therapeutics for Neovascular Retinopathies

    Directory of Open Access Journals (Sweden)

    Harrihar A. Pershadsingh

    2008-01-01

    Full Text Available The angiogenic, neovascular proliferative retinopathies, proliferative diabetic retinopathy (PDR, and age-dependent macular degeneration (AMD complicated by choroidal neovascularization (CNV, also termed exudative or “wet” AMD, are common causes of blindness. The antidiabetic thiazolidinediones (TZDs, rosiglitazone, and troglitazone are PPAR agonists with demonstrable antiproliferative, and anti-inflammatory effects, in vivo, were shown to ameliorate PDR and CNV in rodent models, implying the potential efficacy of TZDs for treating proliferative retinopathies in humans. Activation of the angiotensin II type 1 receptor (AT1-R propagates proinflammatory and proliferative pathogenic determinants underlying PDR and CNV. The antihypertensive dual AT1-R blocker (ARB, telmisartan, recently was shown to activate PPAR and improve glucose and lipid metabolism and to clinically improve PDR and CNV in rodent models. Therefore, the TZDs and telmisartan, clinically approved antidiabetic and antihypertensive drugs, respectively, may be efficacious for treating and attenuating PDR and CNV humans. Clinical trials are needed to test these possibilities.

  9. Neovascular glaucoma in a child: an unusual presentation of medulloepithelioma

    Directory of Open Access Journals (Sweden)

    Kassa, Enoch

    2014-04-01

    Full Text Available [english] A healthy 12 month old infant without significant medical history presented with left eye redness for one week. Ophthalmic examination showed elevated intraocular pressure with iris neovascularization in the affected eye with increased optic nerve cupping. Scleral depression revealed a ciliary body mass in the supratemporal quadrant. A large, non-pigmented, vascular mass was noted; biopsy results showed multilayered cords, tubules, and sheets resembling primitive medullary epithelium arising from the ciliary body. The patient was diagnosed with medulloepithelioma. The patient underwent enucleation of the affected eye. Medulloepithelioma is a rare but important cause of neovascular glaucoma in the pediatric population. This case will focus on the characteristics of medulloepthelioma and the differential diagnosis for a non-pigmented ciliary body mass in a child.

  10. Leber congenital amaurosis associated with optic disk neovascularization and vitreous hemorrhage.

    Science.gov (United States)

    Kurz, Daryl; Ciulla, Thomas A

    2003-05-01

    To report an unusual case of optic disk neovascularization and vitreous hemorrhage associated with Leber congenital amaurosis (LCA). Interventional case report. A 16-year-old Caucasian girl with a history of LCA presented with decreased vision in her left eye, diffuse retinal pigmentary abnormalities characteristic of LCA, and hemorrhage over the left optic disk and macula. Six months of follow-up revealed optic disk neovascularization. A small amount of neovascularization was noted in the right eye at 6 months. An extensive systemic evaluation indicated no other cause for the neovascularization. Panretinal photocoagulation was performed in both eyes, and subsequently the neovascularization regressed. Leber congenital amaurosis like retinitis pigmentosa, can rarely be associated with neovascularization of the disk, which is amenable to treatment with peripheral photocoagulation if it does not spontaneously regress.

  11. Trabeculectomy versus Ahmed Glaucoma Valve implantation in neovascular glaucoma

    OpenAIRE

    Netland, Peter; Shen,Chris; Salim,Sarwat; Du,Haiming

    2011-01-01

    Christopher C Shen1, Sarwat Salim2, Haiming Du2, Peter A Netland31Glaucoma Consultants Northwest, Seattle, WA, USA; 2University of Tennessee Health Science Center, Memphis, TN, USA; 3University of Virginia School of Medicine, Charlottesville, VA, USAPurpose: To compare surgical outcomes in neovascular glaucoma patients who underwent trabeculectomy with mitomycin C versus Ahmed Glaucoma Valve implantation. Patients and methods: This was a retrospective comparative case series. We reviewed 40 e...

  12. Treatment of Corneal Neovascularization Using Anti-VEGF Bevacizumab

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    Deli Krizova

    2014-01-01

    Full Text Available Purpose. To evaluate antiangiogenic effect of local use of bevacizumab (anti-VEGF antibody in patients with corneal neovascularization. Methods. Patients were divided into two groups. All patients suffered from some form of corneal neovascularization (NV. Patients in group A received 0.2–0.5 mL of bevacizumab solution subconjunctivally (concentration 25 mg/mL in a single dose. Group A included 28 eyes from 27. Patients in group B applied bevacizumab eye drops twice daily (concentration 2.5 mg/mL for two weeks. Group B included 38 eyes from 35 patients. We evaluated the number of corneal segments affected by NV, CDVA, and the incidence of complications and subjective complaints related to the treatment. The minimum follow-up period was six months. Results. By the 6-month follow-up, in group A the percentage reduction of the affected peripheral segments was 21.6% and of the central segments was 9.6%; in group B the percentage reduction of the central segments was 22.7% and of the central segments was 38.04%. In both groups we noticed a statistically significant reduction in the extent of NV. Conclusion. The use of bevacizumab seems to be an effective and safe method in the treatment of corneal neovascularization, either in the subconjunctival or topical application form.

  13. Topical Ranibizumab as a Treatment of Corneal Neovascularization

    Science.gov (United States)

    Ferrari, Giulio; Dastjerdi, Mohammad H.; Okanobo, Andre; Cheng, Sheng-Fu; Amparo, Francisco; Nallasamy, Nambi; Dana, Reza

    2014-01-01

    Purpose To examine the effect of topical ranibizumab on clinically stable corneal neovascularization (NV). Methods This was a prospective, open-label, monocentric, uncontrolled, non-comparative study. Ten eyes of 9 patients with corneal NV received topical ranibizumab (1%) 4 times a day for 3 weeks with a follow-up of 16 weeks. The main corneal neovascularization outcome measures were: neovascular area (NA), the area occupied by the corneal neovessels; vessel caliber (VC), the mean diameter of the corneal neovessels; and invasion area (IA), the fraction of the total cornea area covered by the vessels. This study was conducted at the Massachusetts Eye and Ear Infirmary, Boston, MA, USA. Results Statistically significant decreases in NA (55.3%, P<0.001), which lasted through 16 weeks, and VC (59%, P<0.001), which continued to improve up to week 16, were observed after treatment. No significant decrease was observed in IA (12.3%, P=0.49). There was no statistically significant change in visual acuity or intraocular pressure. No adverse events ascribed to the treatment were noted. Conclusions Topical application of ranibizumab is effective in reducing the severity of corneal NV in the context of established corneal NV, mostly through decrease in VC rather than IA. PMID:23407316

  14. Trabeculectomy versus Ahmed Glaucoma Valve implantation in neovascular glaucoma

    Science.gov (United States)

    Shen, Christopher C; Salim, Sarwat; Du, Haiming; Netland, Peter A

    2011-01-01

    Purpose: To compare surgical outcomes in neovascular glaucoma patients who underwent trabeculectomy with mitomycin C versus Ahmed Glaucoma Valve implantation. Patients and methods: This was a retrospective comparative case series. We reviewed 40 eyes of 39 patients with underlying diagnosis of neovascular glaucoma, divided into two groups: Ahmed Glaucoma Valve (N = 20) and trabeculectomy with mitomycin C (N = 20). Surgical success was defined as 6 mm Hg ≤ intraocular pressure ≤21 mm Hg, with or without the use of glaucoma medications, with no further glaucoma surgery, and light perception or better vision. Early postoperative hypotony was defined as intraocular pressure Ahmed Glaucoma Valve group and 25 months (6–77 months) for the trabeculectomy group. Although the mean number of postoperative intraocular pressure-lowering medications was significantly higher in the trabeculectomy group compared with the Ahmed Glaucoma Valve group at 3 and 6 month time points, there was no statistically significant difference at any other time point. There was no statistically significant difference between both groups in postoperative visual acuity and intraocular pressure. Success was 70% and 65% at 1 year and 60% and 55% at 2 years after Ahmed Glaucoma Valve and trabeculectomy, respectively. Kaplan–Meier survival curve analysis showed no significant difference in success between the two groups (P = 0.815). Hyphema was the most common complication in both groups. Conclusion: We found similar results after trabeculectomy with mitomycin C and Ahmed Glaucoma Valve implantation in eyes with neovascular glaucoma. PMID:21468334

  15. Effect of Ahmed valve implantation on late neovascular glaucoma

    Directory of Open Access Journals (Sweden)

    Ping-An Mao

    2013-09-01

    Full Text Available AIM: To discuss the effect and safety of Ahmed valve implantation in late neovascular glaucoma. METHODS: The Ahmed glaucoma valve were implanted in 41 eyes(41 caseswith late neovascular glaucoma, the follow-up was 12 months on average, intraocular pressure was recorded at 1 day, 1 week, 1 month, 3, 6, 12 months respectively after operation and compared with that before operation, at the same time, the complications and treatment were analyzed.RESULTS: The mean intraocular pressure before operation, 1 day, 1 week, 1 month, 3, 6, 12 months after operation was 59.83±5.53, 19.27±8.19, 19.69±6.86, 20.67±6.73, 21.05±6.93, 21.49±7.42, 22.14±8.08mmHg, the mean intraocular pressure before operation was higher than that after operation and the difference was obvious in statistics. Major complications included hyphema, low intraocular pressure early postoperation, shallow anterior chamber, obstruction of the tube, the plate wrapped or exposed.CONCLUSION: Ahmed valve implantation is an effective method to treatlate neovascular glaucoma.

  16. Automated detection of neovascularization for proliferative diabetic retinopathy screening.

    Science.gov (United States)

    Roychowdhury, Sohini; Koozekanani, Dara D; Parhi, Keshab K

    2016-08-01

    Neovascularization is the primary manifestation of proliferative diabetic retinopathy (PDR) that can lead to acquired blindness. This paper presents a novel method that classifies neovascularizations in the 1-optic disc (OD) diameter region (NVD) and elsewhere (NVE) separately to achieve low false positive rates of neovascularization classification. First, the OD region and blood vessels are extracted. Next, the major blood vessel segments in the 1-OD diameter region are classified for NVD, and minor blood vessel segments elsewhere are classified for NVE. For NVD and NVE classifications, optimal region-based feature sets of 10 and 6 features, respectively, are used. The proposed method achieves classification sensitivity, specificity and accuracy for NVD and NVE of 74%, 98.2%, 87.6%, and 61%, 97.5%, 92.1%, respectively. Also, the proposed method achieves 86.4% sensitivity and 76% specificity for screening images with PDR from public and local data sets. Thus, the proposed NVD and NVE detection methods can play a key role in automated screening and prioritization of patients with diabetic retinopathy.

  17. Mesenchymal progenitor cells for the osteogenic lineage.

    Science.gov (United States)

    Ono, Noriaki; Kronenberg, Henry M

    2015-09-01

    Mesenchymal progenitors of the osteogenic lineage provide the flexibility for bone to grow, maintain its function and homeostasis. Traditionally, colony-forming-unit fibroblasts (CFU-Fs) have been regarded as surrogates for mesenchymal progenitors; however, this definition cannot address the function of these progenitors in their native setting. Transgenic murine models including lineage-tracing technologies based on the cre-lox system have proven to be useful in delineating mesenchymal progenitors in their native environment. Although heterogeneity of cell populations of interest marked by a promoter-based approach complicates overall interpretation, an emerging complexity of mesenchymal progenitors has been revealed. Current literatures suggest two distinct types of bone progenitor cells; growth-associated mesenchymal progenitors contribute to explosive growth of bone in early life, whereas bone marrow mesenchymal progenitors contribute to the much slower remodeling process and response to injury that occurs mainly in adulthood. More detailed relationships of these progenitors need to be studied through further experimentation.

  18. Enhanced adhesion of early endothelial progenitor cells to radiation-induced senescence-like vascular endothelial cells in vitro

    International Nuclear Information System (INIS)

    Sermsathanasawadi, N.; Inoue, Yoshinori; Iwai, Takehisa; Ishii, Hideto; Yoshida, Masayuki; Igarashi, Kaori; Miura, Masahiko

    2009-01-01

    The effects of ionizing radiation (IR) on tumor neovascularization are still unclear. We previously reported that vascular endothelial cells (ECs) expressing the IR-induced senescence-like (IRSL) phenotype exhibit a significant decrease in angiogenic activity in vitro. In this study, we examined the effects of the IRSL phenotype on adhesion to early endothelial progenitor cells (early EPCs). Adhesion of human peripheral blood-derived early EPCs to human umbilical vein endothelial cells (HUVECs) expressing the IRSL phenotype was evaluated by an adhesion assay under static conditions. It was revealed that the IRSL HUVECs supported significantly more adhesion of early EPCs than normal HUVECs. Expressions of ICAM-1, VCAM-1 and E-selectin were up-regulated in IRSL HUVECs. Pre-treatment of IRSL HUVECs with adhesion-blocking monoclonal antibodies against E-selectin and VCAM-1 significantly reduced early EPC adhesion to IRSL HUVECs, suggesting a potential role for the E-selectin and VCAM-1 in the adhesion between IRSL ECs and early EPCs. Therefore, the IRSL phenotype expressed in ECs may enhance neovascularization via increased homing of early EPCs. Our findings are first to implicate the complex effects of this phenotype on tumor neovascularization following irradiation. (author)

  19. Endothelial progenitor cells regenerate infracted myocardium with neovascularisation development.

    Science.gov (United States)

    Abd El Aziz, M T; Abd El Nabi, E A; Abd El Hamid, M; Sabry, D; Atta, H M; Rahed, L A; Shamaa, A; Mahfouz, S; Taha, F M; Elrefaay, S; Gharib, D M; Elsetohy, Khaled A

    2015-03-01

    We achieved possibility of isolation, characterization human umbilical cord blood endothelial progenitor cells (EPCs), examination potency of EPCs to form new blood vessels and differentiation into cardiomyoctes in canines with acute myocardial infarction (AMI). EPCs were separated and cultured from umbilical cord blood. Their phenotypes were confirmed by uptake of double stains dioctadecyl tetramethylindocarbocyanine-labeled acetylated LDL and FITC-labeled Ulex europaeus agglutinin 1 (DILDL-UEA-1). EPCs of cord blood were counted. Human VEGFR-2 and eNOS from the cultured EPCs were assessed by qPCR. Human EPCs was transplanted intramyocardially in canines with AMI. ECG and cardiac enzymes (CK-MB and Troponin I) were measured to assess severity of cellular damage. Histopathology was done to assess neovascularisation. Immunostaining was done to detect EPCs transdifferentiation into cardiomyocytes in peri-infarct cardiac tissue. qPCR for human genes (hVEGFR-2, and eNOS) was done to assess homing and angiogenic function of transplanted EPCs. Cultured human cord blood exhibited an increased number of EPCs and significant high expression of hVEGFR-2 and eNOS genes in the culture cells. Histopathology showed increased neovascularization and immunostaining showed presence of EPCs newly differentiated into cardiomyocyte-like cells. Our findings suggested that hEPCs can mediate angiogenesis and differentiate into cardiomyoctes in canines with AMI.

  20. Endothelial progenitor cells regenerate infracted myocardium with neovascularisation development

    Directory of Open Access Journals (Sweden)

    M.T. Abd El Aziz

    2015-03-01

    Full Text Available We achieved possibility of isolation, characterization human umbilical cord blood endothelial progenitor cells (EPCs, examination potency of EPCs to form new blood vessels and differentiation into cardiomyoctes in canines with acute myocardial infarction (AMI. EPCs were separated and cultured from umbilical cord blood. Their phenotypes were confirmed by uptake of double stains dioctadecyl tetramethylindocarbocyanine-labeled acetylated LDL and FITC-labeled Ulex europaeus agglutinin 1 (DILDL-UEA-1. EPCs of cord blood were counted. Human VEGFR-2 and eNOS from the cultured EPCs were assessed by qPCR. Human EPCs was transplanted intramyocardially in canines with AMI. ECG and cardiac enzymes (CK-MB and Troponin I were measured to assess severity of cellular damage. Histopathology was done to assess neovascularisation. Immunostaining was done to detect EPCs transdifferentiation into cardiomyocytes in peri-infarct cardiac tissue. qPCR for human genes (hVEGFR-2, and eNOS was done to assess homing and angiogenic function of transplanted EPCs. Cultured human cord blood exhibited an increased number of EPCs and significant high expression of hVEGFR-2 and eNOS genes in the culture cells. Histopathology showed increased neovascularization and immunostaining showed presence of EPCs newly differentiated into cardiomyocyte-like cells. Our findings suggested that hEPCs can mediate angiogenesis and differentiate into cardiomyoctes in canines with AMI.

  1. Correlation between clinical and histological features in a pig model of choroidal neovascularization

    DEFF Research Database (Denmark)

    Lassota, Nathan; Kiilgaard, Jens Folke; Prause, Jan Ulrik

    2006-01-01

    To analyse the histological changes in the retina and the choroid in a pig model of choroidal neovascularization (CNV) and to correlate these findings with fundus photographic and fluorescein angiographic features.......To analyse the histological changes in the retina and the choroid in a pig model of choroidal neovascularization (CNV) and to correlate these findings with fundus photographic and fluorescein angiographic features....

  2. Subfoveal fibrosis in eyes with neovascular age-related macular degeneration treated with intravitreal ranibizumab

    DEFF Research Database (Denmark)

    Bloch, Sara Brandi; Lund-Andersen, Henrik; Sander, Birgit

    2013-01-01

    To assess baseline and follow-up characteristics of choroidal neovascularization (CNV) lesions in age-related macular degeneration in relation to the development of subfoveal subretinal fibrosis.......To assess baseline and follow-up characteristics of choroidal neovascularization (CNV) lesions in age-related macular degeneration in relation to the development of subfoveal subretinal fibrosis....

  3. Verteporfin plus ranibizumab for choroidal neovascularization in age-related macular degeneration

    DEFF Research Database (Denmark)

    Larsen, Michael; Schmidt-Erfurth, Ursula; Lanzetta, Paolo

    2012-01-01

    To compare the efficacy and safety of same-day verteporfin photodynamic therapy (PDT) and intravitreal ranibizumab combination treatment versus ranibizumab monotherapy in neovascular age-related macular degeneration.......To compare the efficacy and safety of same-day verteporfin photodynamic therapy (PDT) and intravitreal ranibizumab combination treatment versus ranibizumab monotherapy in neovascular age-related macular degeneration....

  4. The association between Neovascular Age-related Macular Degeneration and Regulatory T cells in peripheral blood

    DEFF Research Database (Denmark)

    Madelung, Christopher Fugl; Falk, Mads; Sørensen, Torben Lykke

    2015-01-01

    PURPOSE: To investigate regulatory T cells (Tregs) and subsets of the Treg population in patients with neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: Twenty-one neovascular AMD cases and 12 age-matched controls without retinal pathology were selected. Patients were...

  5. Monozygotic twins with CAPN5 autosomal dominant neovascular inflammatory vitreoretinopathy

    Directory of Open Access Journals (Sweden)

    Rowell HA

    2012-12-01

    Full Text Available Hannah A Rowell,1,2 Alexander G Bassuk,3,4 Vinit B Mahajan1,21Omics Laboratory, 2Department of Ophthalmology and Visual Sciences, 3Department of Pediatrics, 4Department of Neurology, University of Iowa, Iowa City, IA, USABackground: The purpose of this study was to describe the clinical findings in a set of monozygotic twins with autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV over a 23-year period.Methods: A pair of female twins were examined between 26 and 49 years of age. The concordance and discordance of their clinical features were determined. The CAPN5 gene was sequenced using genomic DNA.Results: Both twins of an affected father demonstrated Stage I ADNIV with mild vitreous cells and a negative b-wave on electroretinography. Genetic analysis confirmed a guanine to thymine nucleotide (c.728G>T, pArg243Leu mutation in the CAPN5 gene. Over the course of 23 years, each twin progressed to stage III disease, showing posterior uveitis, cystoid macular edema, intraocular fibrosis, early retinal neovascularization, retinal degeneration, and cataract. Disease progression varied moderately between each twin and was asymmetrical between eyes. Twin A had 20/70 and 20/125 in the right and left eye, respectively, and underwent vitrectomy surgery and intravitreal injections with bevacizumab for recurrent cystoid macular edema. Twin B maintained 20/20 and 20/40 in the right and left eye, respectively without intervention.Conclusion: There was asymmetry between the eyes and some discordance in the rate of disease progression in these monozygotic twins with ADNIV. The overall high disease concordance suggests genetic factors play a major role in clinical manifestations in CAPN5 vitreoretinopathy.Keywords: autosomal dominant neovascular inflammatory vitreoretinopathy, ADNIV, CAPN5, calpain-5, monozygotic twins

  6. Desferrioxamine: a practical method for improving neovascularization of prefabricated flaps.

    Science.gov (United States)

    Li, Bin; Li, Hua; Jin, Rui; Cheng, Chen; Wang, Jing; Zhu, Hainan; Zan, Tao; Li, Qingfeng; Hao, Lijun

    2015-02-01

    Prefabricated flaps are an ideal alternative to repair massive and complex tissue defects. Nevertheless, the risk of necrosis due to unpredictable blood supplies is a major obstacle to the application of prefabricated flaps. The survival of a prefabricated flap depends on the neovascularization between the vascular carrier and the donor tissue. Here, we proposed that the iron chelator, desferrioxamine (DFX), owned therapeutic effects that promoted the neovascularization of prefabricated flaps. An abdominal prefabricated flap model was created in rats via a 2-stage operation. The rats were allocated into 4 groups as follows: 2 groups of rats received DFX treatments during the first or the second stage of the operation, respectively; 1 group of rats received a delay procedure 1 week before the second operation; and the final group was used as a blank control. Flap survival rates and capillary densities were evaluated between groups. The influence of DFX on the dermal fibroblasts was also studied in vitro. Desferrioxamine treatment during the first stage of the operation greatly increased flap survival rate compared to the blank control. The results were similar to those produced by the delay treatment. The vessel count results were consistent with the flap survival rate findings. In vitro, DFX treatment up-regulated the expression levels of several angiogenic factors in the dermal fibroblasts. Nevertheless, DFX treatment during the second stage of the operation was therapeutically detrimental. The application of DFX around the time of vascular carrier implantation greatly promoted neovascularization of prefabricated flaps, but was therapeutically detrimental after the flaps had been elevated.

  7. PATTERNS OF FUNDUS AUTOFLUORESCENCE DEFECTS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION SUBTYPES.

    Science.gov (United States)

    Ozkok, Ahmet; Sigford, Douglas K; Tezel, Tongalp H

    2016-11-01

    To test define characteristic fundus autofluorescence patterns of different exudative age-related macular degeneration subtypes. Cross-sectional study. Fifty-two patients with choroidal neovascularization because of three different neovascular age-related macular degeneration subtypes were included in the study. Macular and peripheral fundus autofluorescence patterns of study subjects were compared in a masked fashion. Fundus autofluorescence patterns of all three neovascular age-related macular degeneration subtypes revealed similar patterns. However, peripapillary hypo-autofluorescence was more common among patients with polypoidal choroidal vasculopathy (88.2%) compared with patients with retinal angiomatous proliferation (12.5%) and patients without retinal angiomatous proliferation and polypoidal choroidal vasculopathy (21.1%) (P autofluorescence defects in neovascular age-related macular degeneration maybe suggestive of polypoidal choroidal vasculopathy as a variant of neovascular age-related macular degeneration.

  8. Nanotechnology in corneal neovascularization therapy--a review.

    Science.gov (United States)

    Gonzalez, Lilian; Loza, Raymond J; Han, Kyu-Yeon; Sunoqrot, Suhair; Cunningham, Christy; Purta, Patryk; Drake, James; Jain, Sandeep; Hong, Seungpyo; Chang, Jin-Hong

    2013-03-01

    Nanotechnology is an up-and-coming branch of science that studies and designs materials with at least one dimension sized from 1-100 nm. These nanomaterials have unique functions at the cellular, atomic, and molecular levels. The term "nanotechnology" was first coined in 1974. Since then, it has evolved dramatically and now consists of distinct and independent scientific fields. Nanotechnology is a highly studied topic of interest, as nanoparticles can be applied to various fields ranging from medicine and pharmacology, to chemistry and agriculture, to environmental science and consumer goods. The rapidly evolving field of nanomedicine incorporates nanotechnology with medical applications, seeking to give rise to new diagnostic means, treatments, and tools. Over the past two decades, numerous studies that underscore the successful fusion of nanotechnology with novel medical applications have emerged. This has given rise to promising new therapies for a variety of diseases, especially cancer. It is becoming abundantly clear that nanotechnology has found a place in the medical field by providing new and more efficient ways to deliver treatment. Ophthalmology can also stand to benefit significantly from the advances in nanotechnology research. As it relates to the eye, research in the nanomedicine field has been particularly focused on developing various treatments to prevent and/or reduce corneal neovascularization among other ophthalmologic disorders. This review article aims to provide an overview of corneal neovascularization, currently available treatments, and where nanotechnology comes into play.

  9. Monozygotic twins with CAPN5 autosomal dominant neovascular inflammatory vitreoretinopathy.

    Science.gov (United States)

    Rowell, Hannah A; Bassuk, Alexander G; Mahajan, Vinit B

    2012-01-01

    The purpose of this study was to describe the clinical findings in a set of monozygotic twins with autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) over a 23-year period. A pair of female twins were examined between 26 and 49 years of age. The concordance and discordance of their clinical features were determined. The CAPN5 gene was sequenced using genomic DNA. Both twins of an affected father demonstrated Stage I ADNIV with mild vitreous cells and a negative b-wave on electroretinography. Genetic analysis confirmed a guanine to thymine nucleotide (c.728G>T, pArg243Leu) mutation in the CAPN5 gene. Over the course of 23 years, each twin progressed to stage III disease, showing posterior uveitis, cystoid macular edema, intraocular fibrosis, early retinal neovascularization, retinal degeneration, and cataract. Disease progression varied moderately between each twin and was asymmetrical between eyes. Twin A had 20/70 and 20/125 in the right and left eye, respectively, and underwent vitrectomy surgery and intravitreal injections with bevacizumab for recurrent cystoid macular edema. Twin B maintained 20/20 and 20/40 in the right and left eye, respectively without intervention. There was asymmetry between the eyes and some discordance in the rate of disease progression in these monozygotic twins with ADNIV. The overall high disease concordance suggests genetic factors play a major role in clinical manifestations in CAPN5 vitreoretinopathy.

  10. Nanotechnology in Corneal Neovascularization Therapy—A Review

    Science.gov (United States)

    Gonzalez, Lilian; Loza, Raymond J.; Han, Kyu-Yeon; Sunoqrot, Suhair; Cunningham, Christy; Purta, Patryk; Drake, James; Jain, Sandeep; Hong, Seungpyo

    2013-01-01

    Abstract Nanotechnology is an up-and-coming branch of science that studies and designs materials with at least one dimension sized from 1–100 nm. These nanomaterials have unique functions at the cellular, atomic, and molecular levels.1 The term “nanotechnology” was first coined in 1974.2 Since then, it has evolved dramatically and now consists of distinct and independent scientific fields. Nanotechnology is a highly studied topic of interest, as nanoparticles can be applied to various fields ranging from medicine and pharmacology, to chemistry and agriculture, to environmental science and consumer goods.3 The rapidly evolving field of nanomedicine incorporates nanotechnology with medical applications, seeking to give rise to new diagnostic means, treatments, and tools. Over the past two decades, numerous studies that underscore the successful fusion of nanotechnology with novel medical applications have emerged. This has given rise to promising new therapies for a variety of diseases, especially cancer. It is becoming abundantly clear that nanotechnology has found a place in the medical field by providing new and more efficient ways to deliver treatment. Ophthalmology can also stand to benefit significantly from the advances in nanotechnology research. As it relates to the eye, research in the nanomedicine field has been particularly focused on developing various treatments to prevent and/or reduce corneal neovascularization among other ophthalmologic disorders. This review article aims to provide an overview of corneal neovascularization, currently available treatments, and where nanotechnology comes into play. PMID:23425431

  11. Endothelial progenitor cells display clonal restriction in multiple myeloma

    International Nuclear Information System (INIS)

    Braunstein, Marc; Özçelik, Tayfun; Bağişlar, Sevgi; Vakil, Varsha; Smith, Eric LP; Dai, Kezhi; Akyerli, Cemaliye B; Batuman, Olcay A

    2006-01-01

    In multiple myeloma (MM), increased neoangiogenesis contributes to tumor growth and disease progression. Increased levels of endothelial progenitor cells (EPCs) contribute to neoangiogenesis in MM, and, importantly, covary with disease activity and response to treatment. In order to understand the mechanisms responsible for increased EPC levels and neoangiogenic function in MM, we investigated whether these cells were clonal by determining X-chromosome inactivation (XCI) patterns in female patients by a human androgen receptor assay (HUMARA). In addition, EPCs and bone marrow cells were studied for the presence of clonotypic immunoglobulin heavy-chain (IGH) gene rearrangement, which indicates clonality in B cells; thus, its presence in EPCs would indicate a close genetic link between tumor cells in MM and endothelial cells that provide tumor neovascularization. A total of twenty-three consecutive patients who had not received chemotherapy were studied. Screening in 18 patients found that 11 displayed allelic AR in peripheral blood mononuclear cells, and these patients were further studied for XCI patterns in EPCs and hair root cells by HUMARA. In 2 patients whose EPCs were clonal by HUMARA, and in an additional 5 new patients, EPCs were studied for IGH gene rearrangement using PCR with family-specific primers for IGH variable genes (V H ). In 11 patients, analysis of EPCs by HUMARA revealed significant skewing (≥ 77% expression of a single allele) in 64% (n = 7). In 4 of these patients, XCI skewing was extreme (≥ 90% expression of a single allele). In contrast, XCI in hair root cells was random. Furthermore, PCR amplification with V H primers resulted in amplification of the same product in EPCs and bone marrow cells in 71% (n = 5) of 7 patients, while no IGH rearrangement was found in EPCs from healthy controls. In addition, in patients with XCI skewing in EPCs, advanced age was associated with poorer clinical status, unlike patients whose EPCs had random XCI

  12. The poster as modernist progenitor

    Directory of Open Access Journals (Sweden)

    Katherine Hauser

    2015-12-01

    Full Text Available Ruth E. Iskin’s The Poster: Art, Advertising. Design, and Collecting, 1860s-1900s positions the late-nineteenth-century advertising poster as the progenitor of valued modernist practices typically attached solely to photography and film. Modernist biases separating high art from mass culture account for scholars ignoring posters, however the poster ushered in an innovative reductive graphic style as well as pioneered the notion of multiple originals.

  13. PROGENITORS OF RECOMBINING SUPERNOVA REMNANTS

    Energy Technology Data Exchange (ETDEWEB)

    Moriya, Takashi J., E-mail: takashi.moriya@ipmu.jp [Kavli Institute for the Physics and Mathematics of the Universe, Todai Institutes for Advanced Study, University of Tokyo, Kashiwanoha 5-1-5, Kashiwa, Chiba 277-8583 (Japan)

    2012-05-01

    Usual supernova remnants have either ionizing plasma or plasma in collisional ionization equilibrium, i.e., the ionization temperature is lower than or equal to the electron temperature. However, the existence of recombining supernova remnants, i.e., supernova remnants with ionization temperature higher than the electron temperature, has been recently confirmed. One suggested way to have recombining plasma in a supernova remnant is to have a dense circumstellar medium at the time of the supernova explosion. If the circumstellar medium is dense enough, collisional ionization equilibrium can be established in the early stage of the evolution of the supernova remnant and subsequent adiabatic cooling, which occurs after the shock wave gets out of the dense circumstellar medium, makes the electron temperature lower than the ionization temperature. We study the circumstellar medium around several supernova progenitors and show which supernova progenitors can have a circumstellar medium dense enough to establish collisional ionization equilibrium soon after the explosion. We find that the circumstellar medium around red supergiants (especially massive ones) and the circumstellar medium dense enough to make Type IIn supernovae can establish collisional ionization equilibrium soon after the explosion and can evolve to become recombining supernova remnants. Wolf-Rayet stars and white dwarfs have the possibility to be recombining supernova remnants but the fraction is expected to be very small. As the occurrence rate of the explosions of red supergiants is much higher than that of Type IIn supernovae, the major progenitors of recombining supernova remnants are likely to be red supergiants.

  14. Secondary glaucoma in CAPN5-associated neovascular inflammatory vitreoretinopathy

    Directory of Open Access Journals (Sweden)

    Cham A

    2016-06-01

    Full Text Available Abdourahman Cham,1,2 Mayank Bansal,3 Himanshu K Banda,4 Young Kwon,1 Paul S Tlucek,1 Alexander G Bassuk,5 Stephen H Tsang,6,7 Warren M Sobol,8 James C Folk,1 Steven Yeh,4 Vinit B Mahajan1,2 1Department of Ophthalmology and Visual Sciences, 2Omics Laboratory, University of Iowa, Iowa City, IA, USA; 3Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India; 4Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, 5Department of Pediatrics, University of Iowa, Iowa City, IA, 6Barbara and Donald Jonas Laboratory of Stem Cells and Regenerative Medicine and Bernard and Shirlee Brown Glaucoma Laboratory, Department of Pathology and Cell Biology, Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, 7Edward S Harkness Eye Institute, New York-Presbyterian Hospital, New York, NY, 8Retina Physicians & Surgeons, Inc., Dayton, OH, USA Objective: The objective of this study was to review the treatment outcomes of patients with secondary glaucoma in cases of autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV, a hereditary autoimmune uveitis due to mutations in CAPN5. Patients and methods: A retrospective, observational case series was assembled from ADNIV patients with secondary glaucoma. The main outcome measures were intraocular pressure (IOP, visual acuity, use of antiglaucoma medications, ocular surgeries, and adverse outcomes. Perimetry and optic disk optical coherence tomography (OCT were also analyzed. Results: Nine eyes of five ADNIV patients with secondary glaucoma were reviewed. Each received a fluocinolone acetonide (FA implant for the management of posterior uveitis. Following implantation, no eyes developed neovascular glaucoma. Five eyes (in patients 1, 2, and 5 required Ahmed glaucoma valve surgery for the management of steroid-responsive glaucoma. Patient 2 also developed angle closure with iris bombe and underwent laser

  15. Minocycline inhibits alkali burn-induced corneal neovascularization in mice.

    Directory of Open Access Journals (Sweden)

    Ou Xiao

    Full Text Available The purpose of this study was to investigate the effects of minocycline on alkali burn-induced corneal neovascularization (CNV. A total of 105 mice treated with alkali burns were randomly divided into three groups to receive intraperitoneal injections of either phosphate buffered saline (PBS or minocycline twice a day (60 mg/kg or 30 mg/kg for 14 consecutive days. The area of CNV and corneal epithelial defects was measured on day 4, 7, 10, and14 after alkali burns. On day 14, a histopathological examination was performed to assess morphological change and the infiltration of polymorphonuclear neutrophils (PMNs. The mRNA expression levels of vascular endothelial growth factor (VEGF and its receptors (VEGFRs, basic fibroblast growth factor (bFGF, matrix metalloproteinases (MMPs, interleukin-1α, 1β, 6 (IL-1α, IL-1β, IL-6 were analyzed using real-time quantitative polymerase chain reaction. The expression of MMP-2 and MMP-9 proteins was determined by gelatin zymography. In addition, enzyme-linked immunosorbent assay was used to analyze the protein levels of VEGFR1, VEGFR2, IL-1β and IL-6. Minocycline at a dose of 60 mg/kg or 30 mg/kg significantly enhanced the recovery of the corneal epithelial defects more than PBS did. There were significant decreases of corneal neovascularization in the group of high-dosage minocycline compared with the control group at all checkpoints. On day 14, the infiltrated PMNs was reduced, and the mRNA expression of VEGFR1, VEGFR2, bFGF, IL-1β, IL-6, MMP-2, MMP-9, -13 as well as the protein expression of VEGFR2, MMP-2, -9, IL-1β, IL-6 in the corneas were down-regulated with the use of 60 mg/kg minocycline twice a day. Our results showed that the intraperitoneal injection of minocycline (60 mg/kg b.i.d. can significantly inhibit alkali burn-induced corneal neovascularization in mice, possibly by accelerating corneal wound healing and by reducing the production of angiogenic factors, inflammatory cytokines and MMPs.

  16. Ultrasonographic demonstration of intraneural neovascularization after penetrating nerve injury.

    Science.gov (United States)

    Arányi, Zsuzsanna; Csillik, Anita; Dévay, Katalin; Rosero, Maja

    2018-06-01

    Hypervascularization of nerves has been shown to be a pathological sign in some peripheral nerve disorders, but has not been investigated in nerve trauma. An observational cohort study was performed of the intraneural blood flow of 30 patients (34 nerves) with penetrating nerve injuries, before or after nerve reconstruction. All patients underwent electrophysiological assessment, and B-mode and color Doppler ultrasonography. Intraneural hypervascularization proximal to the site of injury was found in all nerves, which was typically marked and had a longitudinal extension of several centimeters. In 6 nerves, some blood flow was also present within the injury site or immediately distal to the injury. No correlation was found between the degree of vascularization and age, size of the scar / neuroma, or degree of reinnervation. Neovascularization of nerves proximal to injury sites appears to be an essential element of nerve regeneration after penetrating nerve injuries. Muscle Nerve 57: 994-999, 2018. © 2018 Wiley Periodicals, Inc.

  17. Surgical induction of choroidal neovascularization in a porcine model

    DEFF Research Database (Denmark)

    Lassota, Nathan; Kiilgaard, Jens Folke; Prause, Jan Ulrik

    2007-01-01

    PURPOSE: To develop a reproducible surgical technique for the induction of choroidal neovascularization (CNV) in the subretinal space of porcine eyes and to analyse the resulting CNV clinically and histologically. METHODS: Two different modifications of a surgical technique previously described...... were compared with the original method. In ten porcine eyes retinal pigment epithelial (RPE) cells were removed using a silicone tipped cannula, in ten porcine eyes Bruch's membrane was perforated once with a retinal perforator without prior RPE removal and in ten eyes RPE removal was followed...... by a single perforation of Bruch's membrane. Fifteen of the eyes, five from each group, were enucleated 30 minutes after surgery, while the remaining eyes were enucleated after 14 days. Prior to enucleation, at day 14, fundus photographs and fluorescein angiograms were obtained. Eyes were examined by light...

  18. Dye-enhanced diode laser photocoagulation of choroidal neovascularizations

    Science.gov (United States)

    Klingbeil, Ulrich; Puliafito, Carmen A.; McCarthy, Dan; Reichel, Elias; Olk, Joseph; Lesiecki, Michael L.

    1994-06-01

    Dye-enhanced diode laser photocoagulation, using the dye indocyanine green (ICG), has shown some potential in the treatment of choroidal neovascularizations (CNV). A diode laser system was developed and optimized to emit at the absorption maximum of ICG. In a clinical study at two retinal centers, more than 70 patients, the majority of which had age-related macular degeneration, were treated. Eighteen cases with ill-defined subfoveal CNV were followed an average of 11 months after laser treatment. The results show success in resolving the CNV with an average long-term preservation of visual function equal to or superior to data provided by the Macular Photocoagulation Study for confluent burns of low intensity applied to the CNV. Details of the technique and discussion of the controversies inherent in such a treatment strategy will be presented.

  19. Helicoid peripapillary chorioretinal degeneration complicated by choroidal neovascularization.

    Science.gov (United States)

    Triantafylla, Magdalini; Panos, Georgios D; Dardabounis, Doukas; Nanos, Panagiotis; Konstantinidis, Aristeidis

    2016-02-15

    Helicoid peripapillary chorioretinal degeneration (HPCD) is a hereditary disease of the fundus that is characterized by atrophic chorioretinal areas that appear early in life and expand gradually from the optic disc towards the macula and the periphery. We describe the case of an elderly man with a known diagnosis of HPCD who developed choroidal neovascular membrane (CNV) in both eyes during the course of the disease. The patient was treated with intravitreal injection of ranibizumab, to which he had excellent response. The CNV subsided with 2 injections in the right eye and 1 in the left. Two years after the initial diagnosis of CNV in the right eye, visual acuity was 5/10 OD and 9/10 OS. Helicoid peripapillary chorioretinal degeneration is rarely complicated by CNV as the fundus lacks the trigger factors that would sustain this process. Although rare, HPCD complicated by CNV can be seen bilaterally, but responds well to few ranibizumab injections.

  20. Radiation Therapy for Neovascular Age-related Macular Degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Kishan, Amar U. [Harvard Medical School, Boston, Massachusetts (United States); Modjtahedi, Bobeck S.; Morse, Lawrence S. [Department of Ophthalmology and Vision Sciences, University of California, Davis, Sacramento, California (United States); Lee, Percy, E-mail: percylee@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States)

    2013-03-01

    In the enormity of the public health burden imposed by age-related macular degeneration (ARMD), much effort has been directed toward identifying effective and efficient treatments. Currently, anti-vascular endothelial growth factor (VEGF) injections have demonstrated considerably efficacy in treating neovascular ARMD, but patients require frequent treatment to fully benefit. Here, we review the rationale and evidence for radiation therapy of ARMD. The results of early photon external beam radiation therapy are included to provide a framework for the sequential discussion of evidence for the usage of stereotactic radiation therapy, proton therapy, and brachytherapy. The evidence suggests that these 3 modern modalities can provide a dose-dependent benefit in the treatment of ARMD. Most importantly, preliminary data suggest that all 3 can be used in conjunction with anti-VEGF therapeutics, thereby reducing the frequency of anti-VEGF injections required to maintain visual acuity.

  1. Diospyros kaki Extract Inhibits Alkali Burn-Induced Corneal Neovascularization.

    Science.gov (United States)

    Yang, Sung Jae; Jo, Hyoung; Kim, Kyung-A; Ahn, Hong Ryul; Kang, Suk Woo; Jung, Sang Hoon

    2016-01-01

    The purpose of this study was to evaluate the effect of ethanol extract of Diospyros kaki (EEDK) leaves on corneal neovascularization (CoNV) in rats. One week after the alkali burns in the corneas, the CoNV area coverage in the CoNV-positive control group, 100 mg/kg EEDK group, and 200 mg/kg EEDK group was 43.3% ± 5.5%, 337.7% ± 2.5%, and 27.2% ± 4.3%, respectively. The areas of CoNV in the EEDK-treated groups were significantly different from those of the CoNV group. EEDK significantly attenuated the upregulation of vascular endothelial growth factor, fibroblast growth factor, interleukin-6, and matrix metalloproteinase-2 (MMP-2) protein levels. Orally administrated D. kaki inhibited CoNV development in rats.

  2. Knockdown of the placental growth factor gene inhibits laser induced choroidal neovascularization in a murine model.

    Science.gov (United States)

    Nourinia, Ramin; Soheili, Zahra-Soheila; Ahmadieh, Hamid; Akrami, Hassan; Rezaei Kanavi, Mozhgan; Samiei, Shahram

    2013-01-01

    To evaluate the effect of placental growth factor (PlGF) gene knockdown in a murine model of laser-induced choroidal neovascularization. Choroidal neovascularization was induced in the left eyes of 11 mice by infrared laser. Small interfering RNA (siRNA, 20 picomoles/10 μl) corresponding to PlGF mRNA was administered intravitreally by Hamilton syringe in all subjects. One month later, fluorescein angiography and histolologic examination were performed. No leakage was apparent in the 11 eyes treated with siRNA cognate to PlGF. The results of histological evaluation were consistent with angiographic findings showing absence of choroidal neovascularization. Knockdown of the PlGF gene can inhibit the growth of laser-induced choroidal neovascularization in mice.

  3. Knockdown of the Placental Growth Factor Gene Inhibits Laser Induced Choroidal Neovascularization in a Murine Model

    Directory of Open Access Journals (Sweden)

    Ramin Nourinia

    2013-01-01

    Full Text Available Purpose: To evaluate the effect of placental growth factor (PlGF gene knockdown in a murine model of laser-induced choroidal neovascularization. Methods: Choroidal neovascularization was induced in the left eyes of 11 mice by infrared laser. Small interfering RNA (siRNA, 20 picomoles/10 μl corresponding to PlGF mRNA was administered intravitreally by Hamilton syringe in all subjects. One month later, fluorescein angiography and histolologic examination were performed. Results: No leakage was apparent in the 11 eyes treated with siRNA cognate to PlGF. The results of histological evaluation were consistent with angiographic findings showing absence of choroidal neovascularization. Conclusion: Knockdown of the PlGF gene can inhibit the growth of laser-induced choroidal neovascularization in mice.

  4. Somatostatin receptor 2A expression in choroidal neovascularization secondary to age-related macular degeneration

    NARCIS (Netherlands)

    A.C. Lambooij (Antoinette); R.W.A.M. Kuijpers (Robert); E.G. van Lichtenauer-Kaligis; M. Kliffen (Mike); G.S. Baarsma (Seerp); P.M. van Hagen (Martin); C.M. Mooy (Cornelia)

    2000-01-01

    textabstractPURPOSE: The growth of ocular neovascularization is regulated by a balance between stimulating and inhibiting growth factors. Somatostatin affects angiogenesis by inhibiting the growth hormone-insulin-like growth factor axis and also has a direct

  5. Apelin enhances cardiac neovascularization after myocardial infarction by recruiting aplnr+ circulating cells

    NARCIS (Netherlands)

    Tempel, D.; de Boer, M.; van Deel, E.D.; Haasdijk, R.A.; Duncker, D.J.G.M.; Cheng, C.; Schulte-Merker, S.; Duckers, H.J.

    2012-01-01

    RATIONALE: Neovascularization stimulated by local or recruited stem cells after ischemia is a key process that salvages damaged tissue and shows similarities with embryonic vascularization. Apelin receptor (Aplnr) and its endogenous ligand apelin play an important role in cardiovascular development.

  6. Apelin Enhances Cardiac Neovascularization After Myocardial Infarction By Recruiting Aplnr+ Circulating Cells

    NARCIS (Netherlands)

    Tempel, D.; Boer, de M.; Deel, van E.D.; Haasdijk, A.; Duncker, D.J.; Cheng, C.; Schulte-Merker, S.; Duckers, H.J.

    2012-01-01

    Rationale: Neovascularization stimulated by local or recruited stem cells after ischemia is a key process that salvages damaged tissue and shows similarities with embryonic vascularization. Apelin receptor (Aplnr) and its endogenous ligand apelin play an important role in cardiovascular development.

  7. Cataract surgery in patients with neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Kessel, Line; Theil, Pernille Koefoed; Sørensen, Torben Lykke

    2016-01-01

    Purpose To examine the outcome after cataract surgery in patients with neovascular age-related macular degeneration (AMD) treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections in routine clinical practice. Methods We extracted information about patients recorded...

  8. A prospective comparative study on neovascular glaucoma and non-neovascular refractory glaucoma following Ahmed glaucoma valve implantation.

    Science.gov (United States)

    Li, Zheng; Zhou, Minwen; Wang, Wei; Huang, Wenbin; Chen, Shida; Li, Xingyi; Gao, Xinbo; Zhang, Xiulan

    2014-01-01

    Neovascular glaucoma is a refractory disease, and difficult to manage. The aim of this study was to evaluate the clinical outcomes of Ahmed glaucoma valve implantation (AGVI) in neovascular glaucoma (NVG) and non-NVG patients. This prospective, non-randomized study included 55 eyes of 55 patients with refractory glaucoma; 27 had NVG (NVG group) and 28 had non-NVG (non-NVG group). All of the patients underwent AGVI. The NVG group was adjunctively injected with intravitreal ranibizumab/bevacizumab (IVR/IVB) before AGVI. Intraocular pressure (IOP) was the primary outcome measure in this study. Surgical success rate, number of antiglaucoma medications used, best corrected visual acuity (BCVA), and postoperative complications were analyzed between the groups. All of the patients completed the study (follow-up of 12 months). Kaplan-Meier survival curve analysis indicated that the qualified success rates in the NVG and non-NVG groups at 12 months were 70.5% and 92.9%, respectively; this difference was significant (P = 0.036). The complete success rates in the NVG and non-NVG groups at 12 months were 66.7% and 89.3%, respectively (P = 0.049). Compared with preoperative examinations, the postoperative mean IOP and use of medications were significantly lower at all follow-up time points in both groups (all P glaucoma, but the success rate of surgery was related to the type of refractory glaucoma. The complete and qualified success rates of NVG patient adjunctive anti-vascular endothelial growth factor treatment are still lower than those of non-NVG patients.

  9. Peripapillary Choroidal Neovascularization Associated with Optic Nerve Head Drusen Treated with Anti-VEGF Agents

    Directory of Open Access Journals (Sweden)

    Norman A. Saffra

    2015-02-01

    Full Text Available Optic nerve head drusen can be associated with peripapillary choroidal neovascularization, in both the pediatric and adult population. These membranes can involve the macula, causing significant visual loss. Herein, we present a case that required treatment with an anti-VEGF agent. The patient failed to respond to the initial agent, but subsequently responded to a change of agent. Adult patients with macular degeneration involving peripapillary choroidal neovascularization associated with optic nerve head drusen may require individualized treatment plans.

  10. Retcam fluorescein gonioangiography: a new modality for early detection of angle neovascularization in diabetic retinopathy.

    Science.gov (United States)

    Azad, Rajvardhan; Arora, Tarun; Sihota, Ramanjit; Chandra, Parijat; Mahajan, Deepankur; Sain, Siddarth; Sharma, Yograj

    2013-10-01

    To evaluate the role of Retcam fluorescein gonioangiography in detecting neovascularization of the angle and correlate the same with gonioscopy in diabetic retinopathy. One hundred and fifty eyes of 150 patients (25 each of mild, moderate, severe, very severe nonproliferative diabetic retinopathy (NPDR) proliferative diabetic retinopathy (PDR); and PDR with high-risk characteristics) were recruited. They underwent complete ocular examination including applanation tonometry, gonioscopy, Retcam fluorescein gonioangiography, and fundus fluorescein angiography. Using Retcam fluorescein gonioangiography, of 150 eyes neovascularization of the angle was detected in 37 eyes (24.66%) compared with 22 eyes (14.66%) on gonioscopy (P = 0.04). Small newly formed vessels were evident only with Retcam fluorescein gonioangiography. In 10 of 50 patients (20%) with severe/very severe NPDR, angle neovascularization was appreciable on Retcam fluorescein angiography compared with 5 patients (10%) on gonioscopy. Similarly, 25 of 50 patients (50%) with PDR/PDR with high-risk characteristics had neovascularization of the angle on Retcam gonioangiography compared with 17 (34%) on gonioscopy. Retcam fluorescein gonioangiography is a novel technique for early detection of angle neovascularization in diabetic retinopathy and hence preventing progression to neovascular glaucoma. The objective nature of this test helps in precise decision making compared with gonioscopy for early intervention especially in cases of pre-PDR.

  11. Spontaneous Regression of Choroidal Neovascularization in a Patient with Pattern Dystrophy

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    Anastasios Anastasakis

    2016-01-01

    Full Text Available Purpose. To present a case of a patient with pattern dystrophy (PD associated choroidal neovascularization (CNV that resolved spontaneously without treatment. Methods. A 69-year-old male patient was referred to our unit, for evaluation of a recent visual loss (metamorphopsias in his left eye. Fundus examination, fundus autofluorescence imaging, and fluorescein angiography showed a choroidal neovascular membrane in his left eye. Since visual acuity was satisfactory the patient elected observation. Clinical examination and OCT testing were repeated at 6 and 12 months after presentation. Results. Visual acuity remained stable at the level of 0.9 (baseline BCVA during the follow-up period (12 months. Repeat OCT testing showed complete spontaneous regression of the choroidal neovascular membrane without evidence of intra- or subretinal fluid in both follow-up visits. Conclusions. Spontaneous regression of choroidal neovascularization can occur in patients with retinal dystrophies and associated choroidal neovascular membranes. The decision to treat or observe these patients relies strongly on the presenting visual acuity, since, in isolated instances, spontaneous resolution of choroidal neovascularization may occur.

  12. Slit2 signaling through Robo1 and Robo2 is required for retinal neovascularization

    Science.gov (United States)

    Rama, Nicolas; Dubrac, Alexandre; Mathivet, Thomas; Chárthaigh, Róisín-Ana Ní; Genet, Gael; Cristofaro, Brunella; Pibouin-Fragner, Laurence; Ma, Le; Eichmann, Anne; Chédotal, Alain

    2016-01-01

    Ocular neovascular diseases are a leading cause of blindness. Vascular endothelial growth factor (VEGF) blockade improves vision, but not all individuals respond to anti-VEGF treatment, making additional means to prevent neovascularization necessary. Slit-family proteins (Slits) are ligands of Roundabout (Robo) receptors that repel developing axons in the nervous system. Robo1 expression is altered in ocular neovascular diseases, and previous in vitro studies have reported both pro- and anti-angiogenic effects of Slits. However, genetic evidence supporting a role for Slits in ocular neovascularization is lacking. Here we generated conditional knockout mice deficient in various Slit and Robo proteins and found that Slit2 potently and selectively promoted angiogenesis via Robo1 and Robo2 in mouse postnatal retina and in a model of ocular neovascular disease. Mechanistically, Slit2 acting through Robo1 and Robo2 promoted the migration of endothelial cells. These receptors are required for both Slit2- and VEGF-induced Rac1 activation and lamellipodia formation. Thus, Slit2 blockade could potentially be used therapeutically to inhibit angiogenesis in individuals with ocular neovascular disease. PMID:25894826

  13. Progenitor's Signatures in Type Ia Supernova Remnants

    NARCIS (Netherlands)

    Chiotellis, A.; Kosenko, D.; Schure, K.M.; Vink, J.

    2013-01-01

    The remnants of Type Ia supernovae (SNe Ia) can provide important clues about their progenitor histories. We discuss two well-observed supernova remnants (SNRs) that are believed to have resulted from SNe Ia, and use various tools to shed light on the possible progenitor histories. We find that

  14. Transplanting oligodendrocyte progenitors into the adult CNS

    International Nuclear Information System (INIS)

    Franklin, R.J.M.; Blakemore, W.F.; Cambridge Univ.

    1997-01-01

    This review covers a number of aspects of the behaviour of oligodendrocyte progenitors following transplantation into the adult CNS. First, an account is given of the ability of transplanted oligodendrocyte progenitors, grown in tissue culture in the presence of PDGF and bFGF, to extensively remyelinate focal areas of persistent demyelination. Secondly, we describe how transplanted clonal cell lines of oligodendrocyte progenitors will differentiate in to astrocytes as will oligodendrocytes following transplantation into pathological environments in which both oligodendrocytes and astrocytes are absent, thereby manifesting the bipotentially demonstrable in vitro but not during development. Finally, a series of studies examining the migratory behaviour of transplanted oligodendrocyte progenitors (modelled using the oligodendrocyte progenitor cell line CG4) are described. (author)

  15. Multimodal imaging and diagnosis of myopic choroidal neovascularization in Caucasians

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    Milani P

    2016-09-01

    Full Text Available Paolo Milani,1 Amedeo Massacesi,1 Stefania Moschini,1 Marco Setaccioli,1 Ennio Bulone,1 Gemma Tremolada,1 Stefano Ciaccia,1 Elena Mantovani,1 Daniela Morale,2 Fulvio Bergamini1 1Ophthalmology Department, Istituto Auxologico, 2Institute of Mathematics, Universita’ degli Studi di Milano, Milan, Italy Purpose: To investigate myopic choroidal neovascularization (mCNV by fluorescein angio­graphy (FA, spectral-domain optical coherence tomography (SD-OCT, near-infrared (NIR reflectance, and autofluorescence (AF. Methods: This retrospective study included 65 eyes of 62 Caucasian patients with a mean age of 66.72 years (95% confidence interval [CI] 63–70 years and a mean refraction of -9.72 diopters (95% CI -8.74 to -10.70 diopters. Results: Most of the mCNV cases were foveal-juxtafoveal (60/65, 92.3%, with thickening of the corresponding retina (62/65, 95.3% and leakage on FA (44/65, 67.6%. No retinal fluid was detectable in 32 (49.2% eyes and there was no hemorrhage in 25 (38.4% eyes. Papillary chorio­retinal atrophy was evident in 58 (89.2%, a shadowing effect in 48 (73.8%, and an epiretinal membrane in 38 (58.4% eyes. If an area of macular chorioretinal atrophy was present, mCNV frequently developed adjacent to it and was hyperfluorescent rather than with leakage (P<0.001. In eyes with edema or hemorrhage, hyper-reflective foci were more frequent (P<0.005. NIR and AF features were indeterminable in 19 (29.2% and 27 (41.5% eyes, respectively. The predominant feature was black or grayish on NIR (34/65, 52.3% and patchy (hypo- and hyperfluorescence was observed on AF (25/65, 38.4%. FA and SD-OCT correctly detected mCNV in 49 (75.3% and 48 (73.8% eyes, respectively, whereas NIR and AF exhibited limited diagnostic sensitivity. Doubtful diagnosis was associated with hyperfluorescent mCNV (P<0.001, absence of retinal fluid and epiretinal membrane (P<0.05, and presence of macular chorioretinal atrophy (P<0.01. Conclusion: Tomographic, angiographic, AF

  16. Intravitreal ranibizumab as adjuvant treatment for neovascular glaucoma

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    Flavia Gazze Ticly

    2013-04-01

    Full Text Available The purpose of this study was to describe a prospective case series of 5 eyes treated with intravitreal ranibizumab injection for neovascular glaucoma (NVG. Five patients with clinically uncontrolled NVG secondary to proliferative diabetic retinopathy (4 patients and central retinal vein occlusion (1 patient, non-responsive to maximal tolerable medication and panretinal photocoagulation, received intravitreal ranibizumab injection (0.5 mg. Patients were seen at 1st, 3rd and 7th day after the ranibizumab injection and when it was necessary. Success was defined as intraocular pressure (IOP 21, despite maximal tolerable medication, underwent trabeculectomy with 0.5mg/ml mitomycin C (MMC for 1 minute. Failure was defined as IOP > 21 mmHg, phthisis bulbi, loss of light perception or additional glaucoma surgery. The primary outcome was 6-month IOP control. Mean IOP before the ranibizumab injection was 37 mmHg (7 mmHg SD. Two out of five eyes underwent only ranibizumab injection, having an IOP control after the procedure. Three patients were submitted to trabeculectomy with MMC on the 7th day after the injection. At 6-month follow-up, the mean IOP was 12mmHg (3 mmHg SD. All eyes showed regression of rubeosis iridis and IOP control. Visual acuity improved in 2 eyes worsened in 1 eye, and remained stable in 2 eyes. These data suggest that intravitreal ranibizumab injection may be a useful tool in the treatment of NVG.

  17. Overload and neovascularization of shoulder tendons in volleyball players

    Science.gov (United States)

    2012-01-01

    Background In overhead sports like volleyball, the onset of a rotator cuff tendinopathy due to functional overload is a common observation. An angiofibroblastic etiopathogenesis has been hypothesized, whereby a greater anaerobic metabolism occurs in critical zones of the tendon with a lower degree of vascularization; this would induce collagen and extracellular matrix degradation, that could then trigger a compensatory neovascularization response. We performed a clinical observational study of 80 elite volleyball players, monitoring the perfusion values of the supraspinatus tendons by oximetry. Results No statistically significant differences were found between the oximetry data and age, sex or years of sports activity, nor when comparing the right and left arm or the dominant and non-dominant arm. A statistically significant difference was found for the dominant arm values in relation to the competitive role, higher values being obtained in outside hitters (62.7%) than middle hitters (53.7%) (p = 0.01), opposite hitters (55.5%) (p = 0.02) and libero players (54.4%) (p = 0.008), whereas there were no differences in setters (56.2%) (p > 0.05). Conclusions The different tendon vascularization values found in players with different roles in the team may be attributed to a response to the specific biomechanical demands posed by the different overhead throwing roles. PMID:22853746

  18. Resveratrol Improves Tube Formation in AGE-Induced Late Endothelial Progenitor Cells by Suppressing Syndecan-4 Shedding

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    Han Wu

    2018-01-01

    Full Text Available Dysfunction of endothelial progenitor cells (EPCs contributes to cardiovascular complications in diabetes, and resveratrol has been shown to improve EPC functions. Syndecan-4 (Synd4, a cell surface heparin sulfate proteoglycan, has been shown to promote neovascularization. Thus, the present study was performed to determine whether resveratrol promoted angiogenesis of EPCs by regulating Synd4. Late EPCs were isolated from human peripheral blood and stimulated with AGEs. Western blot showed that AGEs induced Synd4 shedding in a dose- and time-dependent manner. AGE-induced Synd4 shedding was partly reversed by NAC or resveratrol, along with normalized ROS production. Overexpression of Synd4 or pretreatment of resveratrol reversed AGE-impaired tube formation of EPCs and regulated the Akt/eNOS pathway. Furthermore, resveratrol suppressed Synd4 shedding via the inhibition of oxidative stress and improved tube formation of late EPCs via the regulation of the Synd4/Akt/eNOS pathway.

  19. Implementation studies of ranibizumab for neovascular age-related macular degeneration.

    Science.gov (United States)

    Bloch, Sara Brandi

    2013-11-01

    The pathogenesis of AMD is associated with age changes plus pathological changes involving oxidative stress and an altered inflammatory response leading to injury of retinal pigment epithelial cells and the adjacent choroidea and photoreceptor cells. AMD is divided into early, intermediate and advanced AMD. The advanced form of AMD is further divided into non-neovascular AMD and neovascular AMD. The diagnosis of neovascular AMD is based on FA and clinical characteristics of the eyes. The CNV lesions are by their growth pattern divided into type 1 CNV lesions, which grow primarily beneath the RPE, and type 2 CNV lesions, which have penetrated the RPE and evolve within the subretinal space. The natural course of neovascular AMD leads to visual disability in a majority of cases within the first years after onset, primarily caused by the development of subfoveal fibrous tissue and atrophy of the RPE. The prognosis of visual acuity in neovascular AMD has been markedly improved by the introduction of an intravitreal administered VEGF inhibitor (ranibizumab) given on a monthly basis. Treatment with ranibizumab for neovascular AMD was introduced in Denmark in 2006 under a fully reimbursed national healthcare plan. Treatment with ranibizumab is given in a variable dosing regimen that varies from the monthly dosing regimen administered in the studies that led to the approval of ranibizumab for neovascular AMD in Europe. The main objectives of this PhD thesis were to evaluate and potentially improve treatment with ranibizumab in a variable OCT guided regimen for neovascular AMD. Another intension of this PhD thesis was to prepare the conditions for future research to further improve the visual prognosis in neovascular AMD treated with anti-VEGF agents. The first study revealed that vision was improved in eyes with active neovascular AMD treated for 1 year in a variable ranibizumab treatment regimen as compared to PDT and the natural course of the disease. We assumed by

  20. The prevalence of neovascularity in patients clinically diagnosed with rotator cuff tendinopathy

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    Raza Syed A

    2009-12-01

    Full Text Available Abstract Background Shoulder dysfunction is common and pathology of the rotator cuff tendons and subacromial bursa are considered to be a major cause of pain and morbidity. Although many hypotheses exist there is no definitive understanding as to the origin of the pain arising from these structures. Research investigations from other tendons have placed intra-tendinous neovascularity as a potential mechanism of pain production. The prevalence of neovascularity in patients with a clinical diagnosis of rotator cuff tendinopathy is unknown. As such the primary aim of this pilot study was to investigate if neovascularity could be identified and to determine the prevalence of neovascularity in the rotator cuff tendons and subacromial bursa in subjects with unilateral shoulder pain clinically assessed to be rotator cuff tendinopathy. The secondary aims were to investigate the association between the presence of neovascularity and pain, duration of symptoms, and, neovascularity and shoulder function. Methods Patients with a clinical diagnosis of unilateral rotator cuff tendinopathy referred for a routine diagnostic ultrasound (US scan in a major London teaching hospital formed the study population. At referral patients were provided with an information document. On the day of the scan (on average, at least one week later the patients agreeing to participate were taken through the consent process and underwent an additional clinical examination prior to undergoing a bilateral grey scale and colour Doppler US examination (symptomatic and asymptomatic shoulder using a Philips HDI 5000 Sono CT US machine. The ultrasound scans were performed by one of two radiologists who recorded their findings and the final assessment was made by a third radiologist blinded both to the clinical examination and the ultrasound examination. The findings of the radiologists who performed the scans and the blinded radiologist were compared and any disagreements were resolved

  1. Neovascular Glaucoma Induced by Peripheral Retinal Ischemia in Neurofibromatosis Type 1: Management and Imaging Features

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    Francesco Pichi

    2013-04-01

    Full Text Available Purpose: To report the case of a young patient affected by neurofibromatosis 1 (NF-1 with peripheral retinal ischemia-induced neovascular glaucoma and the peculiar spectral-domain optical coherence tomography (SD-OCT features. Material and Methods: A 13-year-old boy affected by NF-1, as diagnosed according to established criteria, was referred with a diagnosis of hypertensive uveitis in his left eye. He underwent a complete ophthalmic examination and comprehensive blood work with viral and immunological tests. The case was documented with fluorescein angiography (FA and SD-OCT. When the intraocular pressure (IOP of the left eye decreased and the cornea cleared, FA revealed retinal ischemia and leakage from pathologic retinal vessels. SD-OCT revealed foveal hypoplasia secondary to the complete absence of the retinal nerve fiber layer. Results: Peripheral retinal ischemia-induced neovascular glaucoma was diagnosed. The patient underwent Ahmed valve implantation to control his IOP, and subsequent retinal photocoagulation by argon laser and intravitreal bevacizumab injection were performed to control neovascularization. Discussion: Retinal ischemia in NF-1 might lead to neovascular glaucoma: lowering of the IOP with surgical implantation of an Ahmed valve, regression of neovascularization by argon laser panretinal photocoagulation and intravitreal injection of bevacizumab can be a helpful way to control such a complication.

  2. Evaluation of Corneal Neovascularization Using Optical Coherence Tomography Angiography in Patients With Limbal Stem Cell Deficiency.

    Science.gov (United States)

    Oie, Yoshinori; Nishida, Kohji

    2017-11-01

    Detection of the exact area of corneal neovascularization using slit-lamp photography is often difficult. Thus, we evaluated corneal neovascularization in patients with limbal stem cell deficiency using optical coherence tomography angiography (OCTA). Five patients with 5 eyes showing partial or total limbal stem cell deficiency were enrolled. Three eyes had severe corneal scarring. Five 6- × 6-mm images (frontal, upper, lower, nasal, and temporal) were obtained by OCTA. Slit-lamp photography was performed for all patients on the same day. OCTA has 2 advantages over slit-lamp photography for clear demonstration of corneal neovascularization. First, OCTA can show neovascularization in cases with severe corneal opacification. Second, OCTA can detect not only large vessels but also small vessels that cannot be seen by slit-lamp photography. OCTA is a powerful tool for objective evaluation of vascularization in the anterior and posterior segments of the eye. We have demonstrated that OCTA can visualize corneal neovascularization in patients with corneal diseases more clearly than slit-lamp photography.

  3. Anti-vascular endothelial growth factor for neovascular glaucoma.

    Science.gov (United States)

    Simha, Arathi; Braganza, Andrew; Abraham, Lekha; Samuel, Prasanna; Lindsley, Kristina

    2013-10-02

    Neovascular glaucoma (NVG) is a potentially blinding secondary glaucoma. It is caused by the formation of abnormal new blood vessels which prevent normal drainage of aqueous from the anterior segment of the eye. Anti-vascular endothelial growth factor (anti-VEGF) agents are specific inhibitors of the primary mediators of neovascularization. Studies have reported the effectiveness of anti-VEGFs for the control of intraocular pressure (IOP) in NVG. To compare the IOP lowering effects of intraocular anti-VEGF agents to no anti-VEGF treatment, as an adjunct to existing modalities for the treatment of NVG. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to January 2013), EMBASE (January 1980 to January 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov/) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 January 2013. We included randomized controlled trials (RCTs) and quasi-RCTs of people treated with anti-VEGF agents for NVG. Two authors independently assessed the search results for trials to be included in the review. Discrepancies were resolved by discussion with a third author. Since no trial met our inclusion criteria, no assessment of risk of bias or meta-analysis was undertaken. No RCTs were found that met the inclusion criteria for this review. Two RCTs of anti-VEGF agents for treating NVG were not included in the review due to the heterogeneity and uncontrolled assignment of adjunct treatments received by the

  4. Celastrol nanoparticles inhibit corneal neovascularization induced by suturing in rats

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    Li ZR

    2012-03-01

    Full Text Available Zhanrong Li1, Lin Yao1, Jingguo Li2, Wenxin Zhang1, Xianghua Wu1, Yi Liu1, Miaoli Lin1, Wenru Su1, Yongping Li1, Dan Liang11State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, 2School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of ChinaPurpose: Celastrol, a traditional Chinese medicine, is widely used in anti-inflammation and anti-angiogenesis research. However, the poor water solubility of celastrol restricts its further application. This paper aims to study the effect of celastrol nanoparticles (CNPs on corneal neovascularization (CNV and determine the possible mechanism.Methods: To improve the hydrophilicity of celastrol, celastrol-loaded poly(ethylene glycol-block-poly(ε-caprolactone nanopolymeric micelles were developed. The characterization of CNPs was measured by dynamic light scattering and transmission electron microscopy analysis. Celastrol loading content and release were assessed by ultraviolet-visible analysis and high performance liquid chromatography, respectively. In vitro, human umbilical vein endothelial cell proliferation and capillary-like tube formation were assayed. In vivo, suture-induced CNV was chosen to evaluate the effect of CNPs on CNV in rats. Immunohistochemistry for CD68 assessed the macrophage infiltration of the cornea on day 6 after surgery. Real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were used to evaluate the messenger ribonucleic acid and protein levels, respectively, of vascular endothelial growth factor, matrix metalloproteinase 9, and monocyte chemoattractant protein 1 in the cornea.Results: The mean diameter of CNPs with spherical shape was 48 nm. The celastrol loading content was 7.36%. The release behavior of CNPs in buffered solution (pH 7.4 showed a typical two-phase release profile. CNPs inhibited the proliferation of human umbilical vein endothelial

  5. Clinical observation of two operation methods for neovascular glaucoma

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    Peng Zhang

    2013-11-01

    Full Text Available AIM: To evaluate the clinical effect of two different surgical treatments for neovascular glaucoma(NVG.METHODS: A total of 30 NVG inpatients(30 eyesat our hospital from April 2008 to December 2011 were reviewed. Patients were divided into two groups according to the different surgical treatments. In group A, 12 cases(12 eyeswere treated with Ahmed glaucoma valve(AGVimplantation and in group B, 18 cases(18 eyeswere treated with semiconductor diode laser photocoagulation transscleral cyclophotocoagulation(TSCPC. Intraocular pressure, visual acuity and complications were compared between two groups postoperatively.RESULTS: The postoperative IOP was significantly lower in each group(PPP>0.05in IOP 1 month after surgery. Visual acuity: in group A, the visual acuity was improved in 3 eyes, unchanged in 7 eyes and worsened in 2 eyes.; in group B, the visual acuity was improved in 3 eyes, unchanged in 12 eyes and worsened in 3 eyes. Postoperative complications: in group A, eyeball pain and corneal edema were found in 5 cases(41.7%, shallow anterior chamber in 3 cases(25%, anterior chamber fibroid exudation in 2 cases(16.7%, hyphema in 3 cases(25%; in group B, eyeball pain atearly stage after surgery were found in 10 cases(55.6% , corneal edema in 11 cases(61.1%, anterior chamber fibroid exudation in 5 cases(27.8%, hyphema in 6 cases(33.3%.CONCLUSION: AGV implantation and TSCPC are both effective surgical treatment methods for NVG. AGV implantation is a filtration surgery, which is relatively safe. TSCPC is more economical and suitable for glaucoma of advanced or absolute stage.

  6. Placental Growth Factor Promotes Cardiac Muscle Repair via Enhanced Neovascularization

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    Jianfeng Zhang

    2015-06-01

    Full Text Available Background/Aims: Transplantation of mesenchymal stem cells (MSCs improves post-injury cardiac muscle repair using ill-defined mechanisms. Recently, we have shown that production and secretion of placental growth factor (PLGF by MSCs play a critical role in the MSCs-mediated post-injury cardiac muscle repair. In this study, we addressed the underlying molecular mechanisms, focusing specifically on the interactions between MSCs, macrophages and endothelial cells. Methods: We isolated macrophages (BM-MΦ from mouse bone-marrow derived cells based on F4/80 expression by flow cytometry. BM-MΦ were treated with different doses of PLGF. Cell number was analyzed by a MTT assay. Macrophage polarization was examined based on CD206 expression by flow cytometry. PLGF levels in macrophage subpopulations were analyzed by RT-qPCR and ELISA. Effects of macrophages on vascularization were evaluated by a collagen gel assay using Human umbilical vein endothelial cells (HUVECs co-cultured with PLGF-treated macrophages. Results: PLGF did not increase macrophage number, but dose-dependently polarized macrophages into a M2 subpopulation. M2 macrophages expressed high levels of PLGF. PLGF-polarized M2 macrophages significantly increased tubular structures in the collagen gel assay. Conclusion: Our data suggest that MSCs-derived PLGF may induce macrophage polarization into a M2 subpopulation, which in turn releases more PLGF to promote local neovascularization for augmenting post-injury cardiac muscle repair. This study thus sheds novel light on the role of PLGF in cardiac muscle regeneration.

  7. High levels of circulating VEGFR2+ Bone marrow-derived progenitor cells correlate with metastatic disease in patients with pediatric solid malignancies.

    Science.gov (United States)

    Taylor, Melissa; Rössler, Jochen; Geoerger, Birgit; Laplanche, Agnès; Hartmann, Olivier; Vassal, Gilles; Farace, Françoise

    2009-07-15

    Pediatric solid malignancies display important angiogenic potential, and blocking tumor angiogenesis represents a new therapeutic approach for these patients. Recent studies have evidenced rare circulating cells with endothelial features contributing to tumor neovascularization and have shown the pivotal role of bone marrow-derived (BMD) progenitor cells in metastatic disease progression. We measured these cells in patients with pediatric solid malignancies as a prerequisite to clinical trials with antiangiogenic therapy. Peripheral blood was drawn from 45 patients with localized (n = 23) or metastatic (n = 22) disease, and 20 healthy subjects. Subsets of circulating vascular endothelial growth factor receptor (VEGFR)2+-BMD progenitor cells, defined as CD45-CD34+VEGFR2(KDR)+7AAD- and CD45(dim)CD34+VEGFR2+7AAD- events, were measured in progenitor-enriched fractions by flow cytometry. Mature circulating endothelial cells (CEC) were measured in whole blood as CD31+CD146+CD45-7AAD- viable events. Data were correlated with VEGF and sVEGFR2 plasma levels. The CD45-CD34+VEGFR2(KDR)+7AAD- subset represented <0.003% of circulating BMD progenitor cells (< or =0.05 cells/mL). However, the median level (range) of the CD45(dim)CD34+VEGFR2+7AAD- subset was higher in patients compared with healthy subjects, 1.5% (0%-10.3%) versus 0.3% (0%-1.6%) of circulating BMD progenitors (P < 0.0001), and differed significantly between patients with localized and metastatic disease, 0.7% (0%-8.6%) versus 2.9% (0.6%-10.3%) of circulating BMD progenitors (P < 0.001). Median CEC value was 7 cells/mL (0-152 cells/mL) and similar in all groups. Unlike VEGFR2+-BMD progenitors, neither CECs, VEGF, or sVEGFR2 plasma levels correlated with disease status. High levels of circulating VEGFR2+-BMD progenitor cells correlated with metastatic disease. Our study provides novel insights for angiogenesis mechanisms in pediatric solid malignancies for which antiangiogenic targeting of VEGFR2+-BMD progenitors

  8. Progenitor cells in pulmonary vascular remodeling

    Science.gov (United States)

    Yeager, Michael E.; Frid, Maria G.; Stenmark, Kurt R.

    2011-01-01

    Pulmonary hypertension is characterized by cellular and structural changes in the walls of pulmonary arteries. Intimal thickening and fibrosis, medial hypertrophy and fibroproliferative changes in the adventitia are commonly observed, as is the extension of smooth muscle into the previously non-muscularized vessels. A majority of these changes are associated with the enhanced presence of α-SM-actin+ cells and inflammatory cells. Atypical abundances of functionally distinct endothelial cells, particularly in the intima (plexiform lesions), and also in the perivascular regions, are also described. At present, neither the origin(s) of these cells nor the molecular mechanisms responsible for their accumulation, in any of the three compartments of the vessel wall, have been fully elucidated. The possibility that they arise from either resident vascular progenitors or bone marrow–derived progenitor cells is now well established. Resident vascular progenitor cells have been demonstrated to exist within the vessel wall, and in response to certain stimuli, to expand and express myofibroblastic, endothelial or even hematopoietic markers. Bone marrow–derived or circulating progenitor cells have also been shown to be recruited to sites of vascular injury and to assume both endothelial and SM-like phenotypes. Here, we review the data supporting the contributory role of vascular progenitors (including endothelial progenitor cells, smooth muscle progenitor cells, pericytes, and fibrocytes) in vascular remodeling. A more complete understanding of the processes by which progenitor cells modulate pulmonary vascular remodeling will undoubtedly herald a renaissance of therapies extending beyond the control of vascular tonicity and reduction of pulmonary artery pressure. PMID:22034593

  9. Both Autocrine Signaling and Paracrine Signaling of HB-EGF Enhance Ocular Neovascularization.

    Science.gov (United States)

    Inoue, Yuki; Shimazawa, Masamitsu; Nakamura, Shinsuke; Takata, Shinsuke; Hashimoto, Yuhei; Izawa, Hiroshi; Masuda, Tomomi; Tsuruma, Kazuhiro; Sakaue, Tomohisa; Nakayama, Hironao; Higashiyama, Shigeki; Hara, Hideaki

    2018-01-01

    The incidence of blindness is increasing because of the increase in abnormal ocular neovascularization. Anti-VEGF (vascular endothelial growth factor) therapies have led to good results, although they are not a cure for the blindness. The purpose of this study was to determine what role HB-EGF (heparin-binding epidermal growth factor-like growth factor) plays in ocular angiogenesis. We examined the role played by HB-EGF in ocular neovascularization in 2 animal models of neovascularization: laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy. We also studied human retinal microvascular endothelial cells in culture. Our results showed that the neovascularization was decreased in both the CNV and oxygen-induced retinopathy models in HB-EGF conditional knockout mice compared with that in wild-type mice. Moreover, the expressions of HB-EGF and VEGF were increased after laser-induced CNV and oxygen-induced retinopathy, and their expression sites were located around the neovascular areas. Exposure of human retinal microvascular endothelial cells to HB-EGF and VEGF increased their proliferation and migration, and CRM-197 (cross-reactive material-197), an HB-EGF inhibitor, decreased the HB-EGF-induced and VEGF-induced cell proliferation and migration. VEGF increased the expression of HB-EGF mRNA. VEGF-dependent activation of EGFR (epidermal growth factor receptor)/ERK1/2 (extracellular signal-regulated kinase 1/2) signaling and cell proliferation of endothelial cells required stimulation of the ADAM17 (a disintegrin and metalloprotease) and ADAM12. CRM-197 decreased the grades of the fluorescein angiograms and size of the CNV areas in marmoset monkeys. These findings suggest that HB-EGF plays an important role in the development of CNV. Therefore, further investigations of HB-EGF are needed as a potential therapeutic target in the treatment of exudative age-related macular degeneration. © 2017 American Heart Association, Inc.

  10. Suppression of T cell-induced osteoclast formation

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    Karieb, Sahar; Fox, Simon W., E-mail: Simon.fox@plymouth.ac.uk

    2013-07-12

    Highlights: •Genistein and coumestrol prevent activated T cell induced osteoclast formation. •Anti-TNF neutralising antibodies prevent the pro-osteoclastic effect of activated T cells. •Phytoestrogens inhibit T cell derived TNF alpha and inflammatory cytokine production. •Phytoestrogens have a broader range of anti-osteoclastic actions than other anti-resorptives. -- Abstract: Inhibition of T cell derived cytokine production could help suppress osteoclast differentiation in inflammatory skeletal disorders. Bisphosphonates are typically prescribed to prevent inflammatory bone loss but are not tolerated by all patients and are associated with an increased risk of osteonecrosis of the jaw. In light of this other anti-resorptives such as phytoestrogens are being considered. However the effect of phytoestrogens on T cell-induced osteoclast formation is unclear. The effect of genistein and coumestrol on activated T cell-induced osteoclastogenesis and cytokine production was therefore examined. Concentrations of genistein and coumestrol (10{sup −7} M) previously shown to directly inhibit osteoclast formation also suppressed the formation of TRAP positive osteoclast induced by con A activated T cells, which was dependent on inhibition of T cell derived TNF-α. While both reduced osteoclast formation their mechanism of action differed. The anti-osteoclastic effect of coumestrol was associated with a dual effect on con A induced T cell proliferation and activation; 10{sup −7} M coumestrol significantly reducing T cell number (0.36) and TNF-α (0.47), IL-1β (0.23) and IL-6 (0.35) expression, whereas genistein (10{sup −7} M) had no effect on T cell number but a more pronounced effect on T cell differentiation reducing expression of TNF-α (0.49), IL-1β (0.52), IL-6 (0.71) and RANKL (0.71). Phytoestrogens therefore prevent the pro-osteoclastic action of T cells suggesting they may have a role in the control of inflammatory bone loss.

  11. THE GOAL OF VALUE-BASED MEDICINE ANALYSES: COMPARABILITY. THE CASE FOR NEOVASCULAR MACULAR DEGENERATION

    Science.gov (United States)

    Brown, Gary C.; Brown, Melissa M.; Brown, Heidi C.; Kindermann, Sylvia; Sharma, Sanjay

    2007-01-01

    Purpose To evaluate the comparability of articles in the peer-reviewed literature assessing the (1) patient value and (2) cost-utility (cost-effectiveness) associated with interventions for neovascular age-related macular degeneration (ARMD). Methods A search was performed in the National Library of Medicine database of 16 million peer-reviewed articles using the key words cost-utility, cost-effectiveness, value, verteporfin, pegaptanib, laser photocoagulation, ranibizumab, and therapy. All articles that used an outcome of quality-adjusted life-years (QALYs) were studied in regard to (1) percent improvement in quality of life, (2) utility methodology, (3) utility respondents, (4) types of costs included (eg, direct healthcare, direct nonhealthcare, indirect), (5) cost bases (eg, Medicare, National Health Service in the United Kingdom), and (6) study cost perspective (eg, government, societal, third-party insurer). To qualify as a value-based medicine analysis, the patient value had to be measured using the outcome of the QALYs conferred by respective interventions. As with value-based medicine analyses, patient-based time tradeoff utility analysis had to be utilized, patient utility respondents were necessary, and direct medical costs were used. Results Among 21 cost-utility analyses performed on interventions for neovascular macular degeneration, 15 (71%) met value-based medicine criteria. The 6 others (29%) were not comparable owing to (1) varying utility methodology, (2) varying utility respondents, (3) differing costs utilized, (4) differing cost bases, and (5) varying study perspectives. Among value-based medicine studies, laser photocoagulation confers a 4.4% value gain (improvement in quality of life) for the treatment of classic subfoveal choroidal neovascularization. Intravitreal pegaptanib confers a 5.9% value gain (improvement in quality of life) for classic, minimally classic, and occult subfoveal choroidal neovascularization, and photodynamic therapy

  12. Clinical correlates of common corneal neovascular diseases:a literature review

    Directory of Open Access Journals (Sweden)

    Nizar Saleh Abdelfattah

    2015-02-01

    Full Text Available A large subset of corneal pathologies involves the formation of new blood and lymph vessels (neovascularization, leading to compromised visual acuity. This article aims to review the clinical causes and presentations of corneal neovascularization (CNV by examining the mechanisms behind common CNV-related corneal pathologies, with a particular focus on herpes simplex stromal keratitis, contact lenses-induced keratitis and CNV secondary to keratoplasty. Moreover, we reviewed CNV in the context of different types of corneal transplantation and keratoprosthesis, and summarized the most relevant treatments available so far.

  13. Systemic diffuse large B-cell lymphoma masquerading as neovascular glaucoma.

    Science.gov (United States)

    Bawankar, Pritam; Das, Dipankar; Bhattacharjee, Harsha; Tayab, Shahinur; Deori, Nilutparna; Paulbuddhe, Vivek; Dhar, Shriya; Deka, Apurba

    2018-02-01

    We describe a case of spontaneous hyphema associated with anterior uveitis presents in a 69-year old female as the prominent sign of the intraocular spread of systemic diffuse large B-cell lymphoma (DLBCL). She had a history of diabetes and initially misdiagnosed as neovascular glaucoma. Clinical history of systemic lymphoma, characteristic findings on B-scan ultrasonography and magnetic resonance imaging scan, and identification of atypical lymphoid cells in aqueous sample established the diagnosis of intraocular metastasis of systemic DLBCL. Therefore, this report highlights that life-threatening malignant systemic lymphoma may masquerade as anterior segment ocular inflammation or neovascular glaucoma.

  14. The goal of value-based medicine analyses: comparability. The case for neovascular macular degeneration.

    Science.gov (United States)

    Brown, Gary C; Brown, Melissa M; Brown, Heidi C; Kindermann, Sylvia; Sharma, Sanjay

    2007-01-01

    To evaluate the comparability of articles in the peer-reviewed literature assessing the (1) patient value and (2) cost-utility (cost-effectiveness) associated with interventions for neovascular age-related macular degeneration (ARMD). A search was performed in the National Library of Medicine database of 16 million peer-reviewed articles using the key words cost-utility, cost-effectiveness, value, verteporfin, pegaptanib, laser photocoagulation, ranibizumab, and therapy. All articles that used an outcome of quality-adjusted life-years (QALYs) were studied in regard to (1) percent improvement in quality of life, (2) utility methodology, (3) utility respondents, (4) types of costs included (eg, direct healthcare, direct nonhealthcare, indirect), (5) cost bases (eg, Medicare, National Health Service in the United Kingdom), and (6) study cost perspective (eg, government, societal, third-party insurer). To qualify as a value-based medicine analysis, the patient value had to be measured using the outcome of the QALYs conferred by respective interventions. As with value-based medicine analyses, patient-based time tradeoff utility analysis had to be utilized, patient utility respondents were necessary, and direct medical costs were used. Among 21 cost-utility analyses performed on interventions for neovascular macular degeneration, 15 (71%) met value-based medicine criteria. The 6 others (29%) were not comparable owing to (1) varying utility methodology, (2) varying utility respondents, (3) differing costs utilized, (4) differing cost bases, and (5) varying study perspectives. Among value-based medicine studies, laser photocoagulation confers a 4.4% value gain (improvement in quality of life) for the treatment of classic subfoveal choroidal neovascularization. Intravitreal pegaptanib confers a 5.9% value gain (improvement in quality of life) for classic, minimally classic, and occult subfoveal choroidal neovascularization, and photodynamic therapy with verteporfin confers

  15. Radiation therapy for subfoveal chroidal neovascularization complicating age-related macular degeneration

    International Nuclear Information System (INIS)

    Kawabata, Yuko; Ohara, Masae; Ishii, Kentaro

    2004-01-01

    We evaluated the effect of low-dose external beam irradiation on the visual function of 14 eyes with subfoveal chroidal neovascularization complicating age-related macular degeneration. Patient received external beam irradiation at a dose of 20 Gy in 10 fraction of 2 Gy. After treatment the visual function improved in 2 eyes, remained stable in 8 eyes and deteriorated in 4 eyes. At the last examination visual function improved in 1 eyes, remained stable in 2 eyes and deteriorated in 5 eyes. The low-dose irradiation is potentially beneficial for subfoveal chroidal neovascularization complicating age-related macular degeneration. (author)

  16. Application of Ranibizumab at perioperative period of compound trabeculectomy in patients with neovascular glaucoma

    Directory of Open Access Journals (Sweden)

    Su-Ying Qin

    2016-01-01

    Full Text Available AIM:To observe the effect of intravitreal injection of Ranibizumab at perioperative period of compound trabeculectomy on iris neovascularization, intraocular pressure(IOPfor patients with neovascular glaucoma(NVG.METHODS:Intravitreal injection of ranibizumab, compound trabeculectomy and panretinal photocoagulation were given to 38 patients(38 eyeswith neovascular glaucoma, which could not be controlled by drugs, from January 2013 to January 2014 in Anyang Eye Hospital. Iris neovascularization, IOP and changes of visual acuity were observed before and after treatments. The patients were followed up for 6mo after treatments.RESULTS: Seven days after intravitreal injection, 36 cases(94.74%had complete regression of iris neovascularization. Two cases(5.26%had regression of small blood vessels in the iris, a little thick blood vessels were remained. At 1mo after compound trabeculectomy, iris neovascularization in all patients were subsided; at 3mo after treatments, the iris neovascularization in 8 patients(21.05%were performed again, and accepted intravitreal injection of ranibizumab again. Six months after the first treatments, all patients showed no iris neovascularization. The mean IOP before injection was 42.82±10.29mmHg. At 5d after the drug injection was 39.13±9.71mmHg. Before and after the drug injection, change of IOP was not statistically significant(q=2.65, P>0.05. At 1wk,1,3 and 6mo after compound trabeculectomy, IOP was 10.53±1.81mmHg, 10.11±1.73mmHg, 11.29±2.49mmHg, 12.58±3.01mmHg,which decreased significantly(q=23.15,23.46,22.61,21.68, all Pq=20.51,20.81,19.96,19.04, all PCONCLUSION: Intravitreal injection of ranibizumab at perioperative period of compound trabeculectomy can effectively improve the success rate of the surgeries and reduce risk of complications, and the effect is certainly safe.

  17. Multilayered pigment epithelial detachment in neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Rahimy, Ehsan; Freund, K Bailey; Larsen, Michael

    2014-01-01

    , hyperreflective bands, termed a "multilayered PED," which is often seen in conjunction with neovascular tissue adherent to the undersurface of the retinal pigment epithelium monolayer. On the basis of previous histopathologic correlations, these bands may represent a fibrous tissue complex with contractile...... properties. An associated hyporeflective space, termed a "pre-choroidal cleft," separates the fusiform complex from the underlying choroid and may be due to contraction, the exudation of fluid, or both. Many of these eyes maintain good visual acuity, presumably because the neovascular and cicatricial process...

  18. Interactions between endothelial progenitor cells (EPC) and titanium implant surfaces.

    Science.gov (United States)

    Ziebart, Thomas; Schnell, Anne; Walter, Christian; Kämmerer, Peer W; Pabst, Andreas; Lehmann, Karl M; Ziebart, Johanna; Klein, Marc O; Al-Nawas, Bilal

    2013-01-01

    Endothelial cells play an important role in peri-implant angiogenesis during early bone formation. Therefore, interactions between endothelial progenitor cells (EPCs) and titanium dental implant surfaces are of crucial interest. The aim of our in vitro study was to investigate the reactions of EPCs in contact with different commercially available implant surfaces. EPCs from buffy coats were isolated by Ficoll density gradient separation. After cell differentiation, EPC were cultured for a period of 7 days on different titanium surfaces. The test surfaces varied in roughness and hydrophilicity: acid-etched (A), sand-blasted-blasted and acid-etched (SLA), hydrophilic A (modA), and hydrophilic SLA (modSLA). Plastic and fibronectin-coated plastic surfaces served as controls. Cell numbers and morphology were analyzed by confocal laser scanning microscopy. Secretion of vascular endothelial growth factor (VEGF)-A was measured by enzyme-linked immunosorbent assay and expressions of iNOS and eNOS were investigated by real-time polymerase chain reaction. Cell numbers were higher in the control groups compared to the cells of titanium surfaces. Initially, hydrophilic titanium surfaces (modA and modSLA) showed lower cell numbers than hydrophobic surfaces (A and SLA). After 7 days smoother surfaces (A and modA) showed increased cell numbers compared to rougher surfaces (SLA and modSLA). Cell morphology of A, modA, and control surfaces was characterized by a multitude of pseudopodia and planar cell soma architecture. SLA and modSLA promoted small and plump cell soma with little quantity of pseudopodia. The lowest VEGF level was measured on A, the highest on modSLA. The highest eNOS and iNOS expressions were found on modA surfaces. The results of this study demonstrate that biological behaviors of EPCs can be influenced by different surfaces. The modSLA surface promotes an undifferentiated phenotype of EPCs that has the ability to secrete growth factors in great quantities. In

  19. Intravitreal itraconazole inhibits laser-induced choroidal neovascularization in rats.

    Directory of Open Access Journals (Sweden)

    Jeong Hun Bae

    Full Text Available Choroidal neovascularization (CNV is a major cause of severe visual loss in patients with age-related macular degeneration (AMD. Recently, itraconazole has shown potent and dose-dependent inhibition of tumor-associated angiogenesis. We evaluated the anti-angiogenic effect of itraconazole in a rat model of laser-induced CNV. After laser photocoagulation in each eye to cause CNV, right eyes were administered intravitreal injections of itraconazole; left eyes received balanced salt solution (BSS as controls. On day 14 after laser induction, fluorescein angiography (FA was used to assess abnormal vascular leakage. Flattened retinal pigment epithelium (RPE-choroid tissue complex was stained with Alexa Fluor 594-conjugated isolectin B4 to measure the CNV area and volume. Vascular endothelial growth factor receptor 2 (VEGFR2 mRNA and protein expression was determined 1, 4, 7, and 14 days after intravitreal injection by quantitative RT-PCR or Western blot. VEGF levels were analyzed by enzyme-linked immunosorbent assay (ELISA. Intravitreal itraconazole significantly reduced leakage from CNV as assessed by FA and CNV area and volume on flat mounts compared with intravitreal BSS (p = 0.002 for CNV leakage, p<0.001 for CNV area and volume. Quantitative RT-PCR showed significantly lower expression of VEGFR2 mRNA in the RPE-choroid complexes of itraconazole-injected eyes than those of BSS-injected eyes on days 7 and 14 (p = 0.003 and p = 0.006. Western blots indicated that VEGFR2 was downregulated after itraconazole treatment. ELISA showed a significant difference in VEGF level between itraconazole-injected and BSS-injected eyes on days 7 and 14 (p = 0.04 and p = 0.001. Our study demonstrated that intravitreal itraconazole significantly inhibited the development of laser-induced CNV in rats. Itraconazole had anti-angiogenic activity along with the reduction of VEGFR2 and VEGF levels. Itraconazole may prove beneficial for treating CNV as an alternative or

  20. Strategy to prime the host and cells to augment therapeutic efficacy of progenitor cells for patients with myocardial infarction

    Directory of Open Access Journals (Sweden)

    Jeehoon Kang

    2016-11-01

    Full Text Available Cell therapy in myocardial infarction (MI is an innovative strategy that is regarded as a rescue therapy to repair the damaged myocardium and to promote neovascularization for the ischemic border zone. Among several stem cell sources for this purpose, autologous progenitors from bone marrow or peripheral blood would be the most feasible and safest cell-source. Despite the theoretical benefit of cell therapy, this method is not widely adopted in the actual clinical practice due to its low therapeutic efficacy. Various methods have been used to augment the efficacy of cell therapy in MI, such as using different source of progenitors, genetic manipulation of cells, or priming of the cells or hosts (patients with agents. Among these methods, the strategy to augment the therapeutic efficacy of the autologous peripheral blood mononuclear cells by priming agents may be the most feasible and the safest method that can be applied directly to the clinic. In this review, we will discuss the current status and future directions of priming peripheral blood mononuclear cells or patients, as for cell therapy of MI.

  1. Heterogeneity of limbal basal epithelial progenitor cells.

    Science.gov (United States)

    Hayashida, Yasutaka; Li, Wei; Chen, Ying-Ting; He, Hua; Chen, Szu-yu; Kheirkah, Ahmad; Zhu, Ying-Tien; Matsumoto, Yukihiro; Tseng, Scheffer C G

    2010-11-01

    Although corneal epithelial stem cells (SCs) are located at the limbus between the cornea and the conjunctiva, not all limbal basal epithelial cells are SCs. Using 2 dispase digestions to remove different amounts of limbal basal epithelial cells for cross-sections, flat mounts, and cytospin preparations, double immunostaining to pancytokeratins (PCK) and vimentin (Vim) identified 3 p63+ epithelial progenitors such as PCK-/Vim+, PCK/Vim, and PCK-/Vim+ and 1 p63+ mesenchymal cell, PCK-/Vim+. PCK-/Vim- progenitors had the smallest cell size were 10-20 times more enriched on collagen I-coated dishes in the 5-minute rapid adherent fraction that contained the highest percentage of p63+ cells but the lowest percentage of cytokeratin12+ cells, and gave rise to high Ki67 labeling and vivid clonal growth. In contrast, PCK+/Vim+ and PCK+/Vim- progenitors were found more in the slow-adherent fraction and yielded poor clonal growth. PCK/Vim progenitors and clusters of PCK-/Vim+ mesenchymal cells, which were neither melanocytes nor Langerhans cells, were located in the limbal basal region. Therefore, differential expression of PCK and Vim helps identify small PCK-/Vim- cells as the most likely candidate for SCs among a hierarchy of heterogeneous limbal basal progenitors, and their close association with PCK-/Vim+ presumed "niche" cells.

  2. Evaluation of 10 AMD Associated Polymorphisms as a Cause of Choroidal Neovascularization in Highly Myopic Eyes.

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    Alvaro Velazquez-Villoria

    Full Text Available Choroidal neovascularization (CNV commonly occurs in age related macular degeneration and pathological myopia patients. In this study we conducted a case-control prospective study including 431 participants. The aim of this study was to determine the potential association between 10 single nucleotide polymorphisms (SNPs located in 4 different genetic regions (CFI, COL8A1, LIPC, and APOE, and choroidal neovascularization in age-related macular degeneration and the development of choroidal neovascularization in highly myopic eyes of a Caucasian population. Univariate and multivariate logistic regression analysis adjusted for age, sex and hypertension was performed for each allele, genotype and haplotype frequency analysis. We found that in the univariate analysis that both single-nucleotide polymorphisms in COL8A1 gene (rs13095226 and rs669676 together with age, sex and hypertension were significantly associated with myopic CNV development in Spanish patients (p0.05; however, analysis of the axial length between genotypes of rs13095226 revealed an important influence of COL8A1 in the development of CNV in high myopia. Furthermore we conducted a meta-analysis of COL8A1, CFI and LIPC genes SNPs (rs669676, rs10033900 and rs10468017 and found that only rs669676 of these SNPs were associated with high myopia neovascularization.

  3. Inhibition of corneal neovascularization by recombinant adenovirus-mediated sFlk-1 expression

    International Nuclear Information System (INIS)

    Yu Hui; Wu Jihong; Li Huiming; Wang Zhanli; Chen Xiafang; Tian Yuhua; Yi Miaoying; Ji Xunda; Ma Jialie; Huang Qian

    2007-01-01

    The interaction of vascular endothelial growth factor (VEGF) and its receptors (Flt-1, Flk-1/KDR) is correlated with neovascularization in the eyes. Therefore, blocking the binding of VEGF and the corresponding receptor has become critical for inhibiting corneal neovascularization. In this study, we have expressed the cDNA for sFlk-1 under the control of cytomegalovirus immediate-early promoter (CMV) from an E1/partial E3 deleted replication defective recombinant adenovirus, and Ad.sflk-1 expression was determined by Western blotting. We have shown that conditioned media from Ad.sflk-1-infected ARPE-19 cells significantly reduced VEGF-induced human umbilical vein endothelial cells (HUVEC) and murine endothelial cells (SVEC) proliferation in vitro compared with the control vector. In vivo, adenoviral vectors expressing green fluorescent protein alone (Ad.GFP) were utilized to monitor gene transfer to the cornea. Moreover, in the models of corneal neovascularization, the injection of Ad.sflk-1 (10 8 PFU) into the anterior chamber could significantly inhibit angiogenic changes compared with Ad.null-injected and vehicle-injected models. Immunohistochemical analysis showed that corneal endothelial cells and corneal stroma of cauterized rat eyes were efficiently transduced and expressed sFlk-1. These results not only support that adenoviral vectors are capable of high-level transgene expression but also demonstrate that Ad.sflk-1 gene therapy might be a feasible approach for inhibiting the development of corneal neovascularization

  4. Swept-source optical coherence tomography angiography for choroidal neovascularization after bevacizumab and photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Jesse J. Jung

    2016-04-01

    Conclusion: We report the first SS-OCTA images of successfully treated extrafoveal NV after combination PDT and ant-VEGF therapy. Early treatment of extrafoveal NV may improve our ability to treat mixed type 1 and 2 NV before these neovascular complexes mature from repetitive anti-VEGF treatment.

  5. Natural history of choroidal neovascularization after surgical induction in an animal model

    DEFF Research Database (Denmark)

    Lassota, Nathan; Kiilgaard, Jens Folke; la Cour, Morten

    2008-01-01

    PURPOSE: To study an expanded time course of surgically induced choroidal neovascularization (CNV) in a porcine model applying fluorescence angiography and immunohistology. METHODS: Twenty-two porcine eyes underwent vitrectomy, a retinal bleb was raised and the detached retina perforated using en...

  6. Lahore general hospital protocol for treatment of neovascular glaucoma caused by retinal disease

    International Nuclear Information System (INIS)

    Khaqan, H.A.; Haider, S.A.

    2013-01-01

    To evaluate efficacy of LGH (Lahore General Hospital) protocol for treatment of neovascular glaucoma caused by retinal diseases. Material and Methods: This case series was performed on 9 consecutive eyes of nine patients with uncontrolled neovascular glaucoma at Department of Ophthalmology, Unit II, Lahore General Hospital/PGMI, Lahore. All nine patients completed six months follow up. Among them 6 patients were having PDR (proliferative diabetic retinopathy) and 3 patients having CRVO (central retinal vein occlusion). LGH protocol for treatment of neovascular glaucoma was: To give intravitreal injection of avastin and then PRP (Pan Retinal Photocoagulation) or Trabeculectomy with MMC (Mitomycin C), if PRP and intravitreal avastin fails to control the intra ocular-pressure (IOP). Results: Three patients had IOP control after intravitreal injection of avastin and PRP, 5 patients had uncontrolled IOP after intravitreal avastin and two sessions of PRP, so they under went trabeculectomy with MMC. One patient had uncontrolled IOP despite of full treatment protocol. All other 8 patients IOP remained stable for six months. Conclusion: Significant decrease in intraocular pressure was achieved after observing LGH protocol for treatment of NVG (Neovascular Glaucoma) caused by retinal diseases. (author)

  7. Intravitreal bevacizumab as therapy for refractory neovascular glaucoma secondary to iris metastasis of breast carcinoma

    Directory of Open Access Journals (Sweden)

    Stephanie Vale

    2018-03-01

    Conclusions & importance: A single intravitreal bevacizumab injection may be sufficient to achieve palliative control of neovascular glaucoma secondary to iris breast cancer metastasis. To our knowledge, this is the first case report in which a single intravitreal bevacizumab injection was used for the effective management of this condition.

  8. Hedgehog Signaling Components Are Expressed in Choroidal Neovascularization in Laser-induced Retinal Lesion

    International Nuclear Information System (INIS)

    Nochioka, Katsunori; Okuda, Hiroaki; Tatsumi, Kouko; Morita, Shoko; Ogata, Nahoko; Wanaka, Akio

    2016-01-01

    Choroidal neovascularization is one of the major pathological changes in age-related macular degeneration, which causes devastating blindness in the elderly population. The molecular mechanism of choroidal neovascularization has been under extensive investigation, but is still an open question. We focused on sonic hedgehog signaling, which is implicated in angiogenesis in various organs. Laser-induced injuries to the mouse retina were made to cause choroidal neovascularization. We examined gene expression of sonic hedgehog, its receptors (patched1, smoothened, cell adhesion molecule down-regulated by oncogenes (Cdon) and biregional Cdon-binding protein (Boc)) and downstream transcription factors (Gli1-3) using real-time RT-PCR. At seven days after injury, mRNAs for Patched1 and Gli1 were upregulated in response to injury, but displayed no upregulation in control retinas. Immunohistochemistry revealed that Patched1 and Gli1 proteins were localized to CD31-positive endothelial cells that cluster between the wounded retina and the pigment epithelium layer. Treatment with the hedgehog signaling inhibitor cyclopamine did not significantly decrease the size of the neovascularization areas, but the hedgehog agonist purmorphamine made the areas significantly larger than those in untreated retina. These results suggest that the hedgehog-signaling cascade may be a therapeutic target for age-related macular degeneration

  9. Single-Chain Antibody Fragment VEGF Inhibitor RTH258 for Neovascular Age-Related Macular Degeneration

    DEFF Research Database (Denmark)

    Holz, Frank G; Dugel, Pravin U.; Weissgerber, Georges

    2016-01-01

    Purpose To assess the safety and efficacy of different doses of RTH258 applied as single intravitreal administration compared with ranibizumab 0.5 mg in patients with neovascular age-related macular degeneration (AMD). Design Six-month, phase 1/2, prospective, multicenter, double-masked, randomized...

  10. Visual outcomes in relation to time to treatment in neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Rasmussen, Annette; Bloch, Sara Brandi; Fuchs, Josefine

    2015-01-01

    PURPOSE: To study the relation between the interval from diagnosis to initiation of intravitreal injection therapy and visual outcome in neovascular age-related macular degeneration (nAMD) and to report changes over time in fellow-eye status. METHODS: Retrospective chart review. The study included...

  11. T-cell differentiation and CD56+ levels in polypoidal choroidal vasculopathy and neovascular age-related macular degeneration.

    Science.gov (United States)

    Subhi, Yousif; Nielsen, Marie Krogh; Molbech, Christopher Rue; Oishi, Akio; Singh, Amardeep; Nissen, Mogens Holst; Sørensen, Torben Lykke

    2017-11-20

    Polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (AMD) are prevalent age-related diseases characterized by exudative changes in the macula. Although they share anatomical and clinical similarities, they are also distinctly characterized by their own features, e.g. vascular abnormalities in PCV and drusen-mediated progression in neovascular AMD. PCV remains etiologically uncharacterized, and ongoing discussion is whether PCV and neovascular AMD share the same etiology or constitute two substantially different diseases. In this study, we investigated T-cell differentiation and aging profile in human patients with PCV, patients with neovascular AMD, and age-matched healthy control individuals. Fresh venous blood was prepared for flow cytometry to investigate CD4 + and CD8 + T-cell differentiation (naïve, central memory, effector memory, effector memory CD45ra + ), loss of differentiation markers CD27 and CD28, and expression of aging marker CD56. Patients with PCV were similar to the healthy controls in all aspects. In patients with neovascular AMD we found significantly accelerated T-cell differentiation (more CD28 - CD27 - cells) and aging (more CD56 + cells) in the CD8 + T-cell compartment. These findings suggest that PCV and neovascular AMD are etiologically different in terms of T cell immunity, and that neovascular AMD is associated with T-cell immunosenescence.

  12. Haemopoietic progenitor cells in human peripheral blood

    International Nuclear Information System (INIS)

    Zwaan, F.E.

    1980-01-01

    The purpose of the investigation reported is to purify haemopoietic progenitor cells from human peripheral blood using density gradient centrifugation in order to isolate a progenitor cell fraction without immunocompetent cells. The purification technique of peripheral blood flow colony forming unit culture (CFU-c) by means of density gradient centrifugation and a combined depletion of various rosettes is described. The results of several 'in vitro' characteristics of purified CFU-c suspensions and of the plasma clot diffusion chamber culture technique are presented. Irradiation studies revealed that for both human bone marrow and peripheral blood the CFU-c were less radioresistant than clusters. Elimination of monocytes (and granulocytes) from the test suspensions induced an alteration in radiosensitivity pararmeters. The results obtained with the different techniques are described by analysing peripheral progenitor cell activity in myeloproliferative disorders. (Auth.)

  13. Honokiol inhibits pathological retinal neovascularization in oxygen-induced retinopathy mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Vavilala, Divya Teja [Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, MO (United States); O’Bryhim, Bliss E. [Department of Ophthalmology, University of Kansas Medical Center, Kansas City, KS (United States); Ponnaluri, V.K. Chaithanya [Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, MO (United States); White, R. Sid; Radel, Jeff [Department of Ophthalmology, University of Kansas Medical Center, Kansas City, KS (United States); Symons, R.C. Andrew [Department of Ophthalmology, University of Kansas Medical Center, Kansas City, KS (United States); Ophthalmology Department, Royal Melbourne Hospital, University of Melbourne, Victoria (Australia); Department of Surgery, Royal Melbourne Hospital, University of Melbourne, Victoria (Australia); Mukherji, Mridul, E-mail: mukherjim@umkc.edu [Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, MO (United States)

    2013-09-06

    Highlights: •Aberrant activation of HIF pathway is the underlying cause of ischemic neovascularization. •Honokiol has better therapeutic index as a HIF inhibitor than digoxin and doxorubicin. •Daily IP injection of honokiol in OIR mouse model reduced retinal neovascularization. •Honokiol also prevents vaso-obliteration, the characteristic feature of the OIR model. •Honokiol enhanced physiological revascularization of the retinal vascular plexuses. -- Abstract: Aberrant activation of the hypoxia inducible factor (HIF) pathway is the underlying cause of retinal neovascularization, one of the most common causes of blindness worldwide. The HIF pathway also plays critical roles during tumor angiogenesis and cancer stem cell transformation. We have recently shown that honokiol is a potent inhibitor of the HIF pathway in a number of cancer and retinal pigment epithelial cell lines. Here we evaluate the safety and efficacy of honokiol, digoxin, and doxorubicin, three recently identified HIF inhibitors from natural sources. Our studies show that honokiol has a better safety to efficacy profile as a HIF inhibitor than digoxin and doxorubicin. Further, we show for the first time that daily intraperitoneal injection of honokiol starting at postnatal day (P) 12 in an oxygen-induced retinopathy (OIR) mouse model significantly reduced retinal neovascularization at P17. Administration of honokiol also prevents the oxygen-induced central retinal vaso-obliteration, characteristic feature of the OIR model. Additionally, honokiol enhanced physiological revascularization of the retinal vascular plexuses. Since honokiol suppresses multiple pathways activated by HIF, in addition to the VEGF signaling, it may provide advantages over current treatments utilizing specific VEGF antagonists for ocular neovascular diseases and cancers.

  14. Efficacy of intravitreal ranibizumab combined with Ahmed glaucoma valve implantation for the treatment of neovascular glaucoma.

    Science.gov (United States)

    Tang, Min; Fu, Yang; Wang, Ying; Zheng, Zhi; Fan, Ying; Sun, Xiaodong; Xu, Xun

    2016-01-09

    Neovascular glaucoma is a refractive glaucoma. Recently, anti-VEGF factors have been used alone or in combination for the treatment of neovascular glaucoma. However, the medium- and long-term efficacy of such drugs remains to be evaluated. This study was to determine the efficacy of intravitreal ranibizumab combined with Ahmed glaucoma valve implantation for the treatment of neovascular glaucoma. In this prospective non-randomized study, 43 neovascular glaucoma patients (43 eyes) were assigned to receive either 0.5 mg intravitreal ranibizumab for three to 14 days before Ahmed glaucoma valve implantation (injection group, n = 21) or Ahmed glaucoma valve implantation alone (control group, n = 22). The patients were followed up for six to 12 months. Differences in surgical success rate, intraocular pressure, best corrected visual acuity, anti-glaucoma medications and postoperative complications were compared between the two groups. Surgical success was defined as IOP > = 6 mm Hg and glaucoma medications, and without severe complications or reoperation. Of the 43 patients, 40 completed the 6-month follow-up and 37 completed the 1-year follow-up. Success rate was 73.7% vs. 71.4% at six months and 72.2% vs. 68.4% at 12 months in the injection group and the control group respectively. No significant difference was noted between the two groups (six months: P = 0.87, 12 months: P = 1.00). There were no significant differences in the two groups with respect to intraocular pressure, best corrected visual acuity, anti-glaucoma medications or postoperative complications at six months or 12 months. Single intravitreal ranibizumab (0.5 mg) before surgery has no significant effect on the medium- or long-term outcomes of neovascular glaucoma treated with Ahmed glaucoma valve implantation. Chinese Clinical Trial Registry ( ChiCTR-OOC-14005709, Trial registration date: 2014-12-01).

  15. IQGAP1 is involved in post-ischemic neovascularization by regulating angiogenesis and macrophage infiltration.

    Directory of Open Access Journals (Sweden)

    Norifumi Urao

    2010-10-01

    Full Text Available Neovascularization is an important repair mechanism in response to ischemic injury and is dependent on inflammation, angiogenesis and reactive oxygen species (ROS. IQGAP1, an actin-binding scaffold protein, is a key regulator for actin cytoskeleton and motility. We previously demonstrated that IQGAP1 mediates vascular endothelial growth factor (VEGF-induced ROS production and migration of cultured endothelial cells (ECs; however, its role in post-ischemic neovascularization is unknown.Ischemia was induced by left femoral artery ligation, which resulted in increased IQGAP1 expression in Mac3(+ macrophages and CD31(+ capillary-like ECs in ischemic legs. Mice lacking IQGAP1 exhibited a significant reduction in the post-ischemic neovascularization as evaluated by laser Doppler blood flow, capillary density and α-actin positive arterioles. Furthermore, IQGAP1(-/- mice showed a decrease in macrophage infiltration and ROS production in ischemic muscles, leading to impaired muscle regeneration and increased necrosis and fibrosis. The numbers of bone marrow (BM-derived cells in the peripheral blood were not affected in these knockout mice. BM transplantation revealed that IQGAP1 expressed in both BM-derived cells and tissue resident cells, such as ECs, is required for post-ischemic neovascularization. Moreover, thioglycollate-induced peritoneal macrophage recruitment and ROS production were inhibited in IQGAP1(-/- mice. In vitro, IQGAP1(-/- BM-derived macrophages showed inhibition of migration and adhesion capacity, which may explain the defective macrophage recruitment into the ischemic tissue in IQGAP1(-/- mice.IQGAP1 plays a key role in post-ischemic neovascularization by regulating, not only, ECs-mediated angiogenesis but also macrophage infiltration as well as ROS production. Thus, IQGAP1 is a potential therapeutic target for inflammation- and angiogenesis-dependent ischemic cardiovascular diseases.

  16. Intravitreal Bevacizumab injection combined duplex technique in treatment of neovascular glaucoma

    Directory of Open Access Journals (Sweden)

    Zheng-Jun Hu

    2015-05-01

    Full Text Available AIM: To observe the clinical curative effect of intravitreal Bevacizumab injection combined duplex technique in treatment of neovascular glaucoma(NVG.METHODS:Totally 25 eyes of 25 patients with NVG who underwent intravitreal Bevacizumab injection of 1.0mg(0.05mL, after the regression of iris neovascularization, 5 eyes with anterior chamber paracentesis fluid auxiliary controlled intraocular pressure. After 2wk, patients were treated by trabeculectomy and phacomulsification(9 eyes were implanted intraocular lens. The changes and complications of intraocular pressure, visual acuity, corneas and neovessels were observed after surgery, and followed up 12mo.RESULTS:After injection Bevacizumab in 25 eyes, iris neovascularization of 20 eyes subsided in 3~5d, and 5 eyes subsided in 7d. After controlling intraocular pressure, count of the corneal endothelial cell were 1 629±226mm2, and none suffered decompensation of corneal endothelium after two-surgery of trabeculectomy and phacomulsification. After followed up 12mo, intraocular pressure of 20 eyes were controlled in normal range; 2 eyes could control in normal range after treated by a kind of anti-glaucoma medicine and 3 eyes was 34~38mmHg after treated by anti-glaucoma medicine. 9 eyes had improved vision after implanted intraocular lens.CONCLUSION:Intravitreal Bevacizumab injection can subside iris and anterior chamber angle neovascularization effectively in a short time and reduce intraocular pressure. It can also reduce the risk of bleeding during operation or after operation. Intravitreal Bevacizumab injection combined with two-surgery of trabeculectomy and phacomulsification can treat neovascular glaucoma effectively.

  17. Analysis of intravitreal using of anti vegf-medications for diseases of fundus accompanied by exudation and neovascularization

    Directory of Open Access Journals (Sweden)

    N. G. Zavgorodnya

    2013-08-01

    Full Text Available Nowadays, new methods of treatment of choroidal neovascularization are being actively developed and introduced in exudative form of age-related macular degeneration (AMD, complicated myopia, diabetic retinopathy and post-thrombotic retinopathy. Medications that block vascular endothelial growth factor (VEGF, which is the main link in the pathogenesis of retinal neovascularization and hyperfiltration, have become widespread. It is known that damage of endothelial cells of retinal vessels occurs in consequence of oxidative stress that leads to the death of pericytes, hyperfiltration of plasma from the vascular bed, hemorrhages and retinal hypoxia. The intracellular concentration of specific protein that regulates the transcription of genes (HIF-1 increases in response to hypoxic damage in the cells of the retina, which leads to increased transcription of the VEGF gene, which acts directly on the epithelium providing regeneration, stimulating the proliferation and neovascularization. Considering this, anti-VEGF medications have found their application in the treatment of choroidal neovascularization in clinical practice. Today, two preparations that block VEGF: selective (pegaptanib and non-selective (ranibizumab are used mostly common. The purpose of this investigation was to study the effectiveness of anti-VEGF medications in patients with choroidal neovascularization of different genesis. The analysis presents the results of 50 patients (50 eyes treatment with choroidal neovascularization on the background of various diseases of the retina. Pegaptanib ("Macugen" was used for the treatment of 35 patients (35 eyes, the rest (15 eyes - ranibizumab ("Lucentis". According to fluorescein angiography the subretinal neovascular membrane was in the stage of activity in all eyes. The effectiveness of the treatment was assessed by visometry, ophthalmoscopy, optical coherence tomography and fluorescein angiography. Application of intravitreal injection of

  18. Butein Inhibits Angiogenesis of Human Endothelial Progenitor Cells via the Translation Dependent Signaling Pathway

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    Ching-Hu Chung

    2013-01-01

    Full Text Available Compelling evidence indicates that bone marrow-derived endothelial progenitor cells (EPCs can contribute to postnatal neovascularization and tumor angiogenesis. EPCs have been shown to play a “catalytic” role in metastatic progression by mediating the angiogenic switch. Understanding the pharmacological functions and molecular targets of natural products is critical for drug development. Butein, a natural chalcone derivative, has been reported to exert potent anticancer activity. However, the antiangiogenic activity of butein has not been addressed. In this study, we found that butein inhibited serum- and vascular endothelial growth factor- (VEGF- induced cell proliferation, migration, and tube formation of human EPCs in a concentration dependent manner without cytotoxic effect. Furthermore, butein markedly abrogated VEGF-induced vessels sprouting from aortic rings and suppressed microvessel formation in the Matrigel implant assay in vivo. In addition, butein concentration-dependently repressed the phosphorylation of Akt, mTOR, and the major downstream effectors, p70S6K, 4E-BP1, and eIF4E in EPCs. Taken together, our results demonstrate for the first time that butein exhibits the antiangiogenic effect both in vitro and in vivo by targeting the translational machinery. Butein is a promising angiogenesis inhibitor with the potential for treatment of cancer and other angiogenesis-related diseases.

  19. Brucella abortus-infected B cells induce osteoclastogenesis.

    Science.gov (United States)

    Pesce Viglietti, Ayelén Ivana; Arriola Benitez, Paula Constanza; Giambartolomei, Guillermo Hernán; Delpino, María Victoria

    2016-09-01

    Brucella abortus is an intracellular bacterium that establishes lifelong infections in livestock and humans although the mechanisms of its chronicity are poorly understood. Activated B cells have long lifespan and B. abortus infection activates B cells. Our results indicate that the direct infection of B cells with B. abortus induced matrix metalloproteinase-9 (MMP-9), receptor activator for NF κB ligand (RANKL), tumor necrosis factor (TNF)-α and interleukin (IL)-6 secretion. In addition, supernatants from B. abortus-infected B cells induced bone marrow-derived monocytes to undergo osteoclastogenesis. Using osteoprotegerin, RANKL's decoy receptor, we determined that RANKL is involved in osteoclastogenesis induced by supernatants from B. abortus-infected B cells. The results presented here shed light on how the interactions of B. abortus with B cells may have a role in the pathogenesis of brucellar osteoarticular disease. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  20. The apoptosis of CHO cells induced by X-rays

    International Nuclear Information System (INIS)

    Lu Zhaohong; Zhao Jingyong; Zhu Mingqing; Shi Xijin; Wang Chunlei

    2004-01-01

    The work is to study the mechanism of toxic effects on reproductive system and apoptosis of Chinese hamster ovary (CHO) cells induced by X-rays. CHO cell was exposed to X-rays 2 to 20 Gy. Apoptosis and morphological changes of the cells were observed by fluorescent microscopy and flow cytometry analyzer with double staining with Annexin V/PI. The apoptosis could be observed at 24, 48 and 72h after the exposure, but it was more obvious 48 and 72 h after the exposure. Rate of the apoptosis increased along with radiation dose were elevated. Some morphological changes, such as irregular agglomerate of chromatins, pycnosis and periphery distribution of nuclei, crescent-moon-like cells, small apoptosis body, were observed. Radiation results DNA damage in the CHO cells, and the damage cannot be repaired, hence the induced cell apoptosis. (authors)

  1. X Inactivation and Progenitor Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ruben Agrelo

    2011-04-01

    Full Text Available In mammals, silencing of one of the two X chromosomes is necessary to achieve dosage compensation. The 17 kb non-coding RNA called Xist triggers X inactivation. Gene silencing by Xist can only be achieved in certain contexts such as in cells of the early embryo and in certain hematopoietic progenitors where silencing factors are present. Moreover, these epigenetic contexts are maintained in cancer progenitors in which SATB1 has been identified as a factor related to Xist-mediated chromosome silencing.

  2. Tissue engineering and the use of stem/progenitor cells for airway epithelium repair

    Directory of Open Access Journals (Sweden)

    GM Roomans

    2010-06-01

    Full Text Available Stem/progenitor cells can be used to repair defects in the airway wall, resulting from e.g., tumors, trauma, tissue reactions following long-time intubations, or diseases that are associated with epithelial damage. Several potential sources of cells for airway epithelium have been identified. These can be divided into two groups. The first group consists of endogenous progenitor cells present in the respiratory tract. This group can be subdivided according to location into (a a ductal cell type in the submucosal glands of the proximal trachea, (b basal cells in the intercartilaginous zones of the lower trachea and bronchi, (c variant Clara cells (Clarav-cells in the bronchioles and (d at the junctions between the bronchioles and the alveolar ducts, and (e alveolar type II cells. This classification of progenitor cell niches is, however, controversial. The second group consists of exogenous stem cells derived from other tissues in the body. This second group can be subdivided into: (a embryonic stem (ES cells, induced pluripotent stem (iPS cells, or amniotic fluid stem cells, (b side-population cells from bone marrow or epithelial stem cells present in bone marrow or circulation and (c fat-derived mesenchymal cells. Airway epithelial cells can be co-cultured in a system that includes a basal lamina equivalent, extracellular factors from mesenchymal fibroblasts, and in an air-liquid interface system. Recently, spheroid-based culture systems have been developed. Several clinical applications have been suggested: cystic fibrosis, acute respiratory distress syndrome, chronic obstructive lung disease, pulmonary fibrosis, pulmonary edema, and pulmonary hypertension. Clinical applications so far are few, but include subglottic stenosis, tracheomalacia, bronchiomalacia, and emphysema.

  3. Cataclysmic Variables as Supernova Ia Progenitors

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    Stella Kafka

    2012-06-01

    Full Text Available Although the identification of the progenitors of type Ia supernovae (SNeIa remains controversial, it is generally accepted that they originate from binary star systems in which at least one component is a carbon-oxygen white dwarf (WD; those systems are grouped under the wide umbrella of cataclysmic variables. Current theories for SNeIa progenitors hold that, either via Roche lobe overflow of the companion or via a wind, the WD accumulates hydrogen or helium rich material which is then burned to C and O onto the WD’s surface. However, the specifics of this scenario are far from being understood or defined, allowing for a wealth of theories fighting for attention and a dearth of observations to support them. I discuss the latest attempts to identify and study those controversial SNeIa progenitors. I also introduce the most promising progenitor in hand and I present observational diagnostics that can reveal more members of the category.

  4. Cardiac Progenitor Cell Extraction from Human Auricles

    KAUST Repository

    Di Nardo, Paolo; Pagliari, Francesca

    2017-01-01

    by precursor cells mostly embedded into the heart apex and in the atria. We have shown that an elective region of progenitor cell embedding is represented by the auricles, non-contractile atria appendages that can be easily sampled without harming the patient

  5. Efficacy and Safety of Monthly versus Quarterly Ranibizumab Treatment in Neovascular Age-related Macular Degeneration: The EXCITE Study

    NARCIS (Netherlands)

    Schmidt-Erfurth, Ursula; Eldem, Bora; Guymer, Robyn; Korobelnik, Jean-Franc̦ois; Schlingemann, Reinier O.; Axer-Siegel, Ruth; Wiedemann, Peter; Simader, Christian; Gekkieva, Margarita; Weichselberger, Andreas

    2011-01-01

    Objective: To demonstrate noninferiority of a quarterly treatment regimen to a monthly regimen of ranibizumab in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Design: A 12-month, multicenter, randomized, double-masked,

  6. SUPERNOVA REMNANT PROGENITOR MASSES IN M31

    Energy Technology Data Exchange (ETDEWEB)

    Jennings, Zachary G.; Williams, Benjamin F.; Dalcanton, Julianne J.; Gilbert, Karoline M.; Fouesneau, Morgan; Weisz, Daniel R. [Department of Astronomy, University of Washington Seattle, Box 351580, WA 98195 (United States); Murphy, Jeremiah W. [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Dolphin, Andrew E., E-mail: zachjenn@uw.edu, E-mail: adolphin@raytheon.com [Raytheon, 1151 East Hermans Road, Tucson, AZ 85706 (United States)

    2012-12-10

    Using Hubble Space Telescope photometry, we age-date 59 supernova remnants (SNRs) in the spiral galaxy M31 and use these ages to estimate zero-age main-sequence masses (M{sub ZAMS}) for their progenitors. To accomplish this, we create color-magnitude diagrams (CMDs) and employ CMD fitting to measure the recent star formation history of the regions surrounding cataloged SNR sites. We identify any young coeval population that likely produced the progenitor star, then assign an age and uncertainty to that population. Application of stellar evolution models allows us to infer the M{sub ZAMS} from this age. Because our technique is not contingent on identification or precise location of the progenitor star, it can be applied to the location of any known SNRs. We identify significant young star formation around 53 of the 59 SNRs and assign progenitor masses to these, representing a factor of {approx}2 increase over currently measured progenitor masses. We consider the remaining six SNRs as either probable Type Ia candidates or the result of core-collapse progenitors that have escaped their birth sites. In general, the distribution of recovered progenitor masses is bottom-heavy, showing a paucity of the most massive stars. If we assume a single power-law distribution, dN/dM{proportional_to}M{sup {alpha}}, then we find a distribution that is steeper than a Salpeter initial mass function (IMF) ({alpha} = -2.35). In particular, we find values of {alpha} outside the range -2.7 {>=} {alpha} {>=} -4.4 to be inconsistent with our measured distribution at 95% confidence. If instead we assume a distribution that follows a Salpeter IMF up to some maximum mass, then we find that values of M{sub Max} > 26 are inconsistent with the measured distribution at 95% confidence. In either scenario, the data suggest that some fraction of massive stars may not explode. The result is preliminary and requires more SNRs and further analysis. In addition, we use our distribution to estimate a

  7. Relapse of choroidal neovascularization in Bietti's crystalline retinopathy following anti-vascular endothelial growth factor therapy: A case report

    OpenAIRE

    HUA, RUI; CHEN, KANG; HU, YUEDONG; WANG, XINLING; CHEN, LEI

    2015-01-01

    Choroidal neovascularization secondary to retinitis pigmentosa is rarely observed in clinical practice. The present study describes a case of atypical retinitis pigmentosa, crystalline retinal pigmentary degeneration, complicated by choroidal neovascularization (CNV) in a 26-year-old man presenting with blurred vision in the right eye. Heidelberg multimodality imaging was performed to achieve a confirmed diagnosis. Bevacizumab was injected once intravitreally. The 3-month follow-up included v...

  8. Clinical and histological findings after intravitreal injection of bevacizumab (Avastin) in a porcine model of choroidal neovascularization

    DEFF Research Database (Denmark)

    Lassota, Nathan; Prause, Jan Ulrik; Scherfig, Erik

    2010-01-01

    PURPOSE: To examine the effect of intravitreally injected bevacizumab (Avastin) on the histological and angiographic morphology of choroidal neovascularization (CNV) in a masked and placebo-controlled animal study. METHODS: Choroidal neovascularization was induced surgically in 11 porcine eyes by...... these membranes. After a single injection, bevacizumab did not exhibit a size reducing effect on CNV, but it was still present in the membranes 14 days after intravitreal injection....

  9. A 4-Year Longitudinal Study of 555 Patients Treated with Ranibizumab for Neovascular Age-related Macular Degeneration

    DEFF Research Database (Denmark)

    Rasmussen, Annette; Bloch, Sara B; Fuchs, Josefine

    2013-01-01

    To investigate the visual outcome, pattern of discontinuation, ocular complications, and mortality of patients treated with a variable ranibizumab dosing regimen for neovascular age-related macular degeneration (AMD) for 4 years.......To investigate the visual outcome, pattern of discontinuation, ocular complications, and mortality of patients treated with a variable ranibizumab dosing regimen for neovascular age-related macular degeneration (AMD) for 4 years....

  10. Characterization of Hemagglutinin Negative Botulinum Progenitor Toxins

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    Suzanne R. Kalb

    2017-06-01

    Full Text Available Botulism is a disease involving intoxication with botulinum neurotoxins (BoNTs, toxic proteins produced by Clostridium botulinum and other clostridia. The 150 kDa neurotoxin is produced in conjunction with other proteins to form the botulinum progenitor toxin complex (PTC, alternating in size from 300 kDa to 500 kDa. These progenitor complexes can be classified into hemagglutinin positive or hemagglutinin negative, depending on the ability of some of the neurotoxin-associated proteins (NAPs to cause hemagglutination. The hemagglutinin positive progenitor toxin complex consists of BoNT, nontoxic non-hemagglutinin (NTNH, and three hemagglutinin proteins; HA-70, HA-33, and HA-17. Hemagglutinin negative progenitor toxin complexes contain BoNT and NTNH as the minimally functional PTC (M-PTC, but not the three hemagglutinin proteins. Interestingly, the genome of hemagglutinin negative progenitor toxin complexes comprises open reading frames (orfs which encode for three proteins, but the existence of these proteins has not yet been extensively demonstrated. In this work, we demonstrate that these three proteins exist and form part of the PTC for hemagglutinin negative complexes. Several hemagglutinin negative strains producing BoNT/A, /E, and /F were found to contain the three open reading frame proteins. Additionally, several BoNT/A-containing bivalent strains were examined, and NAPs from both genes, including the open reading frame proteins, were associated with BoNT/A. The open reading frame encoded proteins are more easily removed from the botulinum complex than the hemagglutinin proteins, but are present in several BoNT/A and /F toxin preparations. These are not easily removed from the BoNT/E complex, however, and are present even in commercially-available purified BoNT/E complex.

  11. Origin of hemopoietic stromal progenitor cells in chimeras

    International Nuclear Information System (INIS)

    Chertkov, J.L.; Drize, N.J.; Gurevitch, O.A.; Samoylova, R.S.

    1985-01-01

    Intravenously injected bone marrow cells do not participate in the regeneration of hemopoietic stromal progenitors in irradiated mice, nor in the curetted parts of the recipient's marrow. The hemopoietic stromal progenitors in allogeneic chimeras are of recipient origin. The adherent cell layer (ACL) of long-term cultures of allogeneic chimera bone marrow contains only recipient hemopoietic stromal progenitors. However, in ectopic hemopoietic foci produced by marrow implantation under the renal capsule and repopulated by the recipient hemopoietic cells after irradiation and reconstitution by syngeneic hemopoietic cells, the stromal progenitors were of implant donor origin, as were stromal progenitors of the ACL in long-term cultures of hemopoietic cells from ectopic foci. Our results confirm that the stromal and hemopoietic progenitors differ in origin and that hemopoietic stromal progenitors are not transplantable by the intravenous route in mice

  12. PSGL-1–mediated activation of EphB4 increases the proangiogenic potential of endothelial progenitor cells

    Science.gov (United States)

    Foubert, Philippe; Silvestre, Jean-Sébastien; Souttou, Boussad; Barateau, Véronique; Martin, Coralie; Ebrahimian, Téni G.; Leré-Déan, Carole; Contreres, Jean Olivier; Sulpice, Eric; Levy, Bernard I.; Plouët, Jean; Tobelem, Gérard; Le Ricousse-Roussanne, Sophie

    2007-01-01

    Endothelial progenitor cell (EPC) transplantation has beneficial effects for therapeutic neovascularization; however, only a small proportion of injected cells home to the lesion and incorporate into the neocapillaries. Consequently, this type of cell therapy requires substantial improvement to be of clinical value. Erythropoietin-producing human hepatocellular carcinoma (Eph) receptors and their ephrin ligands are key regulators of vascular development. We postulated that activation of the EphB4/ephrin-B2 system may enhance EPC proangiogenic potential. In this report, we demonstrate in a nude mouse model of hind limb ischemia that EphB4 activation with an ephrin-B2–Fc chimeric protein increases the angiogenic potential of human EPCs. This effect was abolished by EphB4 siRNA, confirming that it is mediated by EphB4. EphB4 activation enhanced P selectin glycoprotein ligand-1 (PSGL-1) expression and EPC adhesion. Inhibition of PSGL-1 by siRNA reversed the proangiogenic and adhesive effects of EphB4 activation. Moreover, neutralizing antibodies to E selectin and P selectin blocked ephrin-B2–Fc–stimulated EPC adhesion properties. Thus, activation of EphB4 enhances EPC proangiogenic capacity through induction of PSGL-1 expression and adhesion to E selectin and P selectin. Therefore, activation of EphB4 is an innovative and potentially valuable therapeutic strategy for improving the recruitment of EPCs to sites of neovascularization and thereby the efficiency of cell-based proangiogenic therapy. PMID:17510705

  13. Intravitreal bevacizumab for treatment of choroidal neovascularization associated with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Pukhraj Rishi

    2012-01-01

    Full Text Available A 12-year-old girl, diagnosed of osteogenesis imperfecta, presented with sudden visual loss in the left eye. Investigations revealed an active choroidal neovascular membrane. She underwent treatment with intravitreal Bevacizumab (1.25 mg/0.05 ml. Follow-up at 1 month revealed the development of lacquer crack running through the macula, underlying the fovea. The patient received two re-treatments at 1-month intervals, following which the choroidal neovascularization (CNV regressed completely. However, further progression of lacquer cracks was noted. At the last follow-up, 6 months following the last injection, the fundus remained stable and vision was maintained at 20/200. Considering the natural history of the disease and the increased risk of rupture of the Bruch′s membrane in such eyes, the possible complication of a lacquer crack developing must be borne in mind, before initiating treatment.

  14. Bilateral choroidal neovascularization response to unilateral intravitreal Ranibizumab injection in a patient with angioid streaks

    Directory of Open Access Journals (Sweden)

    Otacílio de Oliveira Maia Júnior

    2013-08-01

    Full Text Available Report of a 48 year-old male with bilateral decrease in vision due to choroidal neovascularization secondary to angioid streaks. Best corrected visual acuity was 20/80 in the right eye and counting fingers at 2 meters on the left eye. Patient underwent intravitreal injection of Ranibizumab (Lucentis in the eye with worse visual acuity. Fifteen days after treatment patient reported better visual acuity on the fellow eye, which was measured to be 20/25. Treatment result was evaluated with visual acuity and optical coherence tomography. The effect of ranibizumab was observed in the treated eye, but the fellow eye had complete resolution of the choroidal neovascularization complex. This result may be a response to systemic absorption of the medication.

  15. Accelerated oxygen-induced retinopathy is a reliable model of ischemia-induced retinal neovascularization.

    Science.gov (United States)

    Villacampa, Pilar; Menger, Katja E; Abelleira, Laura; Ribeiro, Joana; Duran, Yanai; Smith, Alexander J; Ali, Robin R; Luhmann, Ulrich F; Bainbridge, James W B

    2017-01-01

    Retinal ischemia and pathological angiogenesis cause severe impairment of sight. Oxygen-induced retinopathy (OIR) in young mice is widely used as a model to investigate the underlying pathological mechanisms and develop therapeutic interventions. We compared directly the conventional OIR model (exposure to 75% O2 from postnatal day (P) 7 to P12) with an alternative, accelerated version (85% O2 from P8 to P11). We found that accelerated OIR induces similar pre-retinal neovascularization but greater retinal vascular regression that recovers more rapidly. The extent of retinal gliosis is similar but neuroretinal function, as measured by electroretinography, is better maintained in the accelerated model. We found no systemic or maternal morbidity in either model. Accelerated OIR offers a safe, reliable and more rapid alternative model in which pre-retinal neovascularization is similar but retinal vascular regression is greater.

  16. Neuroblast survival depends on mature vascular network formation after mouse stroke: role of endothelial and smooth muscle progenitor cell co-administration.

    Science.gov (United States)

    Nih, Lina R; Deroide, Nicolas; Leré-Déan, Carole; Lerouet, Dominique; Soustrat, Mathieu; Levy, Bernard I; Silvestre, Jean-Sébastien; Merkulova-Rainon, Tatiana; Pocard, Marc; Margaill, Isabelle; Kubis, Nathalie

    2012-04-01

    Pro-angiogenic cell-based therapies constitute an interesting and attractive approach to enhancing post-stroke neurogenesis and decreasing neurological deficit. However, most new stroke-induced neurons die during the first few weeks after ischemia, thus impairing total recovery. Although the neovascularization process involves different cell types and various growth factors, most cell therapy protocols are based on the biological effects of single-cell-type populations or on the administration of heterogeneous populations of progenitors, namely human cord blood-derived CD34(+) cells, with scarce vascular progenitor cells. Tight cooperation between endothelial cells and smooth muscle cells/pericytes is critical for the development of functional neovessels. We hypothesized that neuroblast survival in stroke brain depends on mature vascular network formation. In this study, we injected a combination of endothelial progenitor cells (EPCs) and smooth muscle progenitor cells (SMPCs), isolated from human umbilical cord blood, into a murine model of permanent focal ischemia induced by middle cerebral artery occlusion. The co-administration of SMPCs and EPCs induced enhanced angiogenesis and vascular remodeling in the peri-infarct and infarct areas, where vessels exhibited a more mature phenotype. This activation of vessel growth resulted in the maintenance of neurogenesis and neuroblast migration to the peri-ischemic cortex. Our data suggest that a mature vascular network is essential for neuroblast survival after cerebral ischemia, and that co-administration of EPCs and SMPCs may constitute a novel therapeutic strategy for improving the treatment of stroke. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  17. Quality of optometry referrals to neovascular age-related macular degeneration clinic: a prospective study

    OpenAIRE

    Muen, Wisam J; Hewick, Simon A

    2011-01-01

    Objectives To evaluate the quality of referrals to a neovascular age-related macular degeneration clinic from optometrists using the standard Rapid Access Referral Form (RARF) from the Royal College of Ophthalmologists. Design A prospective study. Prospective data were gathered from all optometry referrals using the RARF, between the periods of December 2006 to August 2009. These were assessed for accuracy of history, clinical signs and final diagnosis as compared to a macula expert. Setting ...

  18. Placental growth factor and its potential role in diabetic retinopathy and other ocular neovascular diseases.

    Science.gov (United States)

    Nguyen, Quan Dong; De Falco, Sandro; Behar-Cohen, Francine; Lam, Wai-Ching; Li, Xuri; Reichhart, Nadine; Ricci, Federico; Pluim, Jennifer; Li, William W

    2018-02-01

    The role of vascular endothelial growth factor (VEGF), including in retinal vascular diseases, has been well studied, and pharmacological blockade of VEGF is the gold standard of treatment for neovascular age-related macular degeneration, retinal vein occlusion and diabetic macular oedema. Placental growth factor (PGF, previously known as PlGF), a homologue of VEGF, is a multifunctional peptide associated with angiogenesis-dependent pathologies in the eye and non-ocular conditions. Animal studies using genetic modification and pharmacological treatment have demonstrated a mechanistic role for PGF in pathological angiogenesis. Inhibition decreases neovascularization and microvascular abnormalities across different models, including oxygen-induced retinopathy, laser-induced choroidal neovascularization and in diabetic mice exhibiting retinopathies. High levels of PGF have been found in the vitreous of patients with diabetic retinopathy. Despite these strong animal data, the exact role of PGF in pathological angiogenesis in retinal vascular diseases remains to be defined, and the benefits of PGF-specific inhibition in humans with retinal neovascular diseases and macular oedema remain controversial. Comparative effectiveness research studies in patients with diabetic retinal disease have shown that treatment that inhibits both VEGF and PGF may provide superior outcomes in certain patients compared with treatment that inhibits only VEGF. This review summarizes current knowledge of PGF, including its relationship to VEGF and its role in pathological angiogenesis in retinal diseases, and identifies some key unanswered questions about PGF that can serve as a pathway for future basic, translational and clinical research. © 2016 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation and European Association for Vision & Eye Research.

  19. Neovascularization Potential of Blood Outgrowth Endothelial Cells From Patients With Stable Ischemic Heart Failure Is Preserved

    OpenAIRE

    Dauwe, Dieter; Pelacho, Beatriz; Wibowo, Arief; Walravens, Ann-Sophie; Verdonck, Kristoff; Gillijns, Hilde; Caluwe, Ellen; Pokreisz, Peter; van Gastel, Nick; Carmeliet, Geert; Depypere, Maarten; Maes, Frederik; Vanden Driessche, Nina; Droogne, Walter; Van Cleemput, Johan

    2016-01-01

    Background Blood outgrowth endothelial cells (BOECs) mediate therapeutic neovascularization in experimental models, but outgrowth characteristics and functionality of BOECs from patients with ischemic cardiomyopathy (ICMP) are unknown. We compared outgrowth efficiency and in?vitro and in?vivo functionality of BOECs derived from ICMP with BOECs from age?matched (ACON) and healthy young (CON) controls. Methods and Results We isolated 3.6?0.6 BOEC colonies/100?106 mononuclear cells (MNCs) from 6...

  20. Gold nanoparticle enhancement of stereotactic radiosurgery for neovascular age-related macular degeneration

    Science.gov (United States)

    Ngwa, Wilfred; Makrigiorgos, G. Mike; Berbeco, Ross I.

    2012-10-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries for people over the age of 50. In this work, the dosimetric feasibility of using gold nanoparticles (AuNP) as radiosensitizers to enhance kilovoltage stereotactic radiosurgery for neovascular AMD is investigated. Microdosimetry calculations at the sub-cellular level were carried out to estimate the radiation dose enhancement to individual nuclei in neovascular AMD endothelial cells (nDEF) due to photon-induced photo-/Auger electrons from x-ray-irradiated AuNP. The nDEF represents the ratio of radiation doses to the endothelial cell nuclei with and without AuNP. The calculations were carried out for a range of feasible AuNP local concentrations using the clinically applicable 100 kVp x-ray beam parameters employed by a commercially available x-ray therapy system. The results revealed nDEF values of 1.30-3.26 for the investigated concentration range of 1-7 mg g-1, respectively. In comparison, for the same concentration range, nDEF values of 1.32-3.40, 1.31-3.33, 1.29-3.19, 1.28-3.12 were calculated for 80, 90, 110 and 120 kVp x-rays, respectively. Meanwhile, calculations as a function of distance from the AuNP showed that the dose enhancement, for 100 kVp, is markedly confined to the targeted neovascular AMD endothelial cells where AuNP are localized. These findings provide impetus for considering the application of AuNP to enhance therapeutic efficacy during stereotactic radiosurgery for neovascular AMD.

  1. Characteristics of choroidal neovascularization in the complications of age-related macular degeneration prevention trial.

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    Maguire, Maureen G; Alexander, Judith; Fine, Stuart L

    2008-09-01

    To describe the characteristics of incident choroidal neovascularization (CNV) in observed and treated eyes in the Complications of Age-related Macular Degeneration Prevention Trial (CAPT). Cross-sectional descriptive study within a multicenter, randomized clinical trial. Patients who developed CNV during CAPT follow-up. Inclusion criteria for CAPT specified bilateral large drusen (>or=10 drusen at least 125 micro), visual acuity >or=20/40 in each eye, and age >or=50. Exclusion criteria included CNV and geographic atrophy >1 Macular Photocoagulation Study (MPS) disc area or within 500 micro of the foveal center. One eye of each person was selected randomly for low-intensity laser treatment and the contralateral eye was observed. Fluorescein angiography was performed at baseline, annually for >or=5 years, and whenever there were symptoms of CNV. Trained readers at the CAPT Photograph Reading Center assessed color stereo photographs and angiogram negatives to identify CNV. Choroidal neovascularization was classified by type (predominantly classic CNV, minimally classic CNV, occult only CNV, or scar), location, and area. Visual acuity was measured by certified examiners. Symmetry of characteristics between eyes of bilaterally affected patients was examined. Choroidal neovascularization developed in 282 eyes of 225 patients. At the time of detection, 192 (68%) of the lesions were occult only, 153 (54%) were subfoveal, and 157 (56%) were or=20/40 in 123 (69%) of 179 eyes with visual acuity measured at the time of detection. Choroidal neovascularization developed in both eyes in 57 patients (25%) during CAPT follow-up. Lesions in eyes of bilaterally affected patients were no more similar to each other than affected eyes in 2 different patients. When patients are monitored closely, many CNV lesions can be detected outside of the fovea and when they are relatively small. Early detection may lead to improved long-term visual acuity.

  2. Clinical research of retinal laser photocoagulation and Ranibizumab on the treatment of neovascular glaucoma

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    Wei-Peng Jiang

    2015-10-01

    Full Text Available AIM: To explore the improvement of visual function and the adverse reactions of retinal laser photocoagulation combined with ranibizumab for the treatment of neovascular glaucoma(NVG, to provide the basis for clinical treatment.METHODS: One hundred patients with 129 eyes in our hospital from January 2012 to June 2014 were selected. They were randomly divided into the observation group and the control group, 50 cases in each one. Patients in the control group(67 eyeswere treated with retinal laser photocoagulation, and those in the observation group(62 eyeswere given retinal laser photocoagulation combined with ranibizumab treatment. After the treatment, the degeneration of iris neovascularization, visual acuity, intraocular pressure, ocular fundus and the adverse reactions were evaluated. Optical coherence tomography(OCTwas used to detect retinal nerve fiber layer(RNFLthickness and visual field defect. RESULTS: The degeneration rate of the iris neovascularization in the observation group was 95.2%(59/62, higher than that of the control group 83.6%(56/67(PPPPPP>0.05.CONCLUSION: The treatment of NVG with laser photocoagulation combined with ranibizumab has good clinical efficacy, and can significantly improve the vision and retinal structure and function of the patients, and is safer.

  3. Inhibition of erythropoietin siRNA on corneal neovascularization of rabbit

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    Yu-Shun Xue

    2017-03-01

    Full Text Available AIM: To observe the expression of erythropoietin(EPOon the corneal of rabbit and evaluate the inhibition effect of EPO siRNA on corneal neovascularization(CNV. METHODS: Totally 22 healthy rabbits were randomly divided into 2 groups, which were experimental group and normal control group. Both eyes of rabbits in experimental group were chosen to establish corneal neovascularization model by alkali burn. The morphologic change of corneal was observed with slit lamp microscope and the area of CNV was calculated every day. After alkali burn, the right eye of the experimental group was accepted EPO siRNA injection under the conjunctiva, and the left eye was assigned to be experimental control group. The corneal with CNV was collected for immunohistochemistry at 3d, 7d, 14d, 21d after alkali burn, and the expression of EPO was measured. RESULTS: CNV began growing at the 3d after alkali burn in experimental group, and it was vigorous growing at 7d-14d period. The result of immunohistochemistry shows that the expression of EPO increased after the operation. Compared with experimental group, the rabbits who were treated by EPO siRNA was found with less neovascularization on their corneal, and the expression of EPO decreased. There were statistical significance between the two group at different time(PCONCLUSION: EPO is likely to play an important role on CNV growth, and EPO siRNA can inhibit the growth of CNV by restraining the expression of EPO.

  4. The relationship between vascular endothelial dysfunction and treatment frequency in neovascular age-related macular degeneration.

    Science.gov (United States)

    Ueda-Consolvo, Tomoko; Hayashi, Atsushi; Ozaki, Mayumi; Nakamura, Tomoko; Yagou, Takaaki; Abe, Shinya

    2017-07-01

    To assess the correlation between endothelial dysfunction and frequency of antivascular endothelial growth factor (anti-VEGF) treatment for neovascular age-related macular degeneration (nAMD). We examined 64 consecutive patients with nAMD who were evaluated for endothelial function by use of peripheral arterial tonometry (EndoPAT 2000; Itamar Medical, Caesarea, Israel) at Toyama University Hospital from January 2015. We tallied the number of anti-VEGF treatments between January 2014 and December 2015 and determined the correlation between the number of anti-VEGF injections and endothelial function expressed as the reactive hyperemia index (RHI). Multiple regression analysis was also performed to identify the independent predictors of a larger number of injections. The mean number of anti-VEGF injections was 8.2 ± 3.3. The mean lnRHI was 0.47 ± 0.17. The lnRHI correlated with the number of anti-VEGF injections (r = -0.56; P = 0.030). The multiple regression analysis revealed that endothelial function, neovascular subtypes, and treatment regimens were associated with the number of injections. Endothelial dysfunction may affect the efficacy of anti-VEGF therapy. Neovascular subtypes may also predict a larger number of injections.

  5. Predictors of Visual Response to Intravitreal Bevacizumab for Treatment of Neovascular Age-Related Macular Degeneration

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    Kai Fang

    2013-01-01

    Full Text Available Purpose. To identify the predictors of visual response to the bevacizumab treatment of neovascular age-related macular degeneration (AMD. Design. A cohort study within the Neovascular AMD Treatment Trial Using Bevacizumab (NATTB. Methods. This was a multicenter trial including 144 participants from the NATTB study. Visual outcomes measured by change in visual acuity (VA score, proportion gaining ≥15 letters, and change in central retinal thickness (CRT were compared among groups according to the baseline, demographic, and ocular characteristics and genotypes. Results. Mean change in the VA score was 9.2 ± 2.3 SD letters with a total of 46 participants (31.9% gaining ≥15 letters. Change in median CRT was −81.5 μm. Younger age, lower baseline VA score, shorter duration of neovascular AMD, and TT genotype in rs10490924 were significantly associated with greater VA score improvement (P=0.028, P<0.001, P=0.02, and P=0.039, resp.. Lower baseline VA score and TT genotype in rs10490924 were significantly associated with a higher likelihood of gaining ≥15 letters (P=0.028, and P=0.021, resp.. Conclusions. Baseline VA and genotype of rs10490924 were both important predictors for visual response to bevacizumab at 6 months. This trial is registered with the Registration no. NCT01306591.

  6. Therapeutic Effects of Topical Netrin-4 Inhibits Corneal Neovascularization in Alkali-Burn Rats

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    Han, Yun; Shao, Yi; Liu, Tingting; Qu, Yang-Luowa; Li, Wei; Liu, Zuguo

    2015-01-01

    Netrins are secreted molecules involved in axon guidance and angiogenesis. However, the role of netrins in the vasculature remains unclear. Netrin-4 and netrin-1 have been found to be either pro- or antiangiogenic factors. Previously, we found that netrin-1 acts as an anti-angiogenic factor in rats by inhibiting alkali burn-induced corneal neovascularization. Here, we further investigate the effects of netrin-4, another member of the same netrin family, on neovascularization in vitro and in vivo. We found that netrin-4 functions similarly as netrin-1 in angiogenesis. In vitro angiogenesis assay shows that netrin-4 affected human umbilical vein endothelial cell (HUVEC) tube formation, viability and proliferation, apoptosis, migration, and invasion in a dose-dependent manner. Netrin-4 was topically applied in vivo to alkali-burned rat corneas on day 0 (immediately after injury) and/or day 10 post-injury. Netrin-4 subsequently suppressed and reversed corneal neovascularization. Netrin-4 inhibited corneal epithelial and stromal cell apoptosis, inhibited vascular endothelial growth factor (VEGF), but promoted pigment epithelium-derived factor (PEDF) expression, decreased NK-KB p65 expression, and inhibits neutrophil and macrophage infiltration. These results indicate that netrin-4 shed new light on its potential roles in treatmenting for angiogenic diseases that affect the ocular surface, as well as other tissues. PMID:25853509

  7. Physiologic ischaemic training induces endothelial progenitor cell mobilization and myocardial angiogenesis via endothelial nitric oxide synthase related pathway in rabbits.

    Science.gov (United States)

    Xiao, Mingyue; Lu, Xiao; Li, Jianan; Li, Ling; Li, Yongxue

    2014-04-01

    Ischaemia-induced angiogenesis promises to improve neovascularization by delivery of angiogenic factors or endothelial progenitor cells (EPCs) to cardiac ischaemic areas. In order to avoid the risk of excessive myocardial ischaemia, therefore, we hypothesized that physiological ischaemic training (PIT) of normal skeletal muscle might contribute to myocardial angiogenesis via nitric oxide mediated mobilization of EPCs from the bone marrow in the established rabbit model of controllable myocardial ischaemia. The rabbits were grouped by sham-operation, myocardial ischaemia without PIT, PIT and PIT with pretreatment with the endothelial nitric oxide synthase (eNOS) inhibitor L-nitroarginine methyl ester (L-NAME). Controlled myocardial ischaemia was modelled by a water balloon constrictor implanted on the left ventricular branch in a rabbit. The PIT procedure included three cycles of 3 min of cuff inflation followed by 5 min of deflation on hind limbs of the rabbits for 4 weeks. At the endpoints, circulating EPCs (CD34/Flk-1) were measured by fluorescence-activated cell sorter; capillary density, by immunohistochemistry; blood flow, by a microsphere technique; endothelial nitric oxide synthase (eNOS) mRNA and protein, by real-time reverse transcriptase (RT)-PCR and Western blotting. The mRNA levels of eNOS were significantly higher in the PIT and L-NAME groups than in the sham-operation group (P < 0.05). Phospho-eNOS protein expression was higher in the PIT group than in the sham-operation and myocardial ischaemia without PIT groups (P < 0.05), and the effect was inhibited by L-NAME pretreatment (P < 0.05). Compared with sham-operation and myocardial ischaemia without PIT groups, the PIT group had the highest EPC count (P < 0.001), and the increase of capillary density (P < 0.01) and collateral blood flow (P < 0.05) in the ischaemic myocardium was consistent with the finding of EPC count. These effects were also inhibited by pretreatment with

  8. Pinocembrin ex vivo preconditioning improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats.

    Science.gov (United States)

    Ahmed, Lamiaa A; Rizk, Sherine M; El-Maraghy, Shohda A

    2017-08-15

    Pulmonary hypertension is still not curable and the available current therapies can only alleviate symptoms without hindering the progression of disease. The present study was directed to investigate the possible modulatory effect of pinocembrin on endothelial progenitor cells transplanted in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60mg/kg). Endothelial progenitor cells were in vitro preconditioned with pinocembrin (25mg/L) for 30min before being i.v. injected into rats 2weeks after monocrotaline administration. Four weeks after monocrotaline administration, blood pressure, electrocardiography and right ventricular systolic pressure were recorded. Rats were sacrificed and serum was separated for determination of endothelin-1 and asymmetric dimethylarginine levels. Right ventricles and lungs were isolated for estimation of tumor necrosis factor-alpha and transforming growth factor-beta contents as well as caspase-3 activity. Moreover, protein expression of matrix metalloproteinase-9 and endothelial nitric oxide synthase in addition to myocardial connexin-43 was assessed. Finally, histological analysis of pulmonary arteries, cardiomyocyte cross-sectional area and right ventricular hypertrophy was performed and cryosections were done for estimation of cell homing. Preconditioning with pinocembrin provided a significant improvement in endothelial progenitor cells' effect towards reducing monocrotaline-induced elevation of inflammatory, fibrogenic and apoptotic markers. Furthermore, preconditioned cells induced a significant amelioration of endothelial markers and cell homing and prevented monocrotaline-induced changes in right ventricular function and histological analysis compared with native cells alone. In conclusion, pinocembrin significantly improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats

  9. THE AGES OF TYPE Ia SUPERNOVA PROGENITORS

    International Nuclear Information System (INIS)

    Brandt, Timothy D.; Aubourg, Eric; Strauss, Michael A.; Tojeiro, Rita; Heavens, Alan; Jimenez, Raul

    2010-01-01

    Using light curves and host galaxy spectra of 101 Type Ia supernovae (SNe Ia) with redshift z ∼ 2.4 Gyr. We find that each channel contributes roughly half of the Type Ia rate in our reference sample. We also construct the average spectra of high-stretch and low-stretch SN Ia host galaxies, and find that the difference of these spectra looks like a main-sequence B star with nebular emission lines indicative of star formation. This supports our finding that there are two populations of SNe Ia, and indicates that the progenitors of high-stretch supernovae are at the least associated with very recent star formation in the last few tens of Myr. Our results provide valuable constraints for models of Type Ia progenitors and may help improve the calibration of SNe Ia as standard candles.

  10. Interneuron progenitor transplantation to treat CNS dysfunction

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    Muhammad O Chohan

    2016-08-01

    Full Text Available Due to the inadequacy of endogenous repair mechanisms diseases of the nervous system remain a major challenge to scientists and clinicians. Stem cell based therapy is an exciting and viable strategy that has been shown to ameliorate or even reverse symptoms of CNS dysfunction in preclinical animal models. Of particular importance has been the use of GABAergic interneuron progenitors as a therapeutic strategy. Born in the neurogenic niches of the ventral telencephalon, interneuron progenitors retain their unique capacity to disperse, integrate and induce plasticity in adult host circuitries following transplantation. Here we discuss the potential of interneuron based transplantation strategies as it relates to CNS disease therapeutics. We also discuss mechanisms underlying their therapeutic efficacy and some of the challenges that face the field.

  11. Neural Progenitors Adopt Specific Identities by Directly Repressing All Alternative Progenitor Transcriptional Programs.

    Science.gov (United States)

    Kutejova, Eva; Sasai, Noriaki; Shah, Ankita; Gouti, Mina; Briscoe, James

    2016-03-21

    In the vertebrate neural tube, a morphogen-induced transcriptional network produces multiple molecularly distinct progenitor domains, each generating different neuronal subtypes. Using an in vitro differentiation system, we defined gene expression signatures of distinct progenitor populations and identified direct gene-regulatory inputs corresponding to locations of specific transcription factor binding. Combined with targeted perturbations of the network, this revealed a mechanism in which a progenitor identity is installed by active repression of the entire transcriptional programs of other neural progenitor fates. In the ventral neural tube, sonic hedgehog (Shh) signaling, together with broadly expressed transcriptional activators, concurrently activates the gene expression programs of several domains. The specific outcome is selected by repressive input provided by Shh-induced transcription factors that act as the key nodes in the network, enabling progenitors to adopt a single definitive identity from several initially permitted options. Together, the data suggest design principles relevant to many developing tissues. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Observational Investigations of the Progenitors of Supernovae

    Science.gov (United States)

    Lyman, J. D.

    2014-03-01

    Supernovae (SNe) are the spectacular deaths of stars and have shaped the universe we see today. Their far-reaching influence affects the chemical and dynamical evolution of galaxies, star formation, neutron star and black hole formation, and they are largely responsible for most of the heavy elements that make up the universe, including around 90 per cent of the reader. They also provide laboratories of nuclear and particle physics far beyond what we can construct on Earth and act as probes of extreme density and energy. This thesis presents new research into understanding the nature of the progenitor systems of various types of SNe, as well as presenting results that will allow their study to be more productive in the future, through use of automated pipelines and methods to increase the science value of discovered SNe. An environmental study of two peculiar types of transients ('Calcium-rich' and '2002cx-like'), which may not be true SNe, reveals extremely different ages of the exploding systems that will constrain the current theoretical effort into discovering the progenitor systems. The GRB-SN 120422A/2012bz is investigated and found to be an extremely luminous and energetic SN, even amongst the infamously bright GRB-SNe. A method is presented that allows an accurate reconstruction of the bolometric light curve of a core-collapse SN, which relies on only two optical filter observations - this will hugely reduce the observational cost of constructing bolometric light curves, a tool of great importance when hoping to constrain the nature of a SN explosion and hence its progenitor. Finally, this method is utilised to construct the largest bolometric CCSN bolometric light curve sample to date, and these are analytically modelled to reveal population statistics of the explosions, thus informing on the nature of the progenitors.

  13. Pegaptanib sodium treatment in neovascular age-related macular degeneration: clinical experience in Germany

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    Nikolaus Feucht

    2008-06-01

    Full Text Available Nikolaus Feucht, Huebner Matthias, Chris P Lohmann, Mathias MaierAugenklinik rechts der Isar, Technical University Munich, GermanyBackground: The VEGF Inhibition Study In Ocular Neovascularisation (VISION reported the efficacy of intravitreal (ITV vascular endothelial growth factor (VEGF inhibition with pegaptanib sodium (Macugen® for the treatment of neovascular age-related macular degeneration (AMD. This paper reports clinical experience with pegaptanib sodium for the treatment of occult or minimally classic choroidal neovascularization (CNV due to AMD.Material and methods: The study included 50 eyes (in 49 patients with either occult CNV or minimally classic CNV secondary to neovascular AMD who were not eligible for photodynamic therapy (PDT. Study data were analyzed retrospectively. During the 6-month study, patients were administered an average 2.74 injections of 0.3 mg ITV pegaptanib sodium. Angiography and optical coherence tomography (OCT examinations were carried out and intraocular pressure (IOP and visual acuity (VA were measured at baseline, at 3 months and at 6 months. An eye examination was performed and VA was measured the 2 days following treatment and then again at weeks 4–6, and at 3 and 6 months. OCT, VA, and IOP were also assessed at 1 month.Results: ITV pegaptanib sodium was well tolerated and no treatment complications arose. Mean VA was measured as: 0.37 ± 0.24 at baseline; 0.37 ± 0.25 at 1 month; 0.37 ± 0.25 at 3 months and 0.40 ± 0.26 at 6 months. VA was stabilized in approximately 90% of eyes treated with pegaptanib sodium. OCT examination showed a minimal change in central retinal thickness (CRT during the course of the study, from 251.19 µm at baseline to 251.63 µm at 6 months. No elevation in IOP was measured during treatment at 4–6 months in patients receiving pegaptanib sodium.Conclusions: ITV therapy with pegaptanib sodium for occult and minimally classic CNV secondary to neovascular AMD offered good

  14. EVOLUTION OF PROGENITORS FOR ELECTRON CAPTURE SUPERNOVAE

    International Nuclear Information System (INIS)

    Takahashi, Koh; Umeda, Hideyuki; Yoshida, Takashi

    2013-01-01

    We provide progenitor models for electron capture supernovae (ECSNe) with detailed evolutionary calculation. We include minor electron capture nuclei using a large nuclear reaction network with updated reaction rates. For electron capture, the Coulomb correction of rates is treated and the contribution from neutron-rich isotopes is taken into account in each nuclear statistical equilibrium (NSE) composition. We calculate the evolution of the most massive super asymptotic giant branch stars and show that these stars undergo off-center carbon burning and form ONe cores at the center. These cores become heavier up to the critical mass of 1.367 M ☉ and keep contracting even after the initiation of O+Ne deflagration. Inclusion of minor electron capture nuclei causes convective URCA cooling during the contraction phase, but the effect on the progenitor evolution is small. On the other hand, electron capture by neutron-rich isotopes in the NSE region has a more significant effect. We discuss the uniqueness of the critical core mass for ECSNe and the effect of wind mass loss on the plausibility of our models for ECSN progenitors.

  15. Preliminary study of rabbit model with corneal neovascularization after thermal burn under the constant temperature

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    Yong Jia

    2014-07-01

    Full Text Available AIM:To explore the suitable conditions in rapid model of corneal neovascularization(CNVafter thermal burn under different constant temperature in rabbit. METHODS: Total 45 New Zealand white rabbits were divided randomly into five groups(A, B, C, D, E. A groups: 100℃(n=10, B groups: 200℃(n=10, C groups: 300℃(n=10, D groups: 400℃(n=10, and E groups: control group(n=5. All left eyes of rabbits in A,B,C,D groups were induced corneal neovascularization by constant temperature burning device. The growth of CNV was observed by slit lamp microscope and the area of CNV were recorded on 4 th, 7 th, 14th, 30th days postoperatively. SPSS 19.0 statistical package was used for data analysis, and the data was recorded by mean±standard deviation. Comparison by analysis of variance was made by repeated measures in the area of neovascularization at each time point in groups. Statistical tests were considered significantly when P values were less than 0.05. RESULTS: On postoperative 4th, 7th, 14th, 30th days: no neovascularization was found after corneal thermal burn in A group, but only a few nebula left(n=2; the area of CNV were(9.16±1.45mm2,(37.73±5.49mm2,(62.44±7.54mm2,(40.28±7.39mm2 in B group respectively; and(11.45±1.04mm2,(44.51±4.64mm2,(66.13±4.13mm2,(43.04±2.33mm2 in C group respectively; and(13.23±0.86mm2,(47.26±4.59mm2,(67.57±4.56mm2,(45.59±4.44mm2 in D group respectively, and part corneal carbide(n=4was observed as well as corneal perforation(n=6were found on 3d in D group. No neovascularization was found in normal control group. Comparison of the areas of CNV at each time point between groups was statistically different, PPCOCLUSION: In 4 to 7d, the higher the temperature is, the more the neovascularization area of CNV are. It has no significant difference in 14 to 30d. But corneal carbide and corneal perforation are often found in 400℃ group, so its modeling failure rate is high. It is between 200℃ and 300℃ that

  16. Radiation therapy for ocular choroidal neovascularization (phase I/II study): preliminary report

    International Nuclear Information System (INIS)

    Sasai, Keisuke; Murata, Rumi; Mandai, Michiko; Takahashi, Masayo; Ogura, Yuichiro; Ngata, Yasushi; Nishimura, Yasumasa; Hiraoka, Masahiro

    1997-01-01

    Purpose/Objective: Choroidal neovascularization (CNV) is a major cause of severe loss of visual acuity in some ocular diseases such as age-related macular degeneration (ARMD) and angioid streaks. Laser photocoagulation has been used to treat patients with subfoveal neovascular lesions with well-demarcated boundaries. However, the treatment method is usually associated with a large decrease in visual acuity. Therefore, indications for this treatment are very limited. Recently, some investigators reported the effect of low dose irradiation on the sub retinal neovascular membranes in CNV. We conducted a Phase I/II study to determine the toxicity and efficacy of external photon beam radiotherapy in patients with CNV. Methods and Materials: Between April, 1994 and July, 1995, 36 patients with choroidal neovascularization (34 with ARMD and 2 with angioid streaks) were treated with radiation therapy. Treatment planning was performed using a CT simulator that enables real-time treatment planning from multiple CT slices. The clinical target volume that included the macula and optic disc received a dose of 10 Gy/5 fractions/1 week (first 18 eyes) or 20 Gy/10 fractions/2 weeks (last 18 eyes). All eyes were irradiated with a single lateral 6 MV photon beam, angled 10 degrees posteriorly to exclude the ipsilateral lens and the contralateral eye from the radiation field. The ipsilateral lens was irradiated with less than 10% of the total reference dose. The field size averaged 3.0 x 2.5 cm. Records of the 17 eyes with CNV referred to our hospital in 1993, which satisfied the eligibility criteria for this study, were retrospectively analyzed for comparison. Results: There was no significant acute morbidity. All patients were followed regularly by both ophthalmologists and radiation oncologists. Cataract formation after 1 year of the treatment was observed in one patient who had received a dose of 20 Gy. One patient who had received 20 Gy complained of transient dry-eye sensation

  17. Gene Therapy with Endogenous Inhibitors of Angiogenesis for Neovascular Age-Related Macular Degeneration: Beyond Anti-VEGF Therapy

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    Selwyn M. Prea

    2015-01-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of substantial and irreversible vision loss amongst elderly populations in industrialized countries. The advanced neovascular (or “wet” form of the disease is responsible for severe and aggressive loss of central vision. Current treatments aim to seal off leaky blood vessels via laser therapy or to suppress vessel leakage and neovascular growth through intraocular injections of antibodies that target vascular endothelial growth factor (VEGF. However, the long-term success of anti-VEGF therapy can be hampered by limitations such as low or variable efficacy, high frequency of administration (usually monthly, potentially serious side effects, and, most importantly, loss of efficacy with prolonged treatment. Gene transfer of endogenous antiangiogenic proteins is an alternative approach that has the potential to provide long-term suppression of neovascularization and/or excessive vascular leakage in the eye. Preclinical studies of gene transfer in a large animal model have provided impressive preliminary results with a number of transgenes. In addition, a clinical trial in patients suffering from advanced neovascular AMD has provided proof-of-concept for successful gene transfer. In this mini review, we summarize current theories pertaining to the application of gene therapy for neovascular AMD and the potential benefits when used in conjunction with endogenous antiangiogenic proteins.

  18. Radiation therapy for ocular choroidal neovascularization (phase I/II study)

    International Nuclear Information System (INIS)

    Sasai, Keisuke; Murata, Rumi; Mandai, Michiko; Takahashi, Masayo; Hiraoka, Masahiro

    1996-01-01

    Purpose/Objective: Choroidal neovascularization (CNV) is a major cause of severe loss of visual acuity in some ocular diseases such as age-related macular degeneration (ARMD) and angio-streaks. Laser photocoagulation has been used to treat patients with subfoveal neovascular lesions with well demarcated boundaries. However, the treatment method is usually associated with a large decrease in visual acuity. Therefore, indications for this treatment are very limited. Recently, some investigators reported the effect of low dose irradiation on the subretinal neovascular membranes in CNV. We conducted a phase I/II study to determine the toxicity and efficacy of external photon beam radiotherapy in patients with CNV. Materials and Methods: Between April 1994 and July 1995, 36 patients with choroidal neovascularization (34 with ARMD; 2 with angiostreaks) were treated with radiation therapy. Eligibility criteria for this study were as follows: the eyes had subretinal neovascular membranes in the avascular area of the fovea; the neovascular membranes had grown in size in the last 6 months; the best pretreatment corrected visual acuity was worse than (20(25)); there were no large subretinal hemorrhages causing decrease in visual acuity; patients were 50 years or older and had not received laser photocoagulation nor other treatment for this condition. Written informed consent was obtained from all patients. The patients underwent fluorescein angiographic evaluation and documentation of their neovascular disease prior to irradiation. Fluorescein angiography, measurement of the best corrected visual acuity, ophthalmoscopic and biomicroscopic examinations were performed at 1, 3, 6, and 12 months after treatment. Treatment planning was performed using a CT simulator which enables real-time treatment planning from multiple CT slices. The clinical target volume included the macula and optic disc, which received a dose of 10 Gy/5 fractions/1 week (first 18 eyes) or 20 Gy/10 fractions

  19. Tissue engineering of bladder using vascular endothelial growth factor gene-modified endothelial progenitor cells.

    Science.gov (United States)

    Chen, Bai-Song; Xie, Hua; Zhang, Sheng-Li; Geng, Hong-Quan; Zhou, Jun-Mei; Pan, Jun; Chen, Fang

    2011-12-01

    This study assessed the use of vascular endothelial growth factor (VEGF) gene-modified endothelial progenitor cells (EPCs) seeded onto bladder acellular matrix grafts (BAMGs), to enhance the blood supply in tissue-engineered bladders in a porcine model. Autologous porcine peripheral EPCs were isolated, cultured, expanded, characterized, and modified with the VEGF gene using an adenovirus vector. The expression of VEGF was examined using reverse transcriptase polymerase chain reaction (RT-PCR) and an enzyme-linked immunosorbent assay (ELISA). VEGF gene modified EPCs were seeded onto BAMG and cultured for 3 days before implantation into pigs for bladder tissue engineering. A partial bladder cystectomy was performed in 12 pigs. The experimental group (6 pigs) received VEGF gene-modified EPC-seeded BAMG. The control group (6 pigs) received BAMG without seeded EPCs. The resulting tissue-engineered bladders were subject to a general and histological analysis. Microvessel density (MVD) was assessed using immunohistochemistry. The ex vivo transfection efficiency of EPCs was greater than 60%-70% when concentrated adenovirus was used. The genetically modified cells expressed both VEGF and green fluorescent protein (GFP). Scanning electron microscopy (SEM) and Masson's trichrome staining of cross sections of the cultured cells seeded to BAMG showed cell attachment and proliferation on the surface of the BAMG. Histological examination revealed bladder regeneration in a time-dependent fashion. Significant increases in MVD were observed in the experimental group, in comparison with the control group. VEGF-modified EPCs significantly enhanced neovascularization, compared with BAMG alone. These results indicate that EPCs, combined with VEGF gene therapy, may be a suitable approach for increasing blood supply in the tissue engineering of bladders. Thus, a useful strategy to achieve a tissue-engineered bladder is indicated.

  20. Perianal implantation of bioengineered human internal anal sphincter constructs intrinsically innervated with human neural progenitor cells.

    Science.gov (United States)

    Raghavan, Shreya; Miyasaka, Eiichi A; Gilmont, Robert R; Somara, Sita; Teitelbaum, Daniel H; Bitar, Khalil N

    2014-04-01

    The internal anal sphincter (IAS) is a major contributing factor to pressure within the anal canal and is required for maintenance of rectoanal continence. IAS damage or weakening results in fecal incontinence. We have demonstrated that bioengineered, intrinsically innervated, human IAS tissue replacements possess key aspects of IAS physiology, such as the generation of spontaneous basal tone and contraction/relaxation in response to neurotransmitters. The objective of this study is to demonstrate the feasibility of implantation of bioengineered IAS constructs in the perianal region of athymic rats. Human IAS tissue constructs were bioengineered from isolated human IAS circular smooth muscle cells and human enteric neuronal progenitor cells. After maturation of the bioengineered constructs in culture, they were implanted operatively into the perianal region of athymic rats. Platelet-derived growth factor was delivered to the implanted constructs through a microosmotic pump. Implanted constructs were retrieved from the animals 4 weeks postimplantation. Animals tolerated the implantation well, and there were no early postoperative complications. Normal stooling was observed during the implantation period. At harvest, implanted constructs were adherent to the perirectal rat tissue and appeared healthy and pink. Immunohistochemical analysis revealed neovascularization. Implanted smooth muscle cells maintained contractile phenotype. Bioengineered constructs responded in vitro in a tissue chamber to neuronally evoked relaxation in response to electrical field stimulation and vasoactive intestinal peptide, indicating the preservation of neuronal networks. Our results indicate that bioengineered innervated IAS constructs can be used to augment IAS function in an animal model. This is a regenerative medicine based therapy for fecal incontinence that would directly address the dysfunction of the IAS muscle. Copyright © 2014 Mosby, Inc. All rights reserved.

  1. Endothelial progenitors encapsulated in bioartificial niches are insulated from systemic cytotoxicity and are angiogenesis competent.

    Science.gov (United States)

    Ratliff, B B; Ghaly, T; Brudnicki, P; Yasuda, K; Rajdev, M; Bank, M; Mares, J; Hatzopoulos, A K; Goligorsky, M S

    2010-07-01

    Intrinsic stem cells (SC) participate in tissue remodeling and regeneration in various diseases and following toxic insults. Failure of tissue regeneration is in part attributed to lack of SC protection from toxic stress of noxious stimuli, thus prompting intense research efforts to develop strategies for SC protection and functional preservation for in vivo delivery. One strategy is creation of artificial SC niches in an attempt to mimic the requirements of endogenous SC niches by generating scaffolds with properties of extracellular matrix. Here, we investigated the use of hyaluronic acid (HA) hydrogels as an artificial SC niche and examined regenerative capabilities of encapsulated embryonic endothelial progenitor cells (eEPC) in three different in vivo models. Hydrogel-encapsulated eEPC demonstrated improved resistance to toxic insult (adriamycin) in vitro, thus prompting in vivo studies. Implantation of HA hydrogels containing eEPC to mice with adriamycin nephropathy or renal ischemia resulted in eEPC mobilization to injured kidneys (and to a lesser extent to the spleen) and improvement of renal function, which was equal or superior to adoptively transferred EPC by intravenous infusion. In mice with hindlimb ischemia, EPC encapsulated in HA hydrogels dramatically accelerated the recovery of collateral circulation with the efficacy superior to intravenous infusion of EPC. In conclusion, HA hydrogels protect eEPC against adriamycin cytotoxicity and implantation of eEPC encapsulated in HA hydrogels supports renal regeneration in ischemic and cytotoxic (adriamycin) nephropathy and neovascularization of ischemic hindlimb, thus establishing their functional competence and superior capabilities to deliver stem cells stored in and released from this bioartificial niche.

  2. The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures

    Energy Technology Data Exchange (ETDEWEB)

    Ali, Haytham [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University (Egypt); Galal, Omima [Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University (Egypt); Urata, Yoshishige; Goto, Shinji; Guo, Chang-Ying; Luo, Lan [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Abdelrahim, Eman [Department of Medical Histology, Qena Faculty of Medicine, South Valley University (Egypt); Ono, Yusuke [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Mostafa, Emtethal [Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University (Egypt); Li, Tao-Sheng, E-mail: litaoshe@nagasaki-u.ac.jp [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

    2014-09-26

    Highlights: • Nicaraven mitigated the radiation-induced reduction of c-kit{sup +} stem cells. • Nicaraven enhanced the function of hematopoietic stem/progenitor cells. • Complex mechanisms involved in the protection of nicaraven to radiation injury. - Abstract: Nicaraven, a hydroxyl radical-specific scavenger has been demonstrated to attenuate radiation injury in hematopoietic stem cells with 5 Gy γ-ray exposures. We explored the effect and related mechanisms of nicaraven for protecting radiation injury induced by sequential exposures to a relatively lower dose γ-ray. C57BL/6 mice were given nicaraven or placebo within 30 min before exposure to 50 mGy γ-ray daily for 30 days in sequences (cumulative dose of 1.5 Gy). Mice were victimized 24 h after the last radiation exposure, and the number, function and oxidative stress of hematopoietic stem cells were quantitatively estimated. We also compared the gene expression in these purified stem cells from mice received nicaraven and placebo treatment. Nicaraven increased the number of c-kit{sup +} stem/progenitor cells in bone marrow and peripheral blood, with a recovery rate around 60–90% of age-matched non-irradiated healthy mice. The potency of colony forming from hematopoietic stem/progenitor cells as indicator of function was completely protected with nicaraven treatment. Furthermore, nicaraven treatment changed the expression of many genes associated to DNA repair, inflammatory response, and immunomodulation in c-kit{sup +} stem/progenitor cells. Nicaraven effectively protected against damages of hematopoietic stem/progenitor cells induced by sequential exposures to a relatively low dose radiation, via complex mechanisms.

  3. The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures

    International Nuclear Information System (INIS)

    Ali, Haytham; Galal, Omima; Urata, Yoshishige; Goto, Shinji; Guo, Chang-Ying; Luo, Lan; Abdelrahim, Eman; Ono, Yusuke; Mostafa, Emtethal; Li, Tao-Sheng

    2014-01-01

    Highlights: • Nicaraven mitigated the radiation-induced reduction of c-kit + stem cells. • Nicaraven enhanced the function of hematopoietic stem/progenitor cells. • Complex mechanisms involved in the protection of nicaraven to radiation injury. - Abstract: Nicaraven, a hydroxyl radical-specific scavenger has been demonstrated to attenuate radiation injury in hematopoietic stem cells with 5 Gy γ-ray exposures. We explored the effect and related mechanisms of nicaraven for protecting radiation injury induced by sequential exposures to a relatively lower dose γ-ray. C57BL/6 mice were given nicaraven or placebo within 30 min before exposure to 50 mGy γ-ray daily for 30 days in sequences (cumulative dose of 1.5 Gy). Mice were victimized 24 h after the last radiation exposure, and the number, function and oxidative stress of hematopoietic stem cells were quantitatively estimated. We also compared the gene expression in these purified stem cells from mice received nicaraven and placebo treatment. Nicaraven increased the number of c-kit + stem/progenitor cells in bone marrow and peripheral blood, with a recovery rate around 60–90% of age-matched non-irradiated healthy mice. The potency of colony forming from hematopoietic stem/progenitor cells as indicator of function was completely protected with nicaraven treatment. Furthermore, nicaraven treatment changed the expression of many genes associated to DNA repair, inflammatory response, and immunomodulation in c-kit + stem/progenitor cells. Nicaraven effectively protected against damages of hematopoietic stem/progenitor cells induced by sequential exposures to a relatively low dose radiation, via complex mechanisms

  4. Evaluation of the siRNA PF-04523655 versus ranibizumab for the treatment of neovascular age-related macular degeneration (MONET Study)

    DEFF Research Database (Denmark)

    Nguyen, Quan Dong; Schachar, Ronald A; Nduaka, Chudy I

    2012-01-01

    To evaluate the efficacy of different dosing paradigms of PF-04523655 (PF) versus ranibizumab (comparator) in subjects with neovascular age-related macular degeneration (AMD).......To evaluate the efficacy of different dosing paradigms of PF-04523655 (PF) versus ranibizumab (comparator) in subjects with neovascular age-related macular degeneration (AMD)....

  5. Preferential Hyperacuity Perimeter (PreView PHP) for detecting choroidal neovascularization study.

    Science.gov (United States)

    Alster, Yair; Bressler, Neil M; Bressler, Susan B; Brimacombe, Judith A; Crompton, R Michael; Duh, Yi-Jing; Gabel, Veit-Peter; Heier, Jeffrey S; Ip, Michael S; Loewenstein, Anat; Packo, Kirk H; Stur, Michael; Toaff, Techiya

    2005-10-01

    To assess the ability of the Preferential Hyperacuity Perimeter (PreView PHP; Carl Zeiss Meditec, Dublin, CA) to detect recent-onset choroidal neovascularization (CNV) resulting from age-related macular degeneration (AMD) and to differentiate it from an intermediate stage of AMD. Prospective, comparative, concurrent, nonrandomized, multicenter study. Eligible participants' study eyes had a corrected visual acuity of 20/160 or better and either untreated CNV from AMD diagnosed within the last 60 days or an intermediate stage of AMD. After obtaining consent, visual acuity with habitual correction, masked PHP testing, stereoscopic color fundus photography, and fluorescein angiography were performed. Photographs and angiograms were evaluated by graders masked to diagnosis and PHP results. The reading center's diagnosis determined if the patient was categorized as having intermediate AMD or neovascular AMD. A successful study outcome was defined a priori as a sensitivity of at least 80% and a specificity of at least 80%. Of 185 patients who gave consent to be enrolled, 11 (6%) had PHP results judged to be unreliable. An additional 52 were not included because they did not meet all eligibility criteria. Of the remaining 122 patients, 57 had an intermediate stage of AMD and 65 had neovascular AMD. The sensitivity to detect newly diagnosed CNV using PHP testing was 82% (95% confidence interval [CI], 70%-90%). The specificity to differentiate newly diagnosed CNV from the intermediate stage of AMD using PHP testing was 88% (95% CI, 76%-95%). Preferential Hyperacuity Perimeter testing can detect recent-onset CNV resulting from AMD and can differentiate it from an intermediate stage of AMD with high sensitivity and specificity. These data suggest that monitoring with PHP should detect most cases of CNV of recent onset with few false-positive results at a stage when treatment usually would be beneficial. Thus, this monitoring should be considered in the management of the

  6. Progression of retinal pigment epithelial atrophy in antiangiogenic therapy of neovascular age-related macular degeneration.

    Science.gov (United States)

    Schütze, Christopher; Wedl, Manuela; Baumann, Bernhard; Pircher, Michael; Hitzenberger, Christoph K; Schmidt-Erfurth, Ursula

    2015-06-01

    To monitor retinal pigment epithelial (RPE) atrophy progression during antiangiogenic therapy of neovascular age-related macular degeneration (AMD) over 2 years using polarization-sensitive optical coherence tomography (OCT). Prospective interventional case series. setting: Clinical practice. Thirty patients (31 eyes) with treatment-naïve neovascular AMD. Standard intravitreal therapy (0.5 mg ranibizumab) was administered monthly during the first year and pro re nata (PRN; as-needed) during the second year. Spectral-domain (SD) OCT and polarization-sensitive OCT (selectively imaging the RPE) examinations were performed at baseline and at 1, 3, 6, 12, and 24 months using a standardized protocol. RPE-related changes were evaluated using a semi-automated polarization-sensitive OCT segmentation algorithm and correlated with SD OCT and fundus autofluorescence (FAF) findings. RPE response, geographic atrophy (GA) progression. Atrophic RPE changes included RPE thinning, RPE porosity, focal RPE atrophy, and development of GA. Early RPE loss (ie, RPE porosity, focal atrophy) increased progressively during initial monthly treatment and remained stable during subsequent PRN-based therapy. GA developed in 61% of eyes at month 24. Mean GA area increased from 0.77 mm(2) at 12 months to 1.10 mm(2) (standard deviation = 1.09 mm(2)) at 24 months. Reactive accumulation of RPE-related material at the lesion borders increased until month 3 and subsequently decreased. Progressive RPE atrophy and GA developed in the majority of eyes. RPE migration signifies certain RPE plasticity. Polarization-sensitive OCT specifically images RPE-related changes in neovascular AMD, contrary to conventional imaging methods. Polarization-sensitive OCT allows for precisely monitoring the sequence of RPE-related morphologic changes. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  7. A value-based medicine comparison of interventions for subfoveal neovascular macular degeneration.

    Science.gov (United States)

    Brown, Gary C; Brown, Melissa M; Brown, Heidi C; Kindermann, Sylvia; Sharma, Sanjay

    2007-06-01

    To perform a value-based medicine analysis of clinical trials that evaluate the interventions of laser photocoagulation, intravitreal pegaptanib therapy, and photodynamic therapy (PDT) with verteporfin for the treatment of classic subfoveal choroidal neovascularization. Reference case cost-utility analysis using value-based medicine principles, which use patient-based utility values and standardized, input variable criteria. Data from participants in the Macular Photocoagulation Study, Pegaptanib for Neovascular Age-Related Macular Degeneration Study, and the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy Study. Visual data were converted to a value-based format using time tradeoff utility analysis values from patients with macular degeneration. Costs were obtained from 2005 Medicare data. Outcomes (quality-adjusted life-years [QALYs]) and costs were discounted at a 3% annual rate. Interventional QALYs gained, percent improvement in quality of life, and dollars spent per QALY gained. Laser photocoagulation confers a 4.4% (P = 0.03 versus pegaptanib therapy) improvement in quality of life for the reference case, whereas pegaptanib therapy confers a 5.9% improvement and PDT confers an 8.1% (P = 0.0002 versus pegaptanib therapy) improvement. The cost-utility associated with laser photocoagulation is $8179, that for pegaptanib therapy is $66978, and that for PDT is $31544. All sensitivity analyses remain within the conventional standards of cost-effectiveness. Photodynamic therapy confers greater patient value than intravitreal pegaptanib therapy and laser photocoagulation for the treatment of classic subfoveal choroidal neovascularization. Despite the fact that laser photocoagulation is the most cost-effective intervention, both PDT and pegaptanib therapy deliver greater value, and thus are both preferred over laser photocoagulation. Using an economic measure, photodynamic therapy is the preferred treatment among these 3 interventions.

  8. VEGF-production by CCR2-dependent macrophages contributes to laser-induced choroidal neovascularization.

    Directory of Open Access Journals (Sweden)

    Torsten A Krause

    Full Text Available Age-related macular degeneration (AMD is the most prevalent cause of blindness in the elderly, and its exsudative subtype critically depends on local production of vascular endothelial growth factor A (VEGF. Mononuclear phagocytes, such as macrophages and microglia cells, can produce VEGF. Their precursors, for example monocytes, can be recruited to sites of inflammation by the chemokine receptor CCR2, and this has been proposed to be important in AMD. To investigate the role of macrophages and CCR2 in AMD, we studied intracellular VEGF content in a laser-induced murine model of choroidal neovascularisation. To this end, we established a technique to quantify the VEGF content in cell subsets from the laser-treated retina and choroid separately. 3 days after laser, macrophage numbers and their VEGF content were substantially elevated in the choroid. Macrophage accumulation was CCR2-dependent, indicating recruitment from the circulation. In the retina, microglia cells were the main VEGF+ phagocyte type. A greater proportion of microglia cells contained VEGF after laser, and this was CCR2-independent. On day 6, VEGF-expressing macrophage numbers had already declined, whereas numbers of VEGF+ microglia cells remained increased. Other sources of VEGF detectable by flow cytometry included in dendritic cells and endothelial cells in both retina and choroid, and Müller cells/astrocytes in the retina. However, their VEGF content was not increased after laser. When we analyzed flatmounts of laser-treated eyes, CCR2-deficient mice showed reduced neovascular areas after 2 weeks, but this difference was not evident 3 weeks after laser. In summary, CCR2-dependent influx of macrophages causes a transient VEGF increase in the choroid. However, macrophages augmented choroidal neovascularization only initially, presumably because VEGF production by CCR2-independent eye cells prevailed at later time points. These findings identify macrophages as a relevant source

  9. Neovascularity in patellar tendinopathy and the response to eccentric training: a case report using Power Doppler ultrasound.

    Science.gov (United States)

    McCreesh, Karen M; Riley, Sara J; Crotty, James M

    2013-12-01

    This report describes the case of an amateur soccer player with chronic patellar tendinopathy who underwent ultrasound imaging before and after engaging in an 8-week programme of eccentric exercise. On initial assessment, greyscale ultrasound imaging demonstrated tendon thickening and reduced echogenicity, while Power Doppler imaging demonstrated a large amount of neovascularity. After 8 weeks of an eccentric loading programme, the patient reported significantly improved symptoms and functional scores, while follow-up imaging demonstrated improvement in the echo appearance of the tendon and complete resolution of the neovascularity. The association between neovascularity and symptoms in tendinopathy research is conflicting, with a paucity of research in the area of patellar tendinopathy. While further research is needed to clarify the significance of greyscale and Power Doppler ultrasound changes in relation to symptoms in patellar tendinopathy, ultrasound imaging was shown to be a useful adjunct to diagnosis and outcome assessment in this case. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. A Chinese 2-herb formula (NF3) promotes hindlimb ischemia-induced neovascularization and wound healing of diabetic rats.

    Science.gov (United States)

    Tam, Jacqueline Chor-Wing; Ko, Chun-Hay; Lau, Kit-Man; To, Ming-Ho; Kwok, Hin-Fai; Chan, Yuet-Wa; Siu, Wing-Sum; Etienne-Selloum, Nelly; Lau, Ching-Po; Chan, Wai-Yee; Leung, Ping-Chung; Fung, Kwok-Pui; Schini-Kerth, Valérie B; Lau, Clara Bik-San

    2014-01-01

    Diabetic foot ulcer is closely associated with peripheral vascular disease. Enhancement of tissue oxidative stress, reduction of nitric oxide (NO) and angiogenic growth factors, and abnormal matrix metalloproteinase (MMP) activity are pathophysiological factors in post-ischemic neovascularization and diabetic wound healing. Our previous study demonstrated that the Chinese 2-herb formula, NF3, showed significant wound healing effects on diabetic foot ulcer rats. A novel rat diabetic foot ulcer with hindlimb ischemia model was established in order to strengthen our claims on the diabetic wound healing and post-ischemic neovascularization effects of NF3. Our results demonstrate that NF3 can significantly reduce the wound area of the diabetic foot ulcer rat with hindlimb ischemia by 21.6% (phealing and post-ischemic neovascularization in diabetes. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Increased Expression of CD200 on Circulating CD11b+ Monocytes in Patients with Neovascular Age-related Macular Degeneration

    DEFF Research Database (Denmark)

    Singh, Amardeep; Falk, Mads K; Hviid, Thomas V F

    2013-01-01

    OBJECTIVE: Dysregulation of retinal microglial activity has been implicated in the pathogenesis of neovascular age-related macular degeneration. Microglia activity can be regulated through the membrane protein CD200 and its corresponding receptor, the CD200 receptor (CD200R). Because both...... with neovascular age-related macular degeneration (AMD) and 44 age-matched controls without AMD. METHODS: The participants were aged 60 years or older, had no history of immune dysfunction or cancer, and were not receiving immune-modulating therapy. All participants were subjected to a structured interview......: Patients with neovascular AMD had a higher percentage of CD11b+CD200+ monocytes and CD200+ monocytes compared with controls. Multiple regression analysis revealed that the intergroup differences observed were independent of age. Moreover, an age-related increment in CD200 expression on monocytes...

  12. MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells.

    Science.gov (United States)

    Sánchez-Cid, Lourdes; Pons, Mònica; Lozano, Juan José; Rubio, Nuria; Guerra-Rebollo, Marta; Soriano, Aroa; Paris-Coderch, Laia; Segura, Miquel F; Fueyo, Raquel; Arguimbau, Judit; Zodda, Erika; Bermudo, Raquel; Alonso, Immaculada; Caparrós, Xavier; Cascante, Marta; Rafii, Arash; Kang, Yibin; Martínez-Balbás, Marian; Weiss, Stephen J; Blanco, Jerónimo; Muñoz, Montserrat; Fernández, Pedro L; Thomson, Timothy M

    2017-10-13

    MicroRNAs are critical regulators of gene networks in normal and abnormal biological processes. Focusing on invasive ductal breast cancer (IDC), we have found dysregulated expression in tumor samples of several microRNAs, including the miR-200 family, along progression from primary tumors to distant metastases, further reflected in higher blood levels of miR-200b and miR-7 in IDC patients with regional or distant metastases relative to patients with primary node-negative tumors. Forced expression of miR-200s in MCF10CA1h mammary cells induced an enhanced epithelial program, aldehyde dehydrogenase (ALDH) activity, mammosphere growth and ability to form branched tubuloalveolar structures while promoting orthotopic tumor growth and lung colonization in vivo . MiR-200s also induced the constitutive activation of the PI3K-Akt signaling through downregulation of PTEN, and the enhanced mammosphere growth and ALDH activity induced in MCF10CA1h cells by miR-200s required the activation of this signaling pathway. Interestingly, the morphology of tumors formed in vivo by cells expressing miR-200s was reminiscent of metaplastic breast cancer (MBC). Indeed, the epithelial components of MBC samples expressed significantly higher levels of miR-200s than their mesenchymal components and displayed a marker profile compatible with luminal progenitor cells. We propose that microRNAs of the miR-200 family promote traits of highly proliferative breast luminal progenitor cells, thereby exacerbating the growth and metastatic properties of transformed mammary epithelial cells.

  13. Decellularized matrix from tumorigenic human mesenchymal stem cells promotes neovascularization with galectin-1 dependent endothelial interaction

    DEFF Research Database (Denmark)

    Burns, Jorge S; Kristiansen, Malthe; Kristensen, Lars P

    2011-01-01

    . Histological analysis showed that cells of the most vascularized tumorigenic clone, -BD11 had a pericyte-like alpha smooth muscle actin (ASMA+) and CD146+ positive phenotype. Upon serum withdrawal in culture, -BD11 cells formed cord-like structures mimicking capillary morphogenesis. In contrast, cells...... of the poorly tumorigenic clone, -BC8 did not stain for ASMA, tumours were less vascularized and serum withdrawal in culture led to cell death. By exploring the heterogeneity in hMSC-TERT20 clones we aimed to understand molecular mechanisms by which mesenchymal stem cells may promote neovascularization....

  14. Surgical choroidal neovascular membrane removal in the era of anti-vascular endothelial growth factor agents

    Directory of Open Access Journals (Sweden)

    Nagpal Manish

    2009-01-01

    Full Text Available Intravitreal anti-vascular endothelial growth factor (VEGF agents have obtained acceptance as the mainstay in the management strategy of subfoveal choroidal neovascular membranes (CNVM due to varying etiologies. Few drawbacks include need for repeated intravitreal injections, with its adjunct risks, and the lack of a predefined treatment end point, which can cause doubts and uncertainty in the mind of the patient. Furthermore, it remains a significant financial burden for the patient. Herein we report our data of three patients who were reluctant for further re-injections of anti-VEGF agents and were therefore offered surgical removal of the CNVM by submacular surgery as an alternative treatment plan.

  15. Ranibizumab in neovascular age-related macular degeneration: a 5-year follow-up

    Directory of Open Access Journals (Sweden)

    Cvetkova NP

    2016-06-01

    Full Text Available Nadezhda P Cvetkova, Kristina Hölldobler, Philipp Prahs, Viola Radeck, Horst Helbig, David Märker Department of Ophthalmology, University of Regensburg, Regensburg, Germany Purpose: Our aim was to evaluate an optical coherence tomography (OCT and visual acuity (VA-guided, variable-dosing regimen with intravitreal ranibizumab injection for treating patients with neovascular age-related macular degeneration (AMD from 2007 to 2012. Design: This was a retrospective clinical study of 5 years follow-up in a tertiary eye center. Patients and methods: In this study, 66 patients with neovascular AMD (mean age of 74 years, SD 8.7 years were included. We investigated the development of best-corrected visual acuity (BCVA, the number of intravitreal injections, and the central retinal thickness measured with OCT (OCT Spectralis over 5 years of intravitreal treatment. Results: The mean number of intravitreal ranibizumab injections over 5 years was 8.8. The mean BCVA before therapy was 0.4 logarithm of the minimum angle of resolution (logMAR. After 5 years of therapy, the mean BCVA was 0.6 logMAR. In all, 16% of treated patients had stable VA over 5 years and 10% of study eyes approved their VA. The mean OCT-measured central retinal thickness at the beginning of this study was 295 µm; after 5 years of treatment, the mean central retinal thickness was 315 µm. There was an increase in central retinal thickness in 47.5% of examined eyes. Conclusion: Other studies showed VA improvement in OCT-guided variable-dosing regimens. Our study revealed a moderate decrease in VA after a total mean injection number as low as 8.8 injections over 5 years. In OCT, an increase in central retinal thickness over 5 years could be observed. Probably, this is due to deficient treatment when comparing the total injection number to other treatment regimens. Anti-VEGF therapy helps to keep the VA stable for a period of time, but cannot totally stop the progression of

  16. Treatment of age-related subfoveal choroidal neovascularization by low-dose external radiation. A preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Harino, Seiyo; Oshima, Yusuke; Tsujikawa, Kaoru; Oh, Ami; Sugimoto, Kiyoshi [Yodogawa Christian Hospital, Osaka (Japan); Murayama, Shigeyuki; Inoue, Toshihiko

    1997-04-01

    We applied low dose external beam radiation (6MV) to 17 eyes of 17 patients (Mean age 70.9 years, range 58-85) who had subfoveal choroidal neovascularization associated with age-related macular degeneration. None of the cases were suitable for photocoagulation according to the Macular Photo-coagulation Study protocol, and no feeding vessels underlying choroidal neovascular membrane could be detected. Corrected visual acuity ranged from 0.02 to 0.6 before treatment. The patients were divided into two groups. One group of 11 eyes was treated with 10 Gy and the other group of 6 eyes with 21 Gy. Mean follow up period was 347{+-}89 (mean{+-}standard deviation) days in the 10 Gy group and 312{+-}100 days in the 21 Gy group. We evaluated the outcome as `effective` if no progression in neovascular membrane was found by ophthalmoscopic and angiographic examination. Only 3 eyes (21%) of patients in the 10 Gy group and 2 eyes (33%) in 21 Gy group showed any effect. Although the rate of progression in choroidal neovascular membrane was significantly smaller in the 10 and 21 Gy group than in the controls, the corrected visual acuity in the treated group was not improved over that of the controls. No serious complications were seen. Only one case showed a stabilized neovascular membrane in the control group of 7 patients. Although the present results seem to be worse than those in previous reports, the efficacy of this treatment still needs to be evaluated because no beneficial strategies in the treatment of subfoveal neovascularization have been established. (author)

  17. Strategies for improving early detection and diagnosis of neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Keane PA

    2015-02-01

    Full Text Available Pearse A Keane,1 Gabriella de Salvo,2 Dawn A Sim,1 Srini Goverdhan,2 Rupesh Agrawal,1 Adnan Tufail1 1NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, 2Department of Ophthalmology, University Hospital Southampton NHS Foundation Trust, Southampton, UK Abstract: Treatment of the neovascular form of age-related macular degeneration (AMD has been revolutionized by the introduction of such agents as ranibizumab, bevacizumab, and aflibercept. As a result, the incidence of legal blindness occurring secondary to AMD has fallen dramatically in recent years in many countries. While these agents have undoubtedly been successful in reducing visual impairment and blindness, patients with neovascular AMD typically lose some vision over time, and often lose the ability to read, drive, or perform other important activities of daily living. Efforts are therefore under way to develop strategies that allow for earlier detection and treatment of this disease. In this review, we begin by providing an overview of the rationale for, and the benefits of, early detection and treatment of neovascular AMD. To achieve this, we begin by providing an overview of the pathophysiology and natural history of choroidal neovascularization, before reviewing the evidence from both clinical trials and “real-world” outcome studies. We continue by highlighting an area that is often overlooked: the importance of patient education and awareness for early AMD detection. We conclude the review by reviewing an array of both established and emerging technologies for early detection of choroidal neovascularization, ranging from Amsler chart testing, to hyperacuity testing, to advanced imaging techniques, such as optical coherence tomography. Keywords: Amsler, detection, choroidal neovascularization, hyperacuity, optical coherence tomography

  18. Fibroblast Growth Factor-9 Activates c-Kit Progenitor Cells and Enhances Angiogenesis in the Infarcted Diabetic Heart

    Directory of Open Access Journals (Sweden)

    Dinender Singla

    2016-01-01

    Full Text Available We hypothesized that fibroblast growth factor-9 (FGF-9 would enhance angiogenesis via activating c-kit positive stem cells in the infarcted nondiabetic and diabetic heart. In brief, animals were divided into three groups: Sham, MI, and MI+FGF-9. Two weeks following MI or sham surgery, our data suggest that treatment with FGF-9 significantly diminished vascular apoptosis compared to the MI group in both C57BL/6 and db/db mice (p<0.05. Additionally, the number of c-kit+ve/SM α-actin+ve cells and c-kit+ve/CD31+ve cells were greatly enhanced in the MI+FGF-9 groups relative to the MI suggesting FGF-9 enhances c-Kit cell activation and their differentiation into vascular smooth muscle cells and endothelial cells, respectively (p<0.05. Histology shows that the total number of vessels were quantified for all groups and our data suggest that the FGF-9 treated groups had significantly more vessels than their MI counterparts (p<0.05. Finally, echocardiographic data suggests a significant improvement in left ventricular output, as indicated by fractional shortening and ejection fraction in both nondiabetic and diabetic animals treated with FGF-9 (p<0.05. Overall, our data suggests FGF-9 has the potential to attenuate vascular cell apoptosis, activate c-Kit progenitor cells, and enhance angiogenesis and neovascularization in C57BL/6 and db/db mice leading to improved cardiac function.

  19. Exercise training-induced different improvement profile of endothelial progenitor cells function in mice with or without myocardial infarction.

    Science.gov (United States)

    Guo, Yuan; Peng, Ran; Liu, Qiong; Xu, Danyan

    2016-10-15

    Neovascularization in response to ischemia after myocardial infarction (MI) has been widely considered as being initiated by endothelial progenitor cells (EPCs). Well-documented evidences in recent years have proved exercise training (ET) improving EPC function. However, whether ET-induced improvement of EPC function under or without ischemic state is different has not been reported. Mice performed ET following an exercise prescription 1week after MI or non-MI surgery respectively. Bone marrow-derived EPCs were isolated at 0day, 3days, 1week, 2weeks, 4weeks, and 8weeks of ET. After 7days cultivation, EPC functions including proliferation, adhesion, migration, and in vitro angiogenesis were measured. AKT/glycogen synthase kinase 3β (GSK3β) signaling pathway was tested by western blotting. EPC function in mice underwent non-MI surgery was attenuated overtime, while ET ameliorated this tendency. EPC function was peaked at 4weeks ET in non-MI surgery mice and maintained with an extended exercise time. Besides, simple ischemia was sufficient to enhanced EPC function, with a maximum at 2weeks of MI surgery. In MI mice, ET further improved EPC function and achieved peak at 2weeks exercise. Furthermore, AKT/GSK3β signaling pathway activation was consistent with EPC function change after ischemia, which was further promoted by 4weeks exercise. ET significantly increased EPC function in mice both with and without MI, but the time points of peak function were different. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Retinal progenitor cell xenografts to the pig retina

    DEFF Research Database (Denmark)

    Warfvinge, Karin; Kiilgaard, Jens Folke; Lavik, Erin B

    2005-01-01

    To investigate the survival, integration, and differentiation of mouse retinal progenitor cells after transplantation to the subretinal space of adult pigs.......To investigate the survival, integration, and differentiation of mouse retinal progenitor cells after transplantation to the subretinal space of adult pigs....

  1. Selective uptake of boronophenylalanine by glioma stem/progenitor cells

    International Nuclear Information System (INIS)

    Sun, Ting; Zhou, Youxin; Xie, Xueshun; Chen, Guilin; Li, Bin; Wei, Yongxin; Chen, Jinming; Huang, Qiang; Du, Ziwei

    2012-01-01

    The success of boron neutron capture therapy (BNCT) depends on the amount of boron in cells and the tumor/blood and tumor/(normal tissue) boron concentration ratios. For the first time, measurements of boron uptake in both stem/progenitor and differentiated glioma cells were performed along with measurements of boron biodistribution in suitable animal models. In glioma stem/progenitor cells, the selective accumulation of boronophenylalanine (BPA) was lower, and retention of boron after BPA removal was longer than in differentiated glioma cells in vitro. However, boron biodistribution was not statistically significantly different in mice with xenografts. - Highlights: ► Uptake of BPA was analyzed in stem/progenitor and differentiated glioma cells. ► Selective accumulation of BPA was lower in glioma stem/progenitor cells. ► Retention of boron after BPA removal was longer in glioma stem/progenitor cells. ► Boron biodistribution was not statistically different in mice with xenografts.

  2. Impairment of circulating endothelial progenitors in Down syndrome

    Directory of Open Access Journals (Sweden)

    Costa Valerio

    2010-09-01

    Full Text Available Abstract Background Pathological angiogenesis represents a critical issue in the progression of many diseases. Down syndrome is postulated to be a systemic anti-angiogenesis disease model, possibly due to increased expression of anti-angiogenic regulators on chromosome 21. The aim of our study was to elucidate some features of circulating endothelial progenitor cells in the context of this syndrome. Methods Circulating endothelial progenitors of Down syndrome affected individuals were isolated, in vitro cultured and analyzed by confocal and transmission electron microscopy. ELISA was performed to measure SDF-1α plasma levels in Down syndrome and euploid individuals. Moreover, qRT-PCR was used to quantify expression levels of CXCL12 gene and of its receptor in progenitor cells. The functional impairment of Down progenitors was evaluated through their susceptibility to hydroperoxide-induced oxidative stress with BODIPY assay and the major vulnerability to the infection with human pathogens. The differential expression of crucial genes in Down progenitor cells was evaluated by microarray analysis. Results We detected a marked decrease of progenitors' number in young Down individuals compared to euploid, cell size increase and some major detrimental morphological changes. Moreover, Down syndrome patients also exhibited decreased SDF-1α plasma levels and their progenitors had a reduced expression of SDF-1α encoding gene and of its membrane receptor. We further demonstrated that their progenitor cells are more susceptible to hydroperoxide-induced oxidative stress and infection with Bartonella henselae. Further, we observed that most of the differentially expressed genes belong to angiogenesis, immune response and inflammation pathways, and that infected progenitors with trisomy 21 have a more pronounced perturbation of immune response genes than infected euploid cells. Conclusions Our data provide evidences for a reduced number and altered

  3. Role of optical coherence tomography angiography in myopic choroidal neovascularization after intravitreal injections of Ranibizumab

    Directory of Open Access Journals (Sweden)

    Meng Cai

    2017-10-01

    Full Text Available AIM: To investigate the change of myopic choroidal neovascularization treated by ranibizumab and evaluate their value in monitoring the effect of anti- vascular endothelial growth factor(VEGFtherapy.METHODS: The study enrolled 30 patients(30 eyesdiagnosed with myopic choroidal neovascularization. All affected eyes were treated with intravitreal ranibizumab 0.05mL(10mg/mL. Best corrected visual acuity(BCVA, non-contact tonometer, ophthalmoscope, fundus fluorescein angiograph(FFAand OCTA were evaluated monthly until 6mo. The changes of BCVA and central macular thickness(CMTwere compared at 1, 3 and 6mo after treatment.RESULTS: All patients received an average of 1.70±0.65 injections. BCVA was 0.96±0.17(LogMARbefore therapy, and BCVA 1, 3 and 6mo after treatment respectively improved by 0.23±0.09, 0.34±0.07, 0.38±0.11. The differences were significant(t=5.461, 8.191, 8.894; Pt=12.007, 13.360, 9.531; PCONCLUSION: Intravitreal ranibizumab for CNV secondary to pathologic myopia is effective and safe; OCTA is a noninvasive and time-saving new technology, and it also is a promising tool for clinicians to make preliminary diagnosis and assess treatment efficacy in the follow-up visits.

  4. Posterior capsule opacification and neovascularization treated with intravitreal bevacizumab and Nd:YAG capsulotomy

    Directory of Open Access Journals (Sweden)

    Grimelda Yuriana Sánchez-Castro

    2008-10-01

    Full Text Available Grimelda Yuriana Sánchez-Castro1, Alejandra Hitos-Fájer1, Erick Mendoza-Schuster1, Raul Velez-Montoya2, Cecilio Francisco Velasco-Barona11Asociación para Evitar la Ceguera en México. Hospital “Dr. Luis Sánchez Bulnes”, México, D.F. Ophthalmology Department – Anterior Segment; 2Asociación para Evitar la Ceguera en México. Hospital “Dr. Luis Sánchez Bulnes”, México, D.F. Ophthalmology Department – Retina departmentAbstract: We reported a 75-year-old diabetic man, who developed opacification and neovascularization of the posterior capsule after extracapsular cataract extraction and posterior chamber intraocular lens implantation. The patient was treated with two injections of 2.5 mg of intravitreal bevacizumab. The treatment produced an important regression of the posterior capsular new vessels, allowing us to perform a successful Nd:YAG capsulotomy, clearing the visual axis and improving the visualization of the posterior pole. Even though, best corrected visual acuity was 20/200 due to diabetic macular edema.Keywords: posterior capsule opacification, posterior capsule neovascularization, cataract surgery, postoperative complications, intravitreal bevacizumab

  5. Gemcitabine-induced CXCL8 expression counteracts its actions by inducing tumor neovascularization

    International Nuclear Information System (INIS)

    Song, Yao; Baba, Tomohisa; Li, Ying-Yi; Furukawa, Kaoru; Tanabe, Yamato; Matsugo, Seiichi; Sasaki, Soichiro; Mukaida, Naofumi

    2015-01-01

    Patients with pancreatic ductal adenocarcinoma (PDAC) are frequently complicated with metastatic disease or locally advanced tumors, and consequently need chemotherapy. Gemcitabine is commonly used for PDAC treatment, but with limited efficacy. The capacity of gemcitabine to generate reactive oxygen species (ROS) in human pancreatic cancer cells, prompted us to examine its effects on the expression of pro-inflammatory cytokines and chemokines. We observed that gemcitabine enhanced selectively the expression of CXCL8 in human pancreatic cancer cells through ROS generation and NF-κB activation. In vitro blocking of CXCL8 failed to modulate gemcitabine-mediated inhibition of cell proliferation in human pancreatic cancer cells. Gemcitabine also enhanced CXCL8 expression in pancreatic cancer cells in xenografted tumor tissues. Moreover, anti-CXCL8 antibody treatment in vivo attenuated tumor formation as well as intra-tumoral vascularity in nude mice, which were transplanted with Miapaca-2 cells and treated with gemcitabine. Thus, gemcitabine-induced CXCL8 may counteract the drug through inducing neovascularization. - Highlights: • Gemcitabine induced CXCL8 expression in human pancreatic cancer cells. • CXCL8 expression required ROS generation and NF-κB activation. • CXCL8 did not affect in vitro proliferation of human pancreatic cancer cells. • CXCL8 in vivo counteracted gemcitabine by inducing neovascularization

  6. Surgical Outcome of Ahmed Valve Implantation in Mexican Patients with Neovascular Glaucoma.

    Science.gov (United States)

    Hernandez-Oteyza, Alejandra; Lazcano-Gomez, Gabriel; Jimenez-Roman, Jesus; Hernandez-Garciadiego, Carlos

    2014-01-01

    To describe clinical results of Ahmed glaucoma valve implantation in Mexican patients with neovascular glaucoma (NVG). We reviewed records of 60 eyes of 60 patients with NVG who underwent Ahmed valve implantation, with a follow-up period of 1 year. We identified successful and failed cases and compared baseline and follow-up characteristics to identify possible differences between both groups. We classified 36 eyes (60%) as successful and 24 (40%) as failed cases. We found a significant difference in success rate in patients who had a hypertensive phase at any time during the follow-up period (OR = 5.15, CI = 1.49-20.15, p = 0.004). Patients in the success group showed a statistically significant decrease in the number of glaucoma medications 1 year after surgery (p Ahmed valve surgical failure in patients with NVG. How to cite this article: Hernandez-Oteyza A, Lazcano-Gomez G, Jimenez-Roman J, Hernandez-Garciadiego C. Surgical Outcome of Ahmed Valve Implantation in Mexican Patients with Neovascular Glaucoma. J Curr Glaucoma Pract 2014;8(3):86-90.

  7. Therapeutic Effect of Novel Single-Stranded RNAi Agent Targeting Periostin in Eyes with Retinal Neovascularization

    Directory of Open Access Journals (Sweden)

    Takahito Nakama

    2017-03-01

    Full Text Available Retinal neovascularization (NV due to retinal ischemia remains one of the principal causes of vision impairment in patients with ischemic retinal diseases. We recently reported that periostin (POSTN may play a role in the development of preretinal fibrovascular membranes, but its role in retinal NV has not been determined. The purpose of this study was to examine the expression of POSTN in the ischemic retinas of a mouse model of oxygen-induced retinal NV. We also studied the function of POSTN on retinal NV using Postn KO mice and human retinal endothelial cells (HRECs in culture. In addition, we used a novel RNAi agent, NK0144, which targets POSTN to determine its effect on the development of retinal NV. Our results showed that the expression of POSTN was increased in the vascular endothelial cells, pericytes, and M2 macrophages in ischemic retinas. POSTN promoted the ischemia-induced retinal NV by Akt phosphorylation through integrin αvβ3. NK0144 had a greater inhibitory effect than canonical double-stranded siRNA on preretinal pathological NV in vivo and in vitro. These findings suggest a causal relationship between POSTN and retinal NV, and indicate a potential therapeutic role of intravitreal injection of NK0144 for retinal neovascular diseases.

  8. Neocellularization and neovascularization of nanosized bioactive glass-coated decellularized trabecular bone scaffolds

    KAUST Repository

    Gerhardt, Lutz Christian

    2012-09-11

    In this study, the in vivo recellularization and neovascularization of nanosized bioactive glass (n-BG)-coated decellu-larized trabecular bone scaffolds were studied in a rat model and quantified using stereological analyses. Based on the highest amount of vascular endothelial growth factor (VEGF) secreted by human fibroblasts grown on n-BG coatings (0-1.245 mg/cm 2), decellularized trabecular bone samples (porosity: 43-81%) were coated with n-BG particles. Grown on n-BG particles at a coating density of 0.263 mg/cm2, human fibroblasts produced 4.3 times more VEGF than on uncoated controls. After 8 weeks of implantation in Sprague-Dawley rats, both uncoated and n-BG-coated samples were well infiltrated with newly formed tissue (47-48%) and blood vessels (3-4%). No significant differences were found in cellularization and vascularization between uncoated bone scaffolds and n-BG-coated scaffolds. This finding indicates that the decellularized bone itself may exhibit growth-promoting properties induced by the highly interconnected pore microarchitecture and/or proteins left behind on decellularized scaffolds. Even if we did not find proangiogenic effects in n-BG-coated bone scaffolds, a bioactive coating is considered to be beneficial to impart osteoinductive and osteoconductive properties to decellularized bone. n-BG-coated bone grafts have thus high clinical potential for the regeneration of complex tissue defects given their ability for recellularization and neovascularization. © 2012 Wiley Periodicals, Inc.

  9. Gemcitabine-induced CXCL8 expression counteracts its actions by inducing tumor neovascularization

    Energy Technology Data Exchange (ETDEWEB)

    Song, Yao; Baba, Tomohisa [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan); Li, Ying-Yi [Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Furukawa, Kaoru; Tanabe, Yamato [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan); School of Natural System Bioengineering Course, College of Science and Engineering, Kanazawa University, Kanazawa, Ishikawa (Japan); Matsugo, Seiichi [School of Natural System Bioengineering Course, College of Science and Engineering, Kanazawa University, Kanazawa, Ishikawa (Japan); Sasaki, Soichiro [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan); Mukaida, Naofumi, E-mail: mukaida@staff.kanazawa-u.ac.jp [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan)

    2015-03-06

    Patients with pancreatic ductal adenocarcinoma (PDAC) are frequently complicated with metastatic disease or locally advanced tumors, and consequently need chemotherapy. Gemcitabine is commonly used for PDAC treatment, but with limited efficacy. The capacity of gemcitabine to generate reactive oxygen species (ROS) in human pancreatic cancer cells, prompted us to examine its effects on the expression of pro-inflammatory cytokines and chemokines. We observed that gemcitabine enhanced selectively the expression of CXCL8 in human pancreatic cancer cells through ROS generation and NF-κB activation. In vitro blocking of CXCL8 failed to modulate gemcitabine-mediated inhibition of cell proliferation in human pancreatic cancer cells. Gemcitabine also enhanced CXCL8 expression in pancreatic cancer cells in xenografted tumor tissues. Moreover, anti-CXCL8 antibody treatment in vivo attenuated tumor formation as well as intra-tumoral vascularity in nude mice, which were transplanted with Miapaca-2 cells and treated with gemcitabine. Thus, gemcitabine-induced CXCL8 may counteract the drug through inducing neovascularization. - Highlights: • Gemcitabine induced CXCL8 expression in human pancreatic cancer cells. • CXCL8 expression required ROS generation and NF-κB activation. • CXCL8 did not affect in vitro proliferation of human pancreatic cancer cells. • CXCL8 in vivo counteracted gemcitabine by inducing neovascularization.

  10. Inhibitory Effects of Glycyrrhiza glabra and Its Major Constituent Glycyrrhizin on Inflammation-Associated Corneal Neovascularization

    Directory of Open Access Journals (Sweden)

    Syed Luqman Shah

    2018-01-01

    Full Text Available Glycyrrhiza glabra L. (Leguminosae is widely used in folk medicines. Glycyrrhizin, an active compound of G. glabra, possesses anti-inflammatory activity. This study investigates the G. glabra methanol extract and glycyrrhizin for the treatment of corneal neovascularization (CNV. G. glabra was extracted in 70% aqueous methanol. Phytochemical tests, thin layer chromatography (TLC, and high performance liquid chromatography (HPLC were used for the analysis of chemical composition. The topical solution of G. glabra methanol extract (2% w/v and glycyrrhizin (1% w/v was prepared in normal saline. After corneal burn (1 N NaOH, animals were left untreated for a week so that neovascularization appears in all groups. Treatments started on day 7 and continued for next 21 consecutive days. The animals were treated with 3 drops of various topical solutions thrice a day. Digital photograph analysis and histological studies were used for the evaluation of CNV. Phytochemical analysis of the G. glabra methanol extract showed the presence of saponins, phenols, carbohydrates, flavonoids, and proteins. TLC and HPLC confirmed the presence of glycyrrhizin. Photograph analysis of the extract and glycyrrhizin treated group showed a considerable decrease in CNV. Histological study of G. glabra and glycyrrhizin treated groups showed no blood vessels with properly arranged collagen fibers. This study showed that G. glabra and glycyrrhizin can be used for the treatment of CNV. Bioassay guided isolation can lead to preparation of ophthalmic solutions for the treatment of CNV.

  11. Low-dose radiation therapy for choroidal neovascularization in age-related macular degeneration

    International Nuclear Information System (INIS)

    Matsuhashi, Hideaki; Takahashi, Daisuke; Mariya, Yasushi; Tarusawa, Nobuko; Yoshimoto, Hiroshi; Matsuyama, Shuichi; Noda, Yasuko.

    1996-01-01

    The efficacy of low-dose radiation was evaluated in the treatment of eyes with subfoveal or juxtafoveal choroidal neovascularization in age-related macular degeneration. Ten eyes of ten patients received a total dose of 14 Gy of 10 MV X-rays in seven fractions and the mean follow-up time was 12 months (range 9-18 months). Thirteen control eyes of thirteen patients were followed for an average of 18 months (range 12-24 months). Visual acuity was improved in 2 eyes (20%), unchanged in 3 eyes (30%), and deteriorated in 5 eyes (50%) of treated patients, and it was improved in no eyes (0%), unchanged in 5 eyes (32%), and deteriorated in 8 eyes (50%) of the control patients at their last follow-up examinations. Funduscopic and angiographic findings were improved in 3 eyes (30%), unchanged in 2 eyes (20%), and deteriorated in 5 eyes (50%) of treated patients, and they were improved in no eyes (0%), unchanged in 5 eyes (32%), and deteriorated in 8 eyes (50%) of the control patients. These results suggested that low-dose radiation is beneficial for the management of subfoveal or juxtafoveal choroidal neovascularization in age-related macular degeneration. (author)

  12. Radiation therapy for small choroidal neovascularization in age-related macular degeneration

    International Nuclear Information System (INIS)

    Matsuhashi, Hideaki; Noda, Yasuko; Takahashi, Daisuke; Mariya, Yasushi

    2000-01-01

    The purpose of this study was to evaluate the effects of radiation therapy on age-related macular degeneration with subfoveal or juxtafoveal choroidal neovascularization ≤1 disc area. Fourteen patients (14 eyes) received a total radiation dose of 10-20 Gy in 5-10 fractions. The mean follow-up time was 22 months. Ten patients (10 eyes) in a control group were followed up for an average of 16 months without treatment. At a 12-month posttreatment examination, funduscopic and angiographic findings showed improvement in 7 eyes (50%), no change in 1 eye (7%), and deterioration in 6 eyes (43%) among the treated patients. The same findings demonstrated improvement in 1 eye (10%), no change in 2 eyes (20%), and deterioration in 7 eyes (70%) among the control patients. This difference was determined to be statistically significant between the two groups by the Mann-Whitney U-test. Visual acuity had improved in 4 eyes (29%), was unchanged in 6 eyes (43%), and had declined in 4 eyes (29%), among the treated patients. Among the control patients, visual acuity had improved in none of the eyes (0%), was unchanged in 6 eyes (60%), and had declined in 4 eyes (40%). The difference in visual acuity between the two groups was not statistically significant. Radiation therapy inhibited small choroidal neovascularization, as seen by funduscopy and angiography, but its effectiveness in improving visual prognosis was not always evident. (author)

  13. Radiation therapy for small choroidal neovascularization in age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Matsuhashi, Hideaki; Noda, Yasuko; Takahashi, Daisuke; Mariya, Yasushi [Hirosaki Univ., Aomori (Japan). School of Medicine

    2000-12-01

    The purpose of this study was to evaluate the effects of radiation therapy on age-related macular degeneration with subfoveal or juxtafoveal choroidal neovascularization {<=}1 disc area. Fourteen patients (14 eyes) received a total radiation dose of 10-20 Gy in 5-10 fractions. The mean follow-up time was 22 months. Ten patients (10 eyes) in a control group were followed up for an average of 16 months without treatment. At a 12-month posttreatment examination, funduscopic and angiographic findings showed improvement in 7 eyes (50%), no change in 1 eye (7%), and deterioration in 6 eyes (43%) among the treated patients. The same findings demonstrated improvement in 1 eye (10%), no change in 2 eyes (20%), and deterioration in 7 eyes (70%) among the control patients. This difference was determined to be statistically significant between the two groups by the Mann-Whitney U-test. Visual acuity had improved in 4 eyes (29%), was unchanged in 6 eyes (43%), and had declined in 4 eyes (29%), among the treated patients. Among the control patients, visual acuity had improved in none of the eyes (0%), was unchanged in 6 eyes (60%), and had declined in 4 eyes (40%). The difference in visual acuity between the two groups was not statistically significant. Radiation therapy inhibited small choroidal neovascularization, as seen by funduscopy and angiography, but its effectiveness in improving visual prognosis was not always evident. (author)

  14. Low-dose radiation therapy for choroidal neovascularization in age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Matsuhashi, Hideaki; Takahashi, Daisuke; Mariya, Yasushi; Tarusawa, Nobuko; Yoshimoto, Hiroshi; Matsuyama, Shuichi [Hirosaki Univ., Aomori (Japan). School of Medicine; Noda, Yasuko

    1996-10-01

    The efficacy of low-dose radiation was evaluated in the treatment of eyes with subfoveal or juxtafoveal choroidal neovascularization in age-related macular degeneration. Ten eyes of ten patients received a total dose of 14 Gy of 10 MV X-rays in seven fractions and the mean follow-up time was 12 months (range 9-18 months). Thirteen control eyes of thirteen patients were followed for an average of 18 months (range 12-24 months). Visual acuity was improved in 2 eyes (20%), unchanged in 3 eyes (30%), and deteriorated in 5 eyes (50%) of treated patients, and it was improved in no eyes (0%), unchanged in 5 eyes (32%), and deteriorated in 8 eyes (50%) of the control patients at their last follow-up examinations. Funduscopic and angiographic findings were improved in 3 eyes (30%), unchanged in 2 eyes (20%), and deteriorated in 5 eyes (50%) of treated patients, and they were improved in no eyes (0%), unchanged in 5 eyes (32%), and deteriorated in 8 eyes (50%) of the control patients. These results suggested that low-dose radiation is beneficial for the management of subfoveal or juxtafoveal choroidal neovascularization in age-related macular degeneration. (author)

  15. Radiation therapy for small choroidal neovascularization in age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Matsuhashi, Hideaki; Noda, Yasuko; Takahashi, Daisuke; Mariya, Yasushi [Hirosaki Univ., Aomori (Japan). School of Medicine

    1999-06-01

    Radiation therapy for age-related macular degeneration with subfoveal or juxtafoveal choroidal neovascularization smaller than or equal to 1 disc area was evaluated. Fourteen eyes received a total radiation dose of 10-20 Gy in 5-10 fractions. The mean follow-up time was 22 months. Ten eyes in a control group were followed for an average of 16 months without any treatment. At a 12-month follow-up examination, funduscopic and angiographic findings had improved in 7 eyes (50%), were unchanged in 1 eye (7%) and, had deteriorated in 6 eyes (43%) among the treated patients. The same findings had improved in 1 eye (10%), were unchanged in 2 eyes (20%), and had deteriorated in 7 eyes (70%) among the control patients. There was a statistically significant difference by Mann-Whitney U test between the two groups. Visual acuity had improved in 4 eyes (29%), was unchanged in 6 eyes (43%), and had declined in 4 eyes (29%) among the treated patients. Among the control patients visual acuity had improved in none of the eyes (0%), was unchanged in 6 eyes (60%), and had declined in 4 eyes (40%). The difference between the two groups was not statistically significant. Of the 7 cases whose fundus had improved by 12 months, 4 cases maintained a favorable status through the following 2 years. Radiation therapy had an inhibitory effect on small choroidal neovascularization when viewed by funduscopy and angiography, but, the efficacy for visual prognosis was not always identified. (author)

  16. RISK FACTORS AND CLINICAL SIGNIFICANCE OF PRECHOROIDAL CLEFT IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

    Science.gov (United States)

    Kim, Jong Min; Kang, Se Woong; Son, Dae Yong; Bae, Kunho

    2017-11-01

    To investigate the risk factors associated with prechoroidal cleft occurrence after treatment for neovascular age-related macular degeneration (nAMD) and to elucidate its clinical significance. Two hundred thirty-four subjects who were treated for neovascular age-related macular degeneration were assessed to identify prechoroidal cleft on optical coherence tomography. Clinical variables were compared between patients manifesting a cleft (cleft group) and patients who did not (control group). Prechoroidal cleft was detected in 29 of 234 patients (8.1%). Although the baseline visual acuity was not different between the 2 groups, logMAR visual acuity at final visit was 0.89 ± 0.74 (with approximate Snellen equivalent of 20/160) in the cleft group and 0.65 ± 0.69 (with approximate Snellen equivalent of 20/100) in controls (P age-related macular degeneration (P age-related macular degeneration, and a submacular hemorrhage treated by pneumatic displacement were the independent risk factors for development of prechoroidal cleft. Eyes with a cleft, especially clefts that develop early, generally had worse prognoses than eyes without clefts.

  17. JNK inhibition reduces apoptosis and neovascularization in a murine model of age-related macular degeneration.

    Science.gov (United States)

    Du, Hongjun; Sun, Xufang; Guma, Monica; Luo, Jing; Ouyang, Hong; Zhang, Xiaohui; Zeng, Jing; Quach, John; Nguyen, Duy H; Shaw, Peter X; Karin, Michael; Zhang, Kang

    2013-02-05

    Age-related macular degeneration (AMD) is the leading cause of registered blindness among the elderly and affects over 30 million people worldwide. It is well established that oxidative stress, inflammation, and apoptosis play critical roles in pathogenesis of AMD. In advanced wet AMD, although, most of the severe vision loss is due to bleeding and exudation of choroidal neovascularization (CNV), and it is well known that vascular endothelial growth factor (VEGF) plays a pivotal role in the growth of the abnormal blood vessels. VEGF suppression therapy improves visual acuity in AMD patients. However, there are unresolved issues, including safety and cost. Here we show that mice lacking c-Jun N-terminal kinase 1 (JNK1) exhibit decreased inflammation, reduced CNV, lower levels of choroidal VEGF, and impaired choroidal macrophage recruitment in a murine model of wet AMD (laser-induced CNV). Interestingly, we also detected a substantial reduction in choroidal apoptosis of JNK1-deficient mice. Intravitreal injection of a pan-caspase inhibitor reduced neovascularization in the laser-induced CNV model, suggesting that apoptosis plays a role in laser-induced pathological angiogenesis. Intravitreal injection of a specific JNK inhibitor decreased choroidal VEGF expression and reduced pathological CNV. These results suggest that JNK1 plays a key role in linking oxidative stress, inflammation, macrophage recruitment apoptosis, and VEGF production in wet AMD and pharmacological JNK inhibition offers a unique and alternative avenue for prevention and treatment of AMD.

  18. Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells

    International Nuclear Information System (INIS)

    Suetsugu, Atsushi; Nagaki, Masahito; Aoki, Hitomi; Motohashi, Tsutomu; Kunisada, Takahiro; Moriwaki, Hisataka

    2006-01-01

    The CD133 antigen, identified as a hematopoietic stem cell marker, appears in various human embryonic epithelia including the neural tube, gut, and kidney. We herein investigated whether CD133 + cells isolated from human hepatocellular carcinoma cell lines possess cancer stem/progenitor cell-like properties. Among the three cell lines studied, the CD133 antigen was found to be expressed only on the surface of Huh-7 cells. CD133 + cells from Huh-7 performed a higher in vitro proliferative potential and lower mRNA expressions of mature hepatocyte markers, glutamine synthetase and cytochrome P450 3A4, than CD133 - population of Huh-7 cells. When either CD133 + or CD133 - cells were subcutaneously injected into SCID mice, CD133 + cells formed tumors, whereas CD133 - cells induced either a very small number of tumors or none at all. Taken together, the identification of CD133 + cells could thus be a potentially powerful tool to investigate the tumorigenic process in the hepatoma system and to also develop effective therapies targeted against hepatocellular carcinoma

  19. The hematopoietic transcription factor PU.1 regulates RANK gene expression in myeloid progenitors

    International Nuclear Information System (INIS)

    Kwon, Oh Hyung; Lee, Chong-Kil; Lee, Young Ik; Paik, Sang-Gi; Lee, Hyun-Jun

    2005-01-01

    Osteoclasts are bone resorbing cells of hematopoietic origin. The hematopoietic transcription factor PU.1 is critical for osteoclastogenesis; however, the molecular mechanisms of PU.1-regulated osteoclastogenesis have not been explored. Here, we present evidence that the receptor activator of nuclear factor κB (RANK) gene that has been shown to be crucial for osteoclastogenesis is a transcriptional target of PU.1. The PU.1 -/- progenitor cells failed to express the RANK gene and reconstitution of PU.1 in these cells induced RANK expression. Treatment of the PU.1 reconstituted cells with M-CSF and RANKL further augmented the RANK gene expression. To explore the regulatory mechanism of the RANK gene expression by PU.1, we have cloned the human RANK promoter. Transient transfection assays have revealed that the 2.2-kb RANK promoter was functional in a monocyte line RAW264.7, whereas co-transfection of PU.1 transactivated the RANK promoter in HeLa cells. Taken together, these results suggest that PU.1 regulates the RANK gene transcription and this may represent one of the key roles of PU.1 in osteoclast differentiation

  20. Neovascular age-related macular degeneration without drusen in the fellow eye : clinical spectrum and therapeutic outcome

    NARCIS (Netherlands)

    Chung, Wing H; van Dijk, Elon H C; Mohabati, Danial; Dijkman, Greet; Yzer, Suzanne; de Jong, Eiko K; Fauser, Sascha; Schlingemann, Reinier O; Hoyng, Carel B; Boon, Camiel J F

    2017-01-01

    PURPOSE: To investigate the clinical characteristics and therapeutic outcome of patients with neovascular age-related macular degeneration (nAMD) in 1 eye, without drusen in the fellow eye. PATIENTS AND METHODS: Medical records of 381 patients were analyzed to identify the cases. The main outcomes

  1. Neovascular age-related macular degeneration without drusen in the fellow eye: clinical spectrum and therapeutic outcome

    NARCIS (Netherlands)

    Chung, Wing H.; van Dijk, Elon H. C.; Mohabati, Danial; Dijkman, Greet; Yzer, Suzanne; de Jong, Eiko K.; Fauser, Sascha; Schlingemann, Reinier O.; Hoyng, Carel B.; Boon, Camiel J. F.

    2017-01-01

    Purpose: To investigate the clinical characteristics and therapeutic outcome of patients with neovascular age-related macular degeneration (nAMD) in 1 eye, without drusen in the fellow eye. Patients and methods: Medical records of 381 patients were analyzed to identify the cases. The main outcomes

  2. Safety and Efficacy of a Flexible Dosing Regimen of Ranibizumab in Neovascular Age-Related Macular Degeneration: The SUSTAIN Study

    NARCIS (Netherlands)

    Holz, Frank G.; Amoaku, Winfried; Donate, Juan; Guymer, Robyn H.; Kellner, Ulrich; Schlingemann, Reinier O.; Weichselberger, Andreas; Staurenghi, Giovanni

    2011-01-01

    Objective: To evaluate the safety and efficacy of individualized ranibizumab treatment in patients with neovascular age-related macular degeneration. Design: Twelve-month, phase III, multicenter, open-label, single-arm study. Participants: A total of 513 ranibizumab-naive SUSTAIN patients.

  3. Neovascular age-related macular degeneration treated with ranibizumab or aflibercept in the same large clinical setting

    DEFF Research Database (Denmark)

    Rasmussen, Annette; Sander, Birgit; Larsen, Michael

    2017-01-01

    PURPOSE: To study visual outcome and number of annual injections in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) before and after a change in first-line therapy from ranibizumab to aflibercept in a high-volume clinical practice. METHODS: This was a retrospective...

  4. In patients with neovascular age-related macular degeneration, physical activity may influence C-reactive protein levels

    DEFF Research Database (Denmark)

    Subhi, Yousif; Singh, Amardeep; Falk, Mads Krüger

    2014-01-01

    Association of neovascular age-related macular degeneration (AMD) with C-reactive protein (CRP) was previously reported, indicating a relation to systemic low-grade inflammation. However, visual impairment limits physical activity, and physical activity modulates CRP levels. Here, we investigated...

  5. Long-term longitudinal study of patients treated with ranibizumab for neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Rasmussen, Annette; Sander, Birgit

    2014-01-01

    PURPOSE OF REVIEW: To review the current literature regarding long-term treatment beyond 2 years with anti-vascular endothelial growth factor (VEGF) inhibition for neovascular age-related macular degeneration (nv-AMD). RECENT FINDINGS: Only few studies of anti-VEGF treatment for nv-AMD exist beyond...

  6. PET imaging of adoptive progenitor cell therapies

    International Nuclear Information System (INIS)

    Gelovani, Juri G.

    2008-01-01

    The overall objective of this application is to develop novel technologies for non-invasive imaging of adoptive stem cell-based therapies with positron emission tomography (PET) that would be applicable to human patients. To achieve this objective, stem cells will be genetically labeled with a PET-reporter gene and repetitively imaged to assess their distribution, migration, differentiation, and persistence using a radiolabeled reporter probe. This new imaging technology will be tested in adoptive progenitor cell-based therapy models in animals, including: delivery pro-apoptotic genes to tumors, and T-cell reconstitution for immunostimulatory therapy during allogeneic bone marrow progenitor cell transplantation. Technical and Scientific Merits. Non-invasive whole body imaging would significantly aid in the development and clinical implementation of various adoptive progenitor cell-based therapies by providing the means for non-invasive monitoring of the fate of injected progenitor cells over a long period of observation. The proposed imaging approaches could help to address several questions related to stem cell migration and homing, their long-term viability, and their subsequent differentiation. The ability to image these processes non-invasively in 3D and repetitively over a long period of time is very important and will help the development and clinical application of various strategies to control and direct stem cell migration and differentiation. Approach to accomplish the work. Stem cells will be genetically with a reporter gene which will allow for repetitive non-invasive 'tracking' of the migration and localization of genetically labeled stem cells and their progeny. This is a radically new approach that is being developed for future human applications and should allow for a long term (many years) repetitive imaging of the fate of tissues that develop from the transplanted stem cells. Why the approach is appropriate. The novel approach to stem cell imaging

  7. Cardiac Progenitor Cell Extraction from Human Auricles

    KAUST Repository

    Di Nardo, Paolo

    2017-02-22

    For many years, myocardial tissue has been considered terminally differentiated and, thus, incapable of regenerating. Recent studies have shown, instead, that cardiomyocytes, at least in part, are slowly substituted by new cells originating by precursor cells mostly embedded into the heart apex and in the atria. We have shown that an elective region of progenitor cell embedding is represented by the auricles, non-contractile atria appendages that can be easily sampled without harming the patient. The protocol here reported describes how from auricles a population of multipotent, cardiogenic cells can be isolated, cultured, and differentiated. Further studies are needed to fully exploit this cell population, but, sampling auricles, it could be possible to treat cardiac patients using their own cells circumventing rejection or organ shortage limitations.

  8. PET imaging of adoptive progenitor cell therapies.

    Energy Technology Data Exchange (ETDEWEB)

    Gelovani, Juri G.

    2008-05-13

    Objectives. The overall objective of this application is to develop novel technologies for non-invasive imaging of adoptive stem cell-based therapies with positron emission tomography (PET) that would be applicable to human patients. To achieve this objective, stem cells will be genetically labeled with a PET-reporter gene and repetitively imaged to assess their distribution, migration, differentiation, and persistence using a radiolabeled reporter probe. This new imaging technology will be tested in adoptive progenitor cell-based therapy models in animals, including: delivery pro-apoptotic genes to tumors, and T-cell reconstitution for immunostimulatory therapy during allogeneic bone marrow progenitor cell transplantation. Technical and Scientific Merits. Non-invasive whole body imaging would significantly aid in the development and clinical implementation of various adoptive progenitor cell-based therapies by providing the means for non-invasive monitoring of the fate of injected progenitor cells over a long period of observation. The proposed imaging approaches could help to address several questions related to stem cell migration and homing, their long-term viability, and their subsequent differentiation. The ability to image these processes non-invasively in 3D and repetitively over a long period of time is very important and will help the development and clinical application of various strategies to control and direct stem cell migration and differentiation. Approach to accomplish the work. Stem cells will be genetically with a reporter gene which will allow for repetitive non-invasive “tracking” of the migration and localization of genetically labeled stem cells and their progeny. This is a radically new approach that is being developed for future human applications and should allow for a long term (many years) repetitive imaging of the fate of tissues that develop from the transplanted stem cells. Why the approach is appropriate. The novel approach to

  9. A Proinflammatory Function of Toll-Like Receptor 2 in the Retinal Pigment Epithelium as a Novel Target for Reducing Choroidal Neovascularization in Age-Related Macular Degeneration.

    Science.gov (United States)

    Feng, Lili; Ju, Meihua; Lee, Kei Ying V; Mackey, Ashley; Evangelista, Mariasilvia; Iwata, Daiju; Adamson, Peter; Lashkari, Kameran; Foxton, Richard; Shima, David; Ng, Yin Shan

    2017-10-01

    Current treatments for choroidal neovascularization, a major cause of blindness for patients with age-related macular degeneration, treat symptoms but not the underlying causes of the disease. Inflammation has been strongly implicated in the pathogenesis of choroidal neovascularization. We examined the inflammatory role of Toll-like receptor 2 (TLR2) in age-related macular degeneration. TLR2 was robustly expressed by the retinal pigment epithelium in mouse and human eyes, both normal and with macular degeneration/choroidal neovascularization. Nuclear localization of NF-κB, a major downstream target of TLR2 signaling, was detected in the retinal pigment epithelium of human eyes, particularly in eyes with advanced stages of age-related macular degeneration. TLR2 antagonism effectively suppressed initiation and growth of spontaneous choroidal neovascularization in a mouse model, and the combination of anti-TLR2 and antivascular endothelial growth factor receptor 2 yielded an additive therapeutic effect on both area and number of spontaneous choroidal neovascularization lesions. Finally, in primary human fetal retinal pigment epithelium cells, ligand binding to TLR2 induced robust expression of proinflammatory cytokines, and end products of lipid oxidation had a synergistic effect on TLR2 activation. Our data illustrate a functional role for TLR2 in the pathogenesis of choroidal neovascularization, likely by promoting inflammation of the retinal pigment epithelium, and validate TLR2 as a novel therapeutic target for reducing choroidal neovascularization. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  10. Cytokinetics and Regulation of Progenitor Cells

    Energy Technology Data Exchange (ETDEWEB)

    Lajtha, L. G. [Paterson Laboratories, Christie Hospital and Holt Radium Institute, Manchester (United Kingdom)

    1967-07-15

    Full text: In spite of great differences in the life-span of fully differentiated haemic cells, the cellular kinetics of their production appears to be similar. Recent evidence indicates a common ultimate stem cell for most of the cells in the peripheral blood. The various pathways of differentiation, however, result in transient dividing and differentiating cell populations which differ from each other not only in their specific biochemical processes but also in the manner of control and kinetic pattern of their proliferation. The population best understood is the erythroid progenitor series of cells, primarily because it has the greatest number of experimentally measurable parameters at the present. This will be discussed in detail and comparisons will be made with the myeloid and lymphoid progenitor populations. The fine structure of the bone-marrow stem cell population will be examined in particular, with regard to the suitability or otherwise of the current stem cell models to explain the kinetic pattern of all the peripheral blood elements after perturbations of their steady-state values. Four different assay methods of bone-marrow stem cells have been examined with regard to the kinetic pattern following perturbation of the steady-state system, e.g. by irradiation. Basically, the stem cell assays fall into two categories: those depending on grafting haemopoietic cells into suitably treated recipients, and those in which recovery of the population is allowed in the animal in which the perturbation was produced, without handling the cells. Evidence is accumulating which indicates that in the grafting techniques, a selective loss of stem cells may occur, . especially stem cells in cell cycle, hence in early stages of recovery of the population unduly low numerical values might be noted. In view of this observation, the concept of the colony-forming cell may have to be revised and instead the colony-forming property of the stem cell introduced. (author)

  11. A COMPREHENSIVE PROGENITOR MODEL FOR SNe Ia

    International Nuclear Information System (INIS)

    Meng, X.; Yang, W.

    2010-01-01

    Although the nature of the progenitor of Type Ia supernovae (SNe Ia) is still unclear, the single-degenerate (SD) channel for the progenitor is currently accepted, in which a carbon-oxygen white dwarf (CO WD) accretes hydrogen-rich material from its companion, increases its mass to the Chandrasekhar mass limit, and then explodes as an SN Ia. The companion may be a main sequence or a slightly evolved star (WD + MS), or a red giant star (WD + RG). Incorporating the effect of mass stripping and accretion-disk instability on the evolution of the WD binary, we carried out binary stellar evolution calculations for more than 1600 close WD binaries. As a result, the initial parameter spaces for SNe Ia are presented in an orbital period-secondary mass (log P i , M i 2 ) plane. We confirmed that in a WD + MS system, the initial companion leading to SNe Ia may have mass from 1 M sun to 5 M sun . The initial WD mass for SNe Ia from WD + MS channel is as low as 0.565 M sun , while the lowest WD mass from the WD + RG channel is 1.0 M sun . Adopting the above results, we studied the birth rate of SNe Ia via a binary population synthesis approach. We found that the Galactic SNe Ia birth rate from SD model is (2.55-2.9) x 10 -3 yr -1 (including WD + He star channel), which is slightly smaller than that from observation. If a single starburst is assumed, the distribution of the delay time of SNe Ia from the SD model may be a weak bimodality, where WD + He channel contributes to SNe Ia with delay time shorter than 10 8 yr and WD + RG channel to those with age longer than 6 Gyr.

  12. Cytokinetics and Regulation of Progenitor Cells

    International Nuclear Information System (INIS)

    Lajtha, L.G.

    1967-01-01

    Full text: In spite of great differences in the life-span of fully differentiated haemic cells, the cellular kinetics of their production appears to be similar. Recent evidence indicates a common ultimate stem cell for most of the cells in the peripheral blood. The various pathways of differentiation, however, result in transient dividing and differentiating cell populations which differ from each other not only in their specific biochemical processes but also in the manner of control and kinetic pattern of their proliferation. The population best understood is the erythroid progenitor series of cells, primarily because it has the greatest number of experimentally measurable parameters at the present. This will be discussed in detail and comparisons will be made with the myeloid and lymphoid progenitor populations. The fine structure of the bone-marrow stem cell population will be examined in particular, with regard to the suitability or otherwise of the current stem cell models to explain the kinetic pattern of all the peripheral blood elements after perturbations of their steady-state values. Four different assay methods of bone-marrow stem cells have been examined with regard to the kinetic pattern following perturbation of the steady-state system, e.g. by irradiation. Basically, the stem cell assays fall into two categories: those depending on grafting haemopoietic cells into suitably treated recipients, and those in which recovery of the population is allowed in the animal in which the perturbation was produced, without handling the cells. Evidence is accumulating which indicates that in the grafting techniques, a selective loss of stem cells may occur, . especially stem cells in cell cycle, hence in early stages of recovery of the population unduly low numerical values might be noted. In view of this observation, the concept of the colony-forming cell may have to be revised and instead the colony-forming property of the stem cell introduced. (author)

  13. THE PROGENITOR OF THE TYPE IIb SN 2008ax REVISITED

    Energy Technology Data Exchange (ETDEWEB)

    Folatelli, Gastón; Bersten, Melina C.; Benvenuto, Omar G. [Instituto de Astrofísica de La Plata (Argentina); Kuncarayakti, Hanindyo [Millennium Institute of Astrophysics (MAS), Casilla 36-D, Santiago (Chile); Maeda, Keiichi; Nomoto, Ken’ichi, E-mail: gaston@fcaglp.unlp.edu.ar [Kavli Institute for the Physics and Mathematics of the Universe (WPI), The University of Tokyo, Kashiwa, Chiba 277-8583 (Japan)

    2015-10-01

    Hubble Space Telescope observations of the site of the supernova (SN) SN 2008ax obtained in 2011 and 2013 reveal that the possible progenitor object detected in pre-explosion images was in fact multiple. Four point sources are resolved in the new, higher-resolution images. We identify one of the sources with the fading SN. The other three objects are consistent with single supergiant stars. We conclude that their light contaminated the previously identified progenitor candidate. After subtraction of these stars, the progenitor appears to be significantly fainter and bluer than previously measured. Post-explosion photometry at the SN location indicates that the progenitor object has disappeared. If single, the progenitor is compatible with a supergiant star of B to mid-A spectral type, while a Wolf–Rayet (W-R) star would be too luminous in the ultraviolet to account for the observations. Moreover, our hydrodynamical modeling shows that the pre-explosion mass was 4–5 M{sub ⊙} and the radius was 30–50 R{sub ⊙}, which is incompatible with a W-R progenitor. We present a possible interacting binary progenitor computed with our evolutionary models that reproduces all the observational evidence. A companion star as luminous as an O9–B0 main-sequence star may have remained after the explosion.

  14. Ionizing radiation induces apoptosis in hematopoietic stem and progenitor cells

    International Nuclear Information System (INIS)

    Meng, A.; Zhou, D.; Geiger, H.; Zant, G.V.

    2003-01-01

    The aims of this study was to determine if ionizing radiation (IR) induces apoptosis in hematopoietic stem (HSC) and progenitor cells. Lin-cells were isolated from mouse bone marrow (BM) and pretreated with vehicle or 100 μM z-VAD 1 h prior to exposure to 4 Gy IR. The apoptotic and/or necrotic responses of these cells to IR were analyzed by measuring the annexin V and/or 7-AAD staining in HSC and progenitor populations using flow cytometry, and hematopoietic function of these cells was determined by CAFC assay. Exposure of Lin-cells to IR selectively decreased the numbers of HSC and progenitors in association with an increase in apoptosis in a time-dependent manner. Pretreatment of Lin- cells with z-VAD significantly inhibited IR-induced apoptosis and the decrease in the numbers of HSC and progenitors. However, IR alone or in combination with z-VAD did not lead to a significant increase in necrotic cell death in either HSC or progenitors. In addition, pretreatment of BM cells with z-VAD significantly attenuated IR-induced reduction in the frequencies of day-7, -28 and -35 CAFC. Exposure of HSC and progenitors to IR induces apoptosis. The induction of HSC and progenitor apoptosis contributes to IR-induced suppression of their hematopoietic function

  15. THE PROGENITOR OF THE TYPE IIb SN 2008ax REVISITED

    International Nuclear Information System (INIS)

    Folatelli, Gastón; Bersten, Melina C.; Benvenuto, Omar G.; Kuncarayakti, Hanindyo; Maeda, Keiichi; Nomoto, Ken’ichi

    2015-01-01

    Hubble Space Telescope observations of the site of the supernova (SN) SN 2008ax obtained in 2011 and 2013 reveal that the possible progenitor object detected in pre-explosion images was in fact multiple. Four point sources are resolved in the new, higher-resolution images. We identify one of the sources with the fading SN. The other three objects are consistent with single supergiant stars. We conclude that their light contaminated the previously identified progenitor candidate. After subtraction of these stars, the progenitor appears to be significantly fainter and bluer than previously measured. Post-explosion photometry at the SN location indicates that the progenitor object has disappeared. If single, the progenitor is compatible with a supergiant star of B to mid-A spectral type, while a Wolf–Rayet (W-R) star would be too luminous in the ultraviolet to account for the observations. Moreover, our hydrodynamical modeling shows that the pre-explosion mass was 4–5 M ⊙ and the radius was 30–50 R ⊙ , which is incompatible with a W-R progenitor. We present a possible interacting binary progenitor computed with our evolutionary models that reproduces all the observational evidence. A companion star as luminous as an O9–B0 main-sequence star may have remained after the explosion

  16. Ocular neovascularization in eyes with a central retinal artery occlusion or a branch retinal artery occlusion

    Directory of Open Access Journals (Sweden)

    Mason lll JO

    2015-06-01

    Full Text Available John O Mason III,1,2 Shyam A Patel,1 Richard M Feist,1,2 Michael A Albert Jr,1,2 Carrie Huisingh,1 Gerald McGwin Jr,1,3 Martin L Thomley1,2 1Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, AL, USA; 2Retina Consultants of Alabama, Callahan Eye Foundation Hospital, Birmingham, AL, USA; 3Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA Purpose: To investigate the ocular neovascularization (ONV rate in eyes with a branch retinal artery occlusion (BRAO or a central retinal artery occlusion (CRAO, and to study factors that may influence the ONV rate secondary to CRAO.Methods: This was a retrospective case series of consecutive patients (286 total eyes: 83 CRAOs and 203 BRAOs who were diagnosed with a retinal artery occlusion from 1998 to 2013 at the Retina Consultants of Alabama and University of Alabama at Birmingham, Birmingham, AL, USA. Generalized estimating equations were used to evaluate the association between hypothesized risk factors and ONV development.Results: Twelve (14.5% of the 83 eyes with a CRAO developed ONV. Eleven of 12 eyes (91.7% had iris neovascularization, ten of 12 eyes (83.3% had neovascular glaucoma, and two of 12 eyes (16.7% had neovascularization of the optic disc. The average time for ONV development secondary to CRAO was 30.7 days, ranging from the date of presentation to 137 days. Only two (<1.0% of the 203 eyes with a BRAO developed iris neovascularization. Diabetes mellitus type 2 was a risk factor for ONV development following a CRAO with an adjusted odds ratio of 5.2 (95% confidence interval: 1.4–19.8 (P=0.02.Conclusion: ONV is an important complication of CRAO and is a less-frequent complication of BRAO. Patients with a CRAO, especially those with diabetes mellitus type 2, should be closely monitored for the first 6 months for ONV. Keywords: neovascularization, neovascular glaucoma, retinal artery occlusion, central

  17. Radiation effects on regeneration and T-cell-inducing function of the thymus

    International Nuclear Information System (INIS)

    Hirokawa, K.; Sado, T.

    1984-01-01

    Radiation effects on regeneration and T-cell-inducing function of the thymus were studied in three sets of experiments. When TXB mice were grafted with 1-week-old thymus which had been previously irradiated at various doses, an exponential decrease was observed in the morphological regeneration of the thymus grafts and in their T-cell-inducing function at doses of 600 R and over, showing about 10% that of the control at 1500 R. When in situ thymus of adult mice was locally irradiated, the radiation effect on T-cell-inducing function was less pronounced as compared with the first experiment; i.e., about 40% of the control at 1797 R. When in situ thymus of 1-day-old newborn mice was locally irradiated, regeneration potential of 1-day-old newborn thymus was highly resistant to radiation exposure and no effect on immunological functions was observed even by local irradiation of 2000 R

  18. Manipulating Endothelial Progenitor Cell Homing with Sphingosine-1-Phosphate for Terapeutic Angiogenesis

    Science.gov (United States)

    Williams, Priscilla Anne

    Ischemic vascular diseases are the main cause of mortality worldwide and yet current therapies only delay disease progression and improve quality of life without addressing the fundamental problem of tissue loss. Within the field of tissue engineering, therapeutic angiogenesis provides a promising approach to alternatively provide new blood vessel formation via spatiotemporally controlled delivery of proangiogenic agents. Sphingosine-1-phosphate (S1P), a bioactive lysophospholipid that is upregulated under ischemic conditions, has recently gained great enthusiasm as a potential mediator in neovascularization strategies given its essential roles in promoting both neovessel formation and stabilization, and cellular trafficking along highly regulated endogenous gradients. Herein, the governing hypothesis guiding this dissertation is that local biomaterial-controlled delivery of S1P may be used to enhance migration and recruitment of vascular progenitor cells for enhanced therapeutic angiogenesis within ischemic tissue. The initial work in this dissertation investigated the effect of hypoxia on the angiogenic response of both mature and progenitor endothelial cells to S1P stimulation in vitro. Outgrowth endothelial cells (OECs) were isolated from human umbilical cord blood to provide a clinically relevant source of vascular progenitor cells for the studies conducted within this dissertation. S1P stimulation promoted angiogenic activity of both ECs and OECs under both ambient and hypoxic (1%) oxygen tensions. Furthermore, dual therapy with the combination of S1P and vascular endothelial growth factor (VEGF) further enhanced cellular responses. Interestingly, hypoxia substantially augmented the functional response of OECs to S1P, resulting in 25-fold and 6.5-fold increases in directed migration and sprouting, respectively. Thus, these studies highlighted the potential for S1P as a therapeutic agent for treatment of ischemic diseases. An injectable biomaterial system

  19. An assessment of the vulnerability of carotid plaques: a comparative study between intraplaque neovascularization and plaque echogenicity

    International Nuclear Information System (INIS)

    Zhou, Yangyang; Li, Yan; Bai, Yang; Chen, Ying; Sun, Xiaofeng; Zhu, Yingqiao; Wu, Jiang

    2013-01-01

    Carotid plaque echolucency as detected by Color Doppler ultrasonography (CDUS) has been used as a potential marker of plaque vulnerability. However, contrast-enhanced ultrasound (CEUS) has recently been shown to be a valuable method to evaluate the vulnerability and neovascularization within carotid atherosclerotic plaques. The aim of this study was to compare CEUS and CDUS in the assessment of plaque vulnerability using transcranial color Doppler (TCD) monitoring of microembolic signals (MES) as a reference technique. A total of 46 subjects with arterial stenosis (≥ 50%) underwent a carotid duplex ultrasound, TCD monitoring of MES and CEUS (SonoVue doses of 2.0 mL) within a span of 3 days. The agreement between the CEUS, CDUS, and MES findings was assessed with a chi-square test. A p-value less than 0.05 was considered statistically significant. Neovascularization was observed in 30 lesions (44.4%). The vascular risk factors for stroke were similar and there were no age or gender differences between the 2 groups. Using CEUS, MES were identified in 2 patients (12.5%) within class 1 (non-neovascularization) as opposed to 15 patients (50.0%) within class 2 (neovascularization) (p = 0.023). CDUS revealed no significant differences in the appearance of the MES between the 2 groups (hyperechoic and hypoechoic) (p = 0.237). This study provides preliminary evidence to suggest that intraplaque neovascularization detected by CEUS is associated with the presence of MESs, where as plaque echogenicity on traditional CDUS does not. These findings argue that CEUS may better identify high-risk plaques

  20. Estimated cases of blindness and visual impairment from neovascular age-related macular degeneration avoided in Australia by ranibizumab treatment.

    Science.gov (United States)

    Mitchell, Paul; Bressler, Neil; Doan, Quan V; Dolan, Chantal; Ferreira, Alberto; Osborne, Aaron; Rochtchina, Elena; Danese, Mark; Colman, Shoshana; Wong, Tien Y

    2014-01-01

    Intravitreal injections of anti-vascular endothelial growth factor agents, such as ranibizumab, have significantly improved the management of neovascular age-related macular degeneration. This study used patient-level simulation modelling to estimate the number of individuals in Australia who would have been likely to avoid legal blindness or visual impairment due to neovascular age-related macular degeneration over a 2-year period as a result of intravitreal ranibizumab injections. The modelling approach used existing data for the incidence of neovascular age-related macular degeneration in Australia and outcomes from ranibizumab trials. Blindness and visual impairment were defined as visual acuity in the better-seeing eye of worse than 6/60 or 6/12, respectively. In 2010, 14,634 individuals in Australia were estimated to develop neovascular age-related macular degeneration who would be eligible for ranibizumab therapy. Without treatment, 2246 individuals would become legally blind over 2 years. Monthly 0.5 mg intravitreal ranibizumab would reduce incident blindness by 72% (95% simulation interval, 70-74%). Ranibizumab given as needed would reduce incident blindness by 68% (64-71%). Without treatment, 4846 individuals would become visually impaired over 2 years; this proportion would be reduced by 37% (34-39%) with monthly intravitreal ranibizumab, and by 28% (23-33%) with ranibizumab given as needed. These data suggest that intravitreal injections of ranibizumab, given either monthly or as needed, can substantially lower the number of cases of blindness and visual impairment over 2 years after the diagnosis of neovascular age-related macular degeneration.

  1. Efficacy of patterned scan laser in treatment of macular edema and retinal neovascularization

    Directory of Open Access Journals (Sweden)

    Dimple Modi

    2009-08-01

    Full Text Available Dimple Modi, Paulpoj Chiranand, Levent AkdumanSaint Louis University School of Medicine, Department of Ophthalmology, Saint Louis University Eye Institute, St. Louis, Missouri, USAPurpose: To analyze the benefits, efficacy, and complications of the PASCAL® photocoagulation laser system (OptiMedica, Santa Clara, CA, USA in patients treated at our institution.Methods: We conducted a retrospective chart review of 19 patients (28 eyes who underwent laser treatment using the PASCAL® photocoagulation system from November 2006 to November 2007. These 28 eyes were divided into two groups; group 1 eyes underwent macular grid laser and group 2 eyes underwent panretinal photocoagulation. Treatment was performed for macular edema or for iris or retinal neovascularization. Outcomes measured included best-corrected visual acuity (BCVA, efficacy of laser treatment, complications, duration of the procedure, and pain perception, which were noted in the charts for panretinal treatments.Results: Follow-up was 5.9 ± 2.6 months for group 1 and 5.9 ± 4.0 months for group 2. In group 1, 9/28 eyes required a second treatment for remaining edema. BCVA was stable or better in 66% (14/21 and average central foveal thickness on ocular coherence tomography improved in 71% (15/21. Time to completion for a number of laser patterns for grid photocoagulation was felt to be too long for completing the total pattern safely, although we have not noted any related complications. In group 2, the neovascularization regressed at least partially in 3/7 patients. Patient-reported pain perception was 3.6 on a scale of 1 to 10 for group 2. Occasional hemorrhages occurred secondary to irregular laser uptake at different spots in the patterns. We observed no visual outcome consequences because of these hemorrhages during follow-up.Conclusions: Retinal photocoagulation by the PASCAL® laser has comparable efficacy to historical results with conventional retinal photocoagulation in short

  2. A circulating microrna profile is associated with late-stage neovascular age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Felix Grassmann

    Full Text Available Age-related macular degeneration (AMD is the leading cause of severe vision impairment in Western populations over 55 years. A growing number of gene variants have been identified which are strongly associated with an altered risk to develop AMD. Nevertheless, gene-based biomarkers which could be dysregulated at defined stages of AMD may point toward key processes in disease mechanism and thus may support efforts to design novel treatment regimens for this blinding disorder. Circulating microRNAs (cmiRNAs which are carried by nanosized exosomes or microvesicles in blood plasma or serum, have been recognized as valuable indicators for various age-related diseases. We therefore aimed to elucidate the role of cmiRNAs in AMD by genome-wide miRNA expression profiling and replication analyses in 147 controls and 129 neovascular AMD patients. We identified three microRNAs differentially secreted in neovascular (NV AMD (hsa-mir-301-3p, pcorrected = 5.6*10-5, hsa-mir-361-5p, pcorrected = 8.0*10-4 and hsa-mir-424-5p, pcorrected = 9.6*10-3. A combined profile of the three miRNAs revealed an area under the curve (AUC value of 0.727 and was highly associated with NV AMD (p = 1.2*10-8. To evaluate subtype-specificity, an additional 59 AMD cases with pure unilateral or bilateral geographic atrophy (GA were analyzed for microRNAs hsa-mir-301-3p, hsa-mir-361-5p, and hsa-mir-424-5p. While we found no significant differences between GA AMD and controls neither individually nor for a combined microRNAs profile, hsa-mir-424-5p levels remained significantly higher in GA AMD when compared to NV (pcorrected<0.005. Pathway enrichment analysis on genes predicted to be regulated by microRNAs hsa-mir-301-3p, hsa-mir-361-5p, and hsa-mir-424-5p, suggests canonical TGFβ, mTOR and related pathways to be involved in NV AMD. In addition, knockdown of hsa-mir-361-5p resulted in increased neovascularization in an in vitro angiogenesis assay.

  3. Regression of peripapillary choroidal neovascular membrane in a patient with sarcoidosis after oral steroid therapy☆

    Science.gov (United States)

    Shoughy, Samir S.; Jaroudi, Mahmoud O.; Tabbara, Khalid F.

    2014-01-01

    Choroidal neovascular membrane (CNV) may occur in patients with posterior uveitis. Treatment of patients with corticosteroids induces regression of the inflammation in the posterior pole with downregulation of many cytokines including vascular endothelial growth factors. We report herewith, a case of biopsy proven sarcoidosis that developed posterior uveitis and peripapillary CNV membrane and subretinal hemorrhage with fluid. The patient was treated with systemic steroids. She demonstrated progressive regression of the CNV membrane and complete resolution of the subretinal hemorrhage and fluids. In conclusion, control of the posterior segment inflammation is crucial in the resolution of the CNV membrane in uveitis and the intravitreal anti-vascular endothelial growth factor may not be always indicated. PMID:24843312

  4. Regression of peripapillary choroidal neovascular membrane in a patient with sarcoidosis after oral steroid therapy.

    Science.gov (United States)

    Shoughy, Samir S; Jaroudi, Mahmoud O; Tabbara, Khalid F

    2014-04-01

    Choroidal neovascular membrane (CNV) may occur in patients with posterior uveitis. Treatment of patients with corticosteroids induces regression of the inflammation in the posterior pole with downregulation of many cytokines including vascular endothelial growth factors. We report herewith, a case of biopsy proven sarcoidosis that developed posterior uveitis and peripapillary CNV membrane and subretinal hemorrhage with fluid. The patient was treated with systemic steroids. She demonstrated progressive regression of the CNV membrane and complete resolution of the subretinal hemorrhage and fluids. In conclusion, control of the posterior segment inflammation is crucial in the resolution of the CNV membrane in uveitis and the intravitreal anti-vascular endothelial growth factor may not be always indicated.

  5. Viability of a jejunal segment after neovascularization by omentoenteropexy Viabilidade de segmento jejunal neovascularizado por omentoenteropexia

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    Mércia Maria Braga Rocha

    2002-01-01

    Full Text Available Omentoenteropexy was developed as an alternative technique to promote neovascularization in an isolated bowel segment. OBJECTIVE: The aim of the present protocol was to study the long-term viability of an isolated jejunal segment following neovascularization by omentoenteropexy. Long-term survival of a neovascularized bowel segment is an indication that the utilization of this segment as an intestinal graft can be successful. METHODS: To test the proposed surgical technique, 13 Wistar rats were subjected to laparotomy, the jejunum was exposed at 20 cm from the angle of Treitz and a pedicle of greater omentum was isolated. An incision of 6 cm was made along the antimesenteric jejunal border, exposing the submucosa. Omentoenteropexy was performed between the incision of the jejunum and the pedicle of the greater omentum. After seven weeks, the mesentery of the jejunal segment subjected to omentoenteropexy was ligated and isolated from the rest of the jejunum by a complete proximal and distal transversal section. Subsequently, an end-to-end anastomosis was performed to restore the continuity of the bowel. RESULTS: At 10 weeks from the first surgical intervention, the isolated jejunal segment subjected to omentoenteropexy was completely neovascularized and viable. CONCLUSION: No evidence of anatomical or functional intestinal obstruction was observed.A omentoenteropexia foi desenvolvida como uma alternativa para técnica de neovascularização em segmentos intestinais isolados, evidenciando algumas vantagens em relação a utilização de órgãos previamente descritos. OBJETIVO: Avaliar a viabilidade de um segmento jejunal neovascularizado por omentoenteropexia. MÉTODOS: Treze ratos Wistar foram submetidos a laparotomia, com exposição do jejuno vinte centímetros após o ligamento de Treitz e obtenção de um pedículo de omento. Na borda antimesentérica do jejuno foi feita uma incisão de seis centímetros com exposição da submucosa intacta

  6. Heparanase-1 activities in the development of laser induced choroidal neovascularization

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    Bao-Ke Hou

    2013-04-01

    Full Text Available AIM:To investigate the role of heparanase-1 in laser-induced choroidal neovascularization (CNV.METHODS:Experimental CNV was induced by krypton laser photocoagulation in 15 male Brown Norway rats. Fundus fluorescein angiography and histopathological examination were performed in observing the CNV development. The expression and distribution of heparanase-1 protein in the laser lesions were determined by immunohistochemistry and western blotting analysis.RESULTS:The success rate of laser induced CNV was approximately 75% on 3-4 weeks after laser photocoagulation. The protein levels of heparanase-1 increased significantly in the retina-choroidal complex of CNV models when compared to normal rat eyes (P<0.01. Immunostaining confirmed strong heparanase-1 expressions in all laser lesions, and it displayed to be highest at the newly formed blood vessels within the fibrovascular complex in the subretinal space.CONCLUSION:Heparanase-1 is closely involved in the development of laser induced CNV.

  7. [Choroidal neovascularization followed in a patient with "Multiple Evanescent White Dot Syndrome" (MEWDS) -- a case report].

    Science.gov (United States)

    Löw, U; Palmowski, A M; Weich, C-M; Ruprecht, K W

    2004-12-01

    Since the description of the "multiple evanescent white dot syndrome" (MEWDS) by Jampol et al, choroiditis has been in the focus of interest. But the classical type of MEWDS was an exceptional case in clinical routine. A 48-year-old female presented to our hospital with a sudden unilateral visual acuity decrease and an extension of the blind spot. Ophthalmoscopy and fluorescein angiography revealed typical multiple grey-white chorioretinal patches of the same stage with lesion areas of about 100 - 200 microm compatible with the diagnose of MEWDS. Although visual acuity increased continuously the patient developed a classical choroidal neovascularization within 4 weeks. She was treated with PDT and visual acuity as well as the ophthalmoscopic diagnosis remained stable. In spite of visual improvement in MEWDS, regular control is recommended. In addition we propose to consider the diagnosis of MEWDS if an enlargement of the blind spot and CNV without lesions of the retinal pigment epithelium are diagnosed.

  8. Evolution of Choroidal Neovascular Membrane in Best Disease after Single Intravitreal Bevacizumab. Case Report.

    Science.gov (United States)

    Celea, Christiana; Pop, Mihai; Avidis-Zamfiroiu, Nicoleta; Celea, Cristian

    2015-03-01

    Best's disease is a hereditary form of macular dystrophy that starts in childhood and progresses until visual symptoms occur. In evolution it can be complicated with choroidal neovascularization, condition very rare in children. We report an important visual improvement in a 8-year-old caucasian girl after successful treatment with one intravitreal bevacizumab injection. There are few cases reported in literature (1-7), and the patient presented here have important particularities: one of the youngest children ever-mentioned with this complication, the third-member of her family with this disease and the first patient who didn't receive a second intravitreal bevacizumab at six weeks after first treatment, even though BCVA was lower than expected. The girl accused decrease of vision in the RE for the past 3-4 months. BCVA at presentation was 1/10. After 6 weeks from the intravitreal treatment, BCVA improved, but not very satisfactory (5/10). Because fundus and OCT aspects were encouraging, we waited another 4 weeks before the second injection. BCVA doubled in this period (8/10). Visual acuity, fundus and OCT aspects stabilized for 18 months of follow-up. We note that choroidal neovascular membrane associated with Best's disease can appear at such young children, this fact being very important in the phase of diagnosis, when the clinician should also take in consideration this possibility. Another important idea underlined here is the long-term efficacy of a single intravitreal anti-VEGF injection and also the no-need for imminent, fast re-treatment when the fundus and OCT aspects are encouraging through the follow-up.

  9. Phthalimide neovascular factor 1 (PNF1) modulates MT1-MMP activity in human microvascular endothelial cells.

    Science.gov (United States)

    Wieghaus, Kristen A; Gianchandani, Erwin P; Neal, Rebekah A; Paige, Mikell A; Brown, Milton L; Papin, Jason A; Botchwey, Edward A

    2009-07-01

    We are creating synthetic pharmaceuticals with angiogenic activity and potential to promote vascular invasion. We previously demonstrated that one of these molecules, phthalimide neovascular factor 1 (PNF1), significantly expands microvascular networks in vivo following sustained release from poly(lactic-co-glycolic acid) (PLAGA) films. In addition, to probe PNF1 mode of action, we recently applied a novel pathway-based compendium analysis to a multi-timepoint, controlled microarray data set of PNF1-treated (vs. control) human microvascular endothelial cells (HMVECs), and we identified induction of tumor necrosis factor-alpha (TNF-alpha) and, subsequently, transforming growth factor-beta (TGF-beta) signaling networks by PNF1. Here we validate this microarray data set with quantitative real-time polymerase chain reaction (RT-PCR) analysis. Subsequently, we probe this data set and identify three specific TGF-beta-induced genes with regulation by PNF1 conserved over multiple timepoints-amyloid beta (A4) precursor protein (APP), early growth response 1 (EGR-1), and matrix metalloproteinase 14 (MMP14 or MT1-MMP)-that are also implicated in angiogenesis. We further focus on MMP14 given its unique role in angiogenesis, and we validate MT1-MMP modulation by PNF1 with an in vitro fluorescence assay that demonstrates the direct effects that PNF1 exerts on functional metalloproteinase activity. We also utilize endothelial cord formation in collagen gels to show that PNF1-induced stimulation of endothelial cord network formation in vitro is in some way MT1-MMP-dependent. Ultimately, this new network analysis of our transcriptional footprint characterizing PNF1 activity 1-48 h post-supplementation in HMVECs coupled with corresponding validating experiments suggests a key set of a few specific targets that are involved in PNF1 mode of action and important for successful promotion of the neovascularization that we have observed by the drug in vivo.

  10. Inhibitory effects of regorafenib, a multiple tyrosine kinase inhibitor, on corneal neovascularization

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    Halil Ibrahim Onder

    2014-04-01

    Full Text Available AIM:To evaluate the inhibitory effects of regorafenib (BAY 73-4506, a multikinase inhibitor, on corneal neovascularization (NV.METHODS:Thirty adult male Sprague-Dawley rats weighing 250-300 g, were used. Corneal NV was induced by NaOH in the left eyes of each rat. Following the establishment of alkali burn, the animals were randomized into five groups according to topical treatment. Group 1 (n = 6 received 0.9% NaCl, Group 2 (n = 6 received dimethyl sulfoxide, Group 3 (n = 6 received regorafenib 1 mg/mL, Group 4 (n =6 received bevacizumab 5 mg/mL and Group 5 (n = 6 received 0.1% dexamethasone phosphate. On the 7d, the corneal surface covered with neovascular vessels was measured on photographs as the percentage of the cornea’s total area using computer-imaging analysis. The corneas obtained from rats were semiquantitatively evaluated for caspase-3 and vascular endothelial growth factor by immunostaining.RESULTS:A statistically significant difference in the percent area of corneal NV was found among the groups (P <0.001. Although the Group 5 had the smallest percent area of corneal NV, there was no difference among Groups 3, 4 and 5 (P >0.005. There was a statistically significant difference among the groups in apoptotic cell density (P = 0.002. The staining intensity of vascular endothelial growth factor in the epithelial and endothelial layers of cornea was significantly different among the groups (P <0.05. The staining intensity of epithelial and endothelial vascular endothelial growth factor was significantly weaker in Groups 3, 4 and 5 than in Groups 1 and 2.CONCLUSION: Topical administration of regorafenib 1 mg/mL is partly effective for preventing alkali-induced corneal NV in rats.

  11. Nanoparticle-mediated delivery of pioglitazone enhances therapeutic neovascularization in a murine model of hindlimb ischemia.

    Science.gov (United States)

    Nagahama, Ryoji; Matoba, Tetsuya; Nakano, Kaku; Kim-Mitsuyama, Shokei; Sunagawa, Kenji; Egashira, Kensuke

    2012-10-01

    Critical limb ischemia is a severe form of peripheral artery disease (PAD) for which neither surgical revascularization nor endovascular therapy nor current medicinal therapy has sufficient therapeutic effects. Peroxisome proliferator activated receptor-γ agonists present angiogenic activity in vitro; however, systemic administration of peroxisome proliferator-activated receptor-γ agonists is hampered by its side effects, including heart failure. Here, we demonstrate that the nanoparticle (NP)-mediated delivery of the peroxisome proliferator activated receptor-γ agonist pioglitazone enhances its therapeutic efficacy on ischemia-induced neovascularization in a murine model. In a nondiabetic murine model of hindlimb ischemia, a single intramuscular injection of pioglitazone-incorporated NP (1 µg/kg) into ischemic muscles significantly improved the blood flow recovery in the ischemic limbs, significantly increasing the number of CD31-positive capillaries and α-smooth muscle actin-positive arterioles. The therapeutic effects of pioglitazone-incorporated NP were diminished by the peroxisome proliferator activated receptor-γ antagonist GW9662 and were not observed in endothelial NO synthase-deficient mice. Pioglitazone-incorporated NP induced endothelial NO synthase phosphorylation, as demonstrated by Western blot analysis, as well as expression of multiple angiogenic growth factors in vivo, including vascular endothelial growth factor-A, vascular endothelial growth factor-B, and fibroblast growth factor-1, as demonstrated by real-time polymerase chain reaction. Intramuscular injection of pioglitazone (1 µg/kg) was ineffective, and oral administration necessitated a >500 μg/kg per day dose to produce therapeutic effects equivalent to those of pioglitazone-incorporated NP. NP-mediated drug delivery is a novel modality that may enhance the effectiveness of therapeutic neovascularization, surpassing the effectiveness of current treatments for peripheral artery

  12. miR-539-5p inhibits experimental choroidal neovascularization by targeting CXCR7.

    Science.gov (United States)

    Feng, Yifan; Wang, Jing; Yuan, Yuanzhi; Zhang, Xi; Shen, Minqian; Yuan, Fei

    2018-03-01

    Stromal cell-derived factor-1 (SDF-1) has been previously confirmed to participate in the formation of choroidal neovascularization (CNV) via its receptor, CXC chemokine receptor (CXCR) 4; CXCR7 is a recently identified receptor for SDF-1. The molecular mechanisms and therapeutic value of CXCR7 in CNV remain undefined. In this study, experimental CNV was induced by laser photocoagulation in Brown-Norway pigmented rats, and aberrant CXCR7 overexpression was detected in the retinal pigment epithelial/choroid/sclera tissues of laser-injured eyes. Blockade of CXCR7 activation via CXCR7 knockdown or neutralizing Ab administration inhibited SDF-1-induced cell survival and the tubular formation of human retinal microvascular endothelial cells (HRMECs) in vitro and reduced CNV leakage and lesion size in vivo. By using microRNA array screening and bioinformatic analyses, we identified miR-539-5p as a regulator of CXCR7. Transfection of HRMECs and choroid-retinal endothelial (RF/6A) cells with the miR-539-5p mimic inhibited their survival and tube formation, whereas CXCR7 overexpression rescued the suppressive effect of miR-539-5p. The antiangiogenic activities of the miR-539-5p mimic were additionally demonstrated in vivo by intravitreal injection. ERK1/2 and AKT signaling downstream of CXCR7 is involved in the miR-539-5p regulation of endothelial cell behaviors. These findings suggest that the manipulation of miR-539-5p/CXCR7 levels may have important therapeutic implications in CNV-associated diseases.-Feng, Y., Wang, J., Yuan, Y., Zhang, X., Shen, M., Yuan, F. miR-539-5p inhibits experimental choroidal neovascularization by targeting CXCR7.

  13. Study of krypton laser-induced choroidal neovascularization in a Guinea pig model of high anisometropia.

    Science.gov (United States)

    Wang, Jianghui; Jiang, Wei; Kang, Zefeng; Liang, Lina; Liu, Xiaoman; Tian, Nannan; Zhang, Qing

    2012-06-01

    To investigate the association between high anisometropia and the area of choroidal neovascularization (CNV) induced by krypton laser in guinea pigs and better understand the pathogenesis and prevention of myopic CNV. Nine 3-week old male guinea pigs with anisometropia >6.00D were randomly assigned to three groups according to examination date after laser photocoagulation (7d, 14d and 28d). All animals underwent refraction. The eye with higher myopia was used as the experimental eye, and the other as the control eye. All eyes received repeated multi-wavelength krypton laser photocoagulation treatments (wavelength: 532nm; laser power: 400mW; spot diameter: 50μm; exposure time: 0.1s). Fundus photography and indocyanine green angiography (ICGA) were performed. Afterwards, the animals were sacrificed immediately, and the eyes were enucleated and processed for histopathologic examination and flat mounts. CNV appeared at 7d after laser treatment. The area of CNV peaked at 14d, and decrease in area and the presence of scarring was noted at 28 d. CNV was present in 66.7% of eyes by ICGA at 14 d. CNV could be observed under light microscopy at all three time points. At 14d, flat mount showed the neovascular plexus around the lesion. Semi-quantitative analysis revealed that the area of CNV in treated eyes was greater than that of control eyes. Since the mechanism of CNV in this study resembles that of CNV in pathological myopia, this model can be used to investigate the etiology, pathogenesis and treatment of CNV in pathological myopia.

  14. Decellularized Matrix from Tumorigenic Human Mesenchymal Stem Cells Promotes Neovascularization with Galectin-1 Dependent Endothelial Interaction

    Science.gov (United States)

    Burns, Jorge S.; Kristiansen, Malthe; Kristensen, Lars P.; Larsen, Kenneth H.; Nielsen, Maria O.; Christiansen, Helle; Nehlin, Jan; Andersen, Jens S.; Kassem, Moustapha

    2011-01-01

    Background Acquisition of a blood supply is fundamental for extensive tumor growth. We recently described vascular heterogeneity in tumours derived from cell clones of a human mesenchymal stem cell (hMSC) strain (hMSC-TERT20) immortalized by retroviral vector mediated human telomerase (hTERT) gene expression. Histological analysis showed that cells of the most vascularized tumorigenic clone, -BD11 had a pericyte-like alpha smooth muscle actin (ASMA+) and CD146+ positive phenotype. Upon serum withdrawal in culture, -BD11 cells formed cord-like structures mimicking capillary morphogenesis. In contrast, cells of the poorly tumorigenic clone, -BC8 did not stain for ASMA, tumours were less vascularized and serum withdrawal in culture led to cell death. By exploring the heterogeneity in hMSC-TERT20 clones we aimed to understand molecular mechanisms by which mesenchymal stem cells may promote neovascularization. Methodology/Principal Findings Quantitative qRT-PCR analysis revealed similar mRNA levels for genes encoding the angiogenic cytokines VEGF and Angiopoietin-1 in both clones. However, clone-BD11 produced a denser extracellular matrix that supported stable ex vivo capillary morphogenesis of human endothelial cells and promoted in vivo neovascularization. Proteomic characterization of the -BD11 decellularized matrix identified 50 extracellular angiogenic proteins, including galectin-1. siRNA knock down of galectin-1 expression abrogated the ex vivo interaction between decellularized -BD11 matrix and endothelial cells. More stable shRNA knock down of galectin-1 expression did not prevent -BD11 tumorigenesis, but greatly reduced endothelial migration into -BD11 cell xenografts. Conclusions Decellularized hMSC matrix had significant angiogenic potential with at least 50 angiogenic cell surface and extracellular proteins, implicated in attracting endothelial cells, their adhesion and activation to form tubular structures. hMSC -BD11 surface galectin-1 expression was

  15. External beam radiotherapy for subretinal neovascularization in age-related macular degeneration: is this treatment efficient?

    International Nuclear Information System (INIS)

    Staar, Susanne; Krott, Ralf; Mueller, Rolf-Peter; Bartz-Schmidt, Karl U.; Heimann, Klaus

    1999-01-01

    Purpose: Control of the natural course of sub retinal neovascularization (SRNV) in age-related macular degeneration (AMD) is difficult. Only a subset of patients is suitable for laser coagulation. This prospective study aimed to determine the efficacy and individual benefit of external beam radiotherapy (EBRT). Methods and Materials: The prospective trial included 287 patients with subfoveal neovascularization due to AMD which was verified by fluorescein angiography. Patients have been treated between January 1996 and October 1997. All patients received a total dose of 16 Gy in 2-Gy daily fractions with 5-6 MeV photons based on computerized treatment planning in individual head mask fixation. This first analysis is based on 73 patients (50 women, 23 men, median age 74.3 years), with a median follow-up of 13.3 months and a minimum follow-up of 11 months. Results: All patients completed therapy and tolerability was good. First clinical control with second angiography was performed 6 weeks after irradiation, then in 3-month intervals. Eighteen patients with SRNV refusing radiotherapy served as a control group and were matched with 18 irradiated patients. After 7 months median visual acuity (VA) was 20/160 for the irradiated and 20/400 for the untreated patients. One year after radiotherapy final median VA was 20/400 in both groups. Conclusion: These results suggest that 16 Gy of conventionally fractionated external beam irradiation slows down the visual loss in exudative AMD for only a few months. Patients' reading vision could not be saved for a long-term run

  16. Transscleral sustained vasohibin-1 delivery by a novel device suppressed experimentally-induced choroidal neovascularization.

    Directory of Open Access Journals (Sweden)

    Hideyuki Onami

    Full Text Available We established a sustained vasohibin-1 (a 42-kDa protein, delivery device by a novel method using photopolymerization of a mixture of polyethylene glycol dimethacrylate, triethylene glycol dimethacrylate, and collagen microparticles. We evaluated its effects in a model of rat laser-induced choroidal neovascularization (CNV using a transscleral approach. We used variable concentrations of vasohibin-1 in the devices, and used an enzyme-linked immunosorbent assay and Western blotting to measure the released vasohibin-1 (0.31 nM/day when using the 10 μM vasohibin-1 delivery device [10VDD]. The released vasohibin-1 showed suppression activity comparable to native effects when evaluated using endothelial tube formation. We also used pelletized vasohibin-1 and fluorescein isothiocyanate-labeled 40 kDa dextran as controls. Strong fluorescein staining was observed on the sclera when the device was used for drug delivery, whereas pellet use produced strong staining in the conjunctiva and surrounding tissue, but not on the sclera. Vasohibin-1 was found in the sclera, choroid, retinal pigment epithelium (RPE, and neural retina after device implantation. Stronger immunoreactivity at the RPE and ganglion cell layers was observed than in other retinal regions. Significantly lower fluorescein angiography (FA scores and smaller CNV areas in the flat mounts of RPE-choroid-sclera were observed for the 10VDD, VDD (1 μM vasohibin-1 delivery device, and vasohibin-1 intravitreal direct injection (0.24 μM groups when compared to the pellet, non-vasohibin-1 delivery device, and intravitreal vehicle injection groups. Choroidal neovascularization can be treated with transscleral sustained protein delivery using our novel device. We offer a safer sustained protein release for treatment of retinal disease using the transscleral approach.

  17. Anti-vascular endothelial growth factor therapy for the treatment of myopic choroidal neovascularization

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    Tan CS

    2017-09-01

    Full Text Available Colin S Tan,1,2 SriniVas R Sadda3 1National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore; 2Fundus Image Reading Center, National Healthcare Group Eye Institute, Singapore; 3Doheny Eye Institute, University of California Los Angeles, CA, USA Abstract: Myopic choroidal neovascularization (CNV is a sight-threatening condition which occurs in eyes with myopia, particularly in those with pathologic myopia. It is the most common cause of CNV among patients younger than 50 years. Hemorrhage and exudation from the CNV lesion may eventually result in scarring or chorioretinal atrophy. While myopic CNV was previously treated with focal laser photocoagulation or photodynamic therapy (PDT, the current treatment of choice is anti-vascular endothelial growth factor (VEGF agents. Many studies have demonstrated the efficacy of intravitreal anti-VEGF agents in the treatment of myopic CNV. The RADIANCE study reported that intravitreal ranibizumab was superior to PDT in eyes with myopic CNV (at 3 months, both groups receiving intravitreal ranibizumab gained 10.5 and 10.6 letters vs 2.2 letters among patients receiving PDT. In addition, the study demonstrated similar visual outcomes in eyes treated on the basis of visual acuity stabilization or disease activity criteria. Other clinical studies have provided evidence for the efficacy of ranibizumab and aflibercept in the treatment of myopic CNV. This review addresses the epidemiology, pathophysiology, and imaging characteristics of myopic CNV, and discusses the evidence for the efficacy of anti-VEGF agents as compared to laser photocoagulation and PDT. Keywords: myopic choroidal neovascularization, ranibizumab, anti-vascular endothelial growth factor

  18. Optical Coherence Tomography and the Development of Antiangiogenic Therapies in Neovascular Age-Related Macular Degeneration

    Science.gov (United States)

    Rosenfeld, Philip J.

    2016-01-01

    Purpose To explain the pivotal role optical coherence tomography (OCT) imaging had in the development of antiangiogenic therapies for the treatment of neovascular age-related macular degeneration (nvAMD). Methods A historical literature review was combined with personal perspectives from the introduction of OCT imaging and the early clinical use of vascular endothelial growth factor (VEGF) inhibitors. Results At the time that OCT emerged, the gold standard for imaging of nvAMD was fluorescein angiography (FA), a time-consuming, dye-based, invasive technique that provided en face images of the retina and was used to characterize leakage, perfusion status, and the types of macular neovascularization (MNV). In comparison, OCT imaging was a fast, safe, noninvasive technique that complemented FA imaging by providing cross-sectional images of the macula. OCT was able to visualize and quantify the macular fluid that was associated with the presence of excess VEGF, which was identified by intraretinal fluid, subretinal fluid, and fluid under the retinal pigment epithelium (RPE). Clinicians quickly appreciated the benefits of OCT imaging for following macular fluid after anti-VEGF therapy. By observing the qualitative and quantitative changes in macular fluid depicted by OCT imaging, clinicians were empowered to compare anti-VEGF drugs and move from fixed-dosing regimens to patient-specific dosing strategies requiring fewer injections. Conclusions Optical coherence tomography imaging was adopted as a VEGF-meter, a method to detect excess VEGF, and evolved to become the gold standard imaging strategy for diagnosing nvAMD, assessing treatment responses to anti-VEGF drugs, deciding when to re-treat, and evaluating disease progression. PMID:27409464

  19. Luminal progenitors restrict their lineage potential during mammary gland development.

    Science.gov (United States)

    Rodilla, Veronica; Dasti, Alessandro; Huyghe, Mathilde; Lafkas, Daniel; Laurent, Cécile; Reyal, Fabien; Fre, Silvia

    2015-02-01

    The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes.

  20. Reporter-Based Isolation of Developmental Myogenic Progenitors

    Directory of Open Access Journals (Sweden)

    Eyemen Kheir

    2018-04-01

    Full Text Available The formation and activity of mammalian tissues entail finely regulated processes, involving the concerted organization and interaction of multiple cell types. In recent years the prospective isolation of distinct progenitor and stem cell populations has become a powerful tool in the hands of developmental biologists and has rendered the investigation of their intrinsic properties possible. In this protocol, we describe how to purify progenitors with different lineage history and degree of differentiation from embryonic and fetal skeletal muscle by fluorescence-activated cell sorting (FACS. The approach takes advantage of a panel of murine strains expressing fluorescent reporter genes specifically in the myogenic progenitors. We provide a detailed description of the dissection procedures and of the enzymatic dissociation required to maximize the yield of mononucleated cells for subsequent FACS-based purification. The procedure takes ~6–7 h to complete and allows for the isolation and the subsequent molecular and phenotypic characterization of developmental myogenic progenitors.

  1. Endothelial progenitor cells in chronic obstructive pulmonary disease and emphysema

    Science.gov (United States)

    Tracy, Russell P.; Parikh, Megha A.; Hoffman, Eric A.; Shimbo, Daichi; Austin, John H. M.; Smith, Benjamin M.; Hueper, Katja; Vogel-Claussen, Jens; Lima, Joao; Gomes, Antoinette; Watson, Karol; Kawut, Steven; Barr, R. Graham

    2017-01-01

    Endothelial injury is implicated in the pathogenesis of COPD and emphysema; however the role of endothelial progenitor cells (EPCs), a marker of endothelial cell repair, and circulating endothelial cells (CECs), a marker of endothelial cell injury, in COPD and its subphenotypes is unresolved. We hypothesized that endothelial progenitor cell populations would be decreased in COPD and emphysema and that circulating endothelial cells would be increased. Associations with other subphenotypes were examined. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50–79 years without clinical cardiovascular disease. Endothelial progenitor cell populations (CD34+KDR+ and CD34+KDR+CD133+ cells) and circulating endothelial cells (CD45dimCD31+CD146+CD133-) were measured by flow cytometry. COPD was defined by standard spirometric criteria. Emphysema was assessed qualitatively and quantitatively on CT. Full pulmonary function testing and expiratory CTs were measured in a subset. Among 257 participants, both endothelial progenitor cell populations, and particularly CD34+KDR+ endothelial progenitor cells, were reduced in COPD. The CD34+KDR+CD133+ endothelial progenitor cells were associated inversely with emphysema extent. Both endothelial progenitor cell populations were associated inversely with extent of panlobular emphysema and positively with diffusing capacity. Circulating endothelial cells were not significantly altered in COPD but were inversely associated with pulmonary microvascular blood flow on MRI. There was no consistent association of endothelial progenitor cells or circulating endothelial cells with measures of gas trapping. These data provide evidence that endothelial repair is impaired in COPD and suggest that this pathological process is specific to emphysema. PMID:28291826

  2. Liver sinusoidal endothelial cells induce immunosuppressive IL-10-producing Th1 cells via the Notch pathway

    NARCIS (Netherlands)

    Neumann, Katrin; Rudolph, Christine; Neumann, Christian; Janke, Marko; Amsen, Derk; Scheffold, Alexander

    2015-01-01

    Under homeostasis, liver sinusoidal endothelial cells (LSECs) shift intrahepatic T-cell responses towards tolerance. However, the role of LSECs in the regulation of T-cell-induced liver inflammation is less clear. Here, we studied the capacity of LSECs to modulate pro-inflammatory Th1-cell

  3. Invited review: mesenchymal progenitor cells in intramuscular connective tissue development.

    Science.gov (United States)

    Miao, Z G; Zhang, L P; Fu, X; Yang, Q Y; Zhu, M J; Dodson, M V; Du, M

    2016-01-01

    The abundance and cross-linking of intramuscular connective tissue contributes to the background toughness of meat, and is thus undesirable. Connective tissue is mainly synthesized by intramuscular fibroblasts. Myocytes, adipocytes and fibroblasts are derived from a common pool of progenitor cells during the early embryonic development. It appears that multipotent mesenchymal stem cells first diverge into either myogenic or non-myogenic lineages; non-myogenic mesenchymal progenitors then develop into the stromal-vascular fraction of skeletal muscle wherein adipocytes, fibroblasts and derived mesenchymal progenitors reside. Because non-myogenic mesenchymal progenitors mainly undergo adipogenic or fibrogenic differentiation during muscle development, strengthening progenitor proliferation enhances the potential for both intramuscular adipogenesis and fibrogenesis, leading to the elevation of both marbling and connective tissue content in the resulting meat product. Furthermore, given the bipotent developmental potential of progenitor cells, enhancing their conversion to adipogenesis reduces fibrogenesis, which likely results in the overall improvement of marbling (more intramuscular adipocytes) and tenderness (less connective tissue) of meat. Fibrogenesis is mainly regulated by the transforming growth factor (TGF) β signaling pathway and its regulatory cascade. In addition, extracellular matrix, a part of the intramuscular connective tissue, provides a niche environment for regulating myogenic differentiation of satellite cells and muscle growth. Despite rapid progress, many questions remain in the role of extracellular matrix on muscle development, and factors determining the early differentiation of myogenic, adipogenic and fibrogenic cells, which warrant further studies.

  4. LINKING TYPE Ia SUPERNOVA PROGENITORS AND THEIR RESULTING EXPLOSIONS

    International Nuclear Information System (INIS)

    Foley, Ryan J.; Kirshner, Robert P.; Simon, Joshua D.; Burns, Christopher R.; Gal-Yam, Avishay; Hamuy, Mario; Morrell, Nidia I.; Phillips, Mark M.; Shields, Gregory A.; Sternberg, Assaf

    2012-01-01

    Comparing the ejecta velocities at maximum brightness and narrow circumstellar/interstellar Na D absorption line profiles of a sample of 23 Type Ia supernovae (SNe Ia), we determine that the properties of SN Ia progenitor systems and explosions are intimately connected. As demonstrated by Sternberg et al., half of all SNe Ia with detectable Na D absorption at the host-galaxy redshift in high-resolution spectroscopy have Na D line profiles with significant blueshifted absorption relative to the strongest absorption component, which indicates that a large fraction of SN Ia progenitor systems have strong outflows. In this study, we find that SNe Ia with blueshifted circumstellar/interstellar absorption systematically have higher ejecta velocities and redder colors at maximum brightness relative to the rest of the SN Ia population. This result is robust at a 98.9%-99.8% confidence level, providing the first link between the progenitor systems and properties of the explosion. This finding is further evidence that the outflow scenario is the correct interpretation of the blueshifted Na D absorption, adding additional confirmation that some SNe Ia are produced from a single-degenerate progenitor channel. An additional implication is that either SN Ia progenitor systems have highly asymmetric outflows that are also aligned with the SN explosion or SNe Ia come from a variety of progenitor systems where SNe Ia from systems with strong outflows tend to have more kinetic energy per unit mass than those from systems with weak or no outflows.

  5. Corneal Neovascularization with Associated Lipid Keratopathy in a Patient with Obstructive Sleep Apnea-Hypopnea Syndrome Using a Continuous Positive Airway Pressure Machine

    Directory of Open Access Journals (Sweden)

    Konstantinos Oikonomakis

    2017-08-01

    Full Text Available Objective: To report a case of corneal neovascularization with secondary lipid keratopathy in a patient treated with continuous positive airway pressure (CPAP for obstructive sleep apnea-hypopnea syndrome (OSAHS. Case Report: A 49-year-old male had been diagnosed with obstructive sleep apnea syndrome 10 years ago and has been treated with the application of a CPAP machine during night sleep ever since. For the past year, the patient had been complaining for ocular irritation and excessive tearing of the left eye on awakening. Slit-lamp biomicroscopy revealed the presence of neovascularization and lipid exudation in the inferior third of the cornea of the left eye. Ocular patching during night sleep resulted in recession of the reported symptoms and shrinkage of the neovascularization, while the area of lipid exudation ceased to enlarge. Conclusion: To the best of our knowledge, this is the first report of corneal neovascularization in a patient using a CPAP machine for OSAHS.

  6. Corneal Neovascularization with Associated Lipid Keratopathy in a Patient with Obstructive Sleep Apnea-Hypopnea Syndrome Using a Continuous Positive Airway Pressure Machine.

    Science.gov (United States)

    Oikonomakis, Konstantinos; Petrelli, Myrsini; Andreanos, Konstantinos; Mouchtouris, Andreas; Petrou, Petros; Georgalas, Ilias; Papaconstantinou, Dimitrios; Kymionis, George

    2017-01-01

    To report a case of corneal neovascularization with secondary lipid keratopathy in a patient treated with continuous positive airway pressure (CPAP) for obstructive sleep apnea-hypopnea syndrome (OSAHS). A 49-year-old male had been diagnosed with obstructive sleep apnea syndrome 10 years ago and has been treated with the application of a CPAP machine during night sleep ever since. For the past year, the patient had been complaining for ocular irritation and excessive tearing of the left eye on awakening. Slit-lamp biomicroscopy revealed the presence of neovascularization and lipid exudation in the inferior third of the cornea of the left eye. Ocular patching during night sleep resulted in recession of the reported symptoms and shrinkage of the neovascularization, while the area of lipid exudation ceased to enlarge. To the best of our knowledge, this is the first report of corneal neovascularization in a patient using a CPAP machine for OSAHS.

  7. Aflibercept: a review of its use in the treatment of choroidal neovascularization due to age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Balaratnasingam C

    2015-12-01

    Full Text Available Chandrakumar Balaratnasingam,1–3 Elona Dhrami-Gavazi,1,2,4 Jesse T McCann,1,2,4,5 Quraish Ghadiali,1,2 K Bailey Freund1,2,4,5 1Vitreous-Retina-Macula Consultants of New York, NY, USA; 2LuEsther T Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, NY, USA; 3Centre for Ophthalmology and Visual Sciences, Lions Eye Institute, University of Western Australia, Perth, WA, Australia; 4Department of Ophthalmology, Edward S Harkness Eye Institute, Columbia University College of Physicians and Surgeons, New York, NY, USA; 5Department of Ophthalmology, New York University School of Medicine, New York, NY, USA Abstract: Choroidal neovascularization (CNV due to age-related macular degeneration (AMD is an important cause of visual morbidity globally. Modern treatment strategies for neovascular AMD achieve regression of CNV by suppressing the activity of key growth factors that mediate angiogenesis. Vascular endothelial growth factor (VEGF has been the major target of neovascular AMD therapy for almost two decades, and there have been several intravitreally-administered agents that have enabled anatomical restitution and improvement in visual function with continual dosing. Aflibercept (EYLEA®, initially named VEGF Trap-eye, is the most recent anti-VEGF agent to be granted US Food and Drug Administration approval for the treatment of neovascular AMD. Biologic advantages of aflibercept include its greater binding affinity for VEGF, a longer intravitreal half-life relative to other anti-VEGF agents, and the capacity to antagonize growth factors other than VEGF. This paper provides an up-to-date summary of the molecular mechanisms mediating CNV. The structural, pharmacodynamic, and pharmacokinetic advantages of aflibercept are also reviewed to rationalize the utility of this agent for treating CNV. Results of landmark clinical investigations, including VIEW 1 and 2 trials, and other important studies are then summarized and used to

  8. Clues on Type Ia Supernovae Progenitors

    International Nuclear Information System (INIS)

    Piersanti, Luciano; Tornambe, Amedeo

    2005-01-01

    We show that in the framework of canonical stellar evolution it is hard, if not impossible, to determine the growth in mass of a CO White Dwarf, up to the Chandrasekhar limit by means of mass transfer from its companion in a binary system. This is the case either if matter is accreted from a normal companion with an H-rich envelope or if direct CO accretion occurs from a CO WD companion. At variance, we show that if the effects of rotation are taken into account in modeling the accretion process, a CO WD can increase its mass at the expenses of the degenerate CO companion up and beyond 1.4 M· , so that an explosive event of the type Ia class is naturally produced. This theoretical finding revives the Double Degenerate scenario for type Ia SNe progenitors. In such a case the internal spread in the observational properties of type Ia SNe may be interpreted as a consequence of different total masses; hence differences between SNe Ia in nearby elliptical galaxies and the majority of those in spirals should be expected and the current use of type Ia SNe as cosmological distance indicators should be justified

  9. TWEAK induces liver progenitor cell proliferation

    Science.gov (United States)

    Jakubowski, Aniela; Ambrose, Christine; Parr, Michael; Lincecum, John M.; Wang, Monica Z.; Zheng, Timothy S.; Browning, Beth; Michaelson, Jennifer S.; Baestcher, Manfred; Wang, Bruce; Bissell, D. Montgomery; Burkly, Linda C.

    2005-01-01

    Progenitor (“oval”) cell expansion accompanies many forms of liver injury, including alcohol toxicity and submassive parenchymal necrosis as well as experimental injury models featuring blocked hepatocyte replication. Oval cells can potentially become either hepatocytes or biliary epithelial cells and may be critical to liver regeneration, particularly when hepatocyte replication is impaired. The regulation of oval cell proliferation is incompletely understood. Herein we present evidence that a TNF family member called TWEAK (TNF-like weak inducer of apoptosis) stimulates oval cell proliferation in mouse liver through its receptor Fn14. TWEAK has no effect on mature hepatocytes and thus appears to be selective for oval cells. Transgenic mice overexpressing TWEAK in hepatocytes exhibit periportal oval cell hyperplasia. A similar phenotype was obtained in adult wild-type mice, but not Fn14-null mice, by administering TWEAK-expressing adenovirus. Oval cell expansion induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) was significantly reduced in Fn14-null mice as well as in adult wild-type mice with a blocking anti-TWEAK mAb. Importantly, TWEAK stimulated the proliferation of an oval cell culture model. Finally, we show increased Fn14 expression in chronic hepatitis C and other human liver diseases relative to its expression in normal liver, which suggests a role for the TWEAK/Fn14 pathway in human liver injury. We conclude that TWEAK has a selective mitogenic effect for liver oval cells that distinguishes it from other previously described growth factors. PMID:16110324

  10. Harmine stimulates proliferation of human neural progenitors

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    Vanja Dakic

    2016-12-01

    Full Text Available Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A, which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY, and an irreversible selective inhibitor of monoamine oxidase (MAO but not DYRK1A (pargyline. INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo.

  11. Hepatic progenitors for liver disease: current position

    Directory of Open Access Journals (Sweden)

    Alice Conigliaro

    2010-02-01

    Full Text Available Alice Conigliaro1, David A Brenner2, Tatiana Kisseleva21University “La Sapienza”, Dipartimento di Biotecnologie Cellulari ed Ematologia Policlinico Umberto I, V Clinica Medica, Rome, Italy; 2Department of Medicine, University of California, San Diego, La Jolla, CA, USAAbstract: Liver regeneration restores the original functionality of hepatocytes and cholangiocytes in response to injury. It is regulated on several levels, with different cellular populations contributing to this process, eg, hepatocytes, liver precursor cells, intrahepatic stem cells. In response to injury, mature hepatocytes have the capability to proliferate and give rise to new hepatocytes and cholangiocytes. Meanwhile, liver precursor cells (oval cells have become the most recognized bipotential precursor cells in the damaged liver. They rapidly proliferate, change their cellular composition, and differentiate into hepatocytes and cholangiocytes to compensate for the cellular loss and maintain liver homeostasis. There is a growing body of evidence that oval cells originate from the intrahepatic stem cell(s, which in turn give(s rise to epithelial, including oval cells, and/or other hepatic cells of nonepithelial origin. Since there is a close relationship between the liver and hematopoiesis, bone marrow derived cells can also contribute to liver regeneration by the fusion of myeloid cells with damaged hepatocytes, or differentiation of mesenchymal stem cells into hepatocyte-like cells. The current review discusses the contribution of different cells to liver regeneration and their characteristics.Keywords: hepatic progenitor, liver disease, liver precursor cells, oval cells, hepatocytes, intrahepatic stem cells, cholangiocytes

  12. Targeted ablation of Crb2 in photoreceptor cells induces retinitis pigmentosa

    NARCIS (Netherlands)

    Alves, Celso Henrique; Pellissier, Lucie P; Vos, Rogier M; Garcia Garrido, Marina; Sothilingam, Vithiyanjali; Seide, Christina; Beck, Susanne C; Klooster, J.; Furukawa, Takahisa; Flannery, John G; Verhaagen, J.; Seeliger, Mathias W; Wijnholds, J.

    2014-01-01

    In humans, the Crumbs homolog-1 (CRB1) gene is mutated in autosomal recessive Leber congenital amaurosis and early-onset retinitis pigmentosa. In mammals, the Crumbs family is composed of: CRB1, CRB2, CRB3A and CRB3B. Recently, we showed that removal of mouse Crb2 from retinal progenitor cells, and

  13. Long-Term Visual Outcomes for a Treat and Extend Anti-Vascular Endothelial Growth Factor Regimen in Eyes with Neovascular Age-Related Macular Degeneration

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    Sarah Mrejen

    2015-07-01

    Full Text Available With the advent of anti-vascular endothelial growth factor (VEGF therapy, clinicians are now focused on various treatment strategies to better control neovascular age-related macular degeneration (NVAMD, a leading cause of irreversible blindness. Herein, we retrospectively reviewed consecutive patients with treatment-naïve NVAMD initially classified based on fluorescein angiography (FA alone or with an anatomic classification utilizing both FA and optical coherence tomography (OCT and correlated long-term visual outcomes of these patients treated with an anti-VEGF Treat-and-Extend Regimen (TER with baseline characteristics including neovascular phenotype. Overall, 185 patients (210 eyes were followed over an average of 3.5 years (range 1–6.6 with a retention rate of 62.9%, and visual acuity significantly improved with a TER that required a mean number of 8.3 (±1.6 (± standard deviation intravitreal anti-VEGF injections/year (range 4–13. The number of injections and the anatomic classification were independent predictors of visual acuity at 6 months, 1, 2, 3 and 4 years. Patients with Type 1 neovascularization had better visual outcomes and received more injections than the other neovascular subtypes. There were no serious adverse events. A TER provided sustained long-term visual gains. Eyes with Type 1 neovascularization had better visual outcomes than those with other neovascular subtypes.

  14. Relapse of choroidal neovascularization in Bietti's crystalline retinopathy following anti-vascular endothelial growth factor therapy: A case report.

    Science.gov (United States)

    Hua, Rui; Chen, Kang; Hu, Yuedong; Wang, Xinling; Chen, Lei

    2015-11-01

    Choroidal neovascularization secondary to retinitis pigmentosa is rarely observed in clinical practice. The present study describes a case of atypical retinitis pigmentosa, crystalline retinal pigmentary degeneration, complicated by choroidal neovascularization (CNV) in a 26-year-old man presenting with blurred vision in the right eye. Heidelberg multimodality imaging was performed to achieve a confirmed diagnosis. Bevacizumab was injected once intravitreally. The 3-month follow-up included visualization of the lesion's regression with spectral domain optical coherence tomography (SD-OCT). However, at 3 months after the injection, the CNV reoccurred. To the best of our knowledge, this is the first time that a case of CNV secondary to retinitis pigmentosa, in which the diagnosis was confirmed via multimodality imaging and the therapeutic efficacy was evaluated by SD-OCT, has been reported in China.

  15. Effects of nuclear factor κB expression on retinal neovascularization and apoptosis in a diabetic retinopathy rat model

    Institute of Scientific and Technical Information of China (English)

    Ning; Jiang; Xiao-Long; Chen; Hong-Wei; Yang; Yu-Ru; Ma

    2015-01-01

    AIM: To investigate the expression and role of nuclear factor κB(NF-κB) in diabetic retinopathy(DR) and its relationship with neovascularization and retinal cell apoptosis. METHODS: A total of 80 male Wistar rats were randomly assigned to control(4, 8, 12 and 16 wk, n =10 in each group) and diabetes mellitus(DM) groups(4, 8, 12 and 16wk, n =10 in each group). A diabetic rat model was established by intraperitoneal injection of streptozotocin(60 mg/kg). After 4, 8, 12 and 16 wk, rats were sacrificed.Retinal layers and retinal neovascularization growth were stained with hematoxylin-eosin and examined under light microscopy. Cell apoptosis in the retina was detected by Td T-mediated d UTP nick end labeling, and NF-κB distribution and expression in the retina was determined using immunohistochemistry. RESULTS: DM model success rate up to 100%.Diabetes model at each time point after the experimental groupcompared with the control group, the blood glucose was significantly increased, decreased body weight, each time point showed significant differences compared with the control group(P <0.01). After 12 wk other pathological changes in the retina of diabetic rats were observed; after 16 wk, neovascularization were observed. After 1mo, retinal cell apoptosis was observed.Compared with the control group, NF-κB expression in the DM group significantly increased with disease duration.CONCLUSION: With the prolonging of DM progression,the expression NF-κB increases. NF-κB may be related to retinal cell apoptosis and neovascularization.

  16. Short-term outcomes after EX-PRESS implantation versus trabeculectomy alone in patients with neovascular glaucoma

    OpenAIRE

    Shinohara, Yoichiro; Akiyama, Hideo; Magori, Mikiya; Kishi, Shoji

    2017-01-01

    Yoichiro Shinohara, Hideo Akiyama, Mikiya Magori, Shoji Kishi Department of Ophthalmology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan Background: The purpose of this study was to investigate postoperative clinical outcomes in patients with neovascular glaucoma (NVG) who underwent trabeculectomy or EX-PRESS implantation and to identify predictors of successful EX-PRESS implantation. Methods: The study designed as a retrospective observational analysis and was set in...

  17. Worsening anatomic outcomes following aflibercept for neovascular age-related macular degeneration in eyes previously well controlled with ranibizumab

    Directory of Open Access Journals (Sweden)

    Nudleman E

    2016-06-01

    Full Text Available Eric Nudleman,1 Jeremy D Wolfe,2,3 Maria A Woodward,4 Yoshihiro Yonekawa,2,3 George A Williams,2,3 Tarek S Hassan2,3 1Department of Ophthalmology, Shiley Eye Center, University of California, San Diego, La Jolla, CA, 2Beaumont Eye Institute, Oakland University William Beaumont School of Medicine, 3Associated Retinal Consultants, Royal Oak, 4Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, MI, USA Purpose: Antivascular endothelial growth factor injection is the mainstay of treating neovascular age-related macular degeneration (AMD. Previous studies have shown that switching treatment from ranibizumab to aflibercept led to an improvement in eyes with recalcitrant activity. Herein, we identify a unique subset of patients whose eyes with neovascular AMD were previously well controlled with ranibizumab injections were then worsened after being switched to aflibercept. Methods: This is a retrospective interventional case series. Eyes with neovascular AMD, previously well controlled with monthly injections of ranibizumab, which then developed worsening of subretinal fluid after being switched to aflibercept were included. Results: A total of 17 eyes were included. All eyes developed increased subretinal fluid when switched from ranibizumab to aflibercept. Fourteen patients were switched back to ranibizumab after a single injection of aflibercept and had subsequent rapid resolution of subretinal fluid. Three patients continued with monthly aflibercept injections for two subsequent months and demonstrated the persistence of the increased subretinal fluid until they were switched back to treatment with ranibizumab at which time the fluid resolved. No eye had persistent decline in visual acuity. Conclusion: Switching from intravitreal ranibizumab to aflibercept in eyes with well-controlled neovascular AMD may result in worsening in a subset of patients and resolves when therapy is switched back to ranibizumab. Keywords: anti

  18. Intravitreal bevacizumab has initial clinical benefit lasting eight weeks in eyes with neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    P William Conrad

    2008-06-01

    Full Text Available P William Conrad, David N Zacks, Mark W JohnsonDepartment of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, USAPurpose: To determine whether the effect of a single initial intravitreal injection of bevacizumab for neovascular age-related macular degeneration (AMD persists for 8 weeks.Methods: We reviewed the records of 25 consecutive patients with neovascular AMD treated with intravitreal bevacizumab. Patients were included (n = 15 if follow up data were available from 4 and 8 week visits after a single initial injection. Additionally, optical coherence tomography (OCT images were graded qualitatively in a masked fashion by a single reader.Results: Baseline mean visual acuity was 20/200, improving to 20/125 at 4 weeks (p = 0.0153 and 20/100 at 8 weeks (p = 0.0027. Mean central retinal thickness was 316 ± 107 µm at baseline and decreased to 223 ± 70 µm and 206 ± 45 µm at 4 and 8 weeks post-injection, respectively (p = 0.0003 and 0.0005. By masked OCT grading, macular fluid was resolved in 10/15 (66.7% and 11/15 (73.3% eyes at 4 and 8 weeks, respectively, and 3/15 (20% eyes had continued reduction in residual macular fluid between 4 and 8 weeks.Conclusions: A single initial bevacizumab injection has persistent clinical benefit lasting 8 weeks in most eyes with neovascular AMD. Results of prospective randomized studies are needed before changes in treatment regimens can be recommended.Keywords: age-related macular degeneration, bevacizumab, choroidal neovascular membrane, optical coherence tomography

  19. Use of Adipose-Derived Mesenchymal Stem Cells to Accelerate Neovascularization in Interpolation Flaps.

    Science.gov (United States)

    Izmirli, Hakki Hayrettin; Alagoz, Murat Sahin; Gercek, Huseyin; Eren, Guler Gamze; Yucel, Ergin; Subasi, Cansu; Isgoren, Serkan; Muezzinoglu, Bahar; Karaoz, Erdal

    2016-01-01

    Interpolation flaps are commonly used in plastic surgery to cover wide and deep defects. The need to, wait for 2 to 3 weeks until the division of the pedicle still, however, poses a serious challenge, not only extending treatment and hospital stay, but also increasing hospital expenses. To solve this problem, we have aimed to use the angiogenic potential of stem cells to selectively accelerate neovascularization with a view to increasing the viability of interpolation flaps and achieving early pedicle removal. A total of 32 rats were allocated to 2 groups as control (N = 16) and experiment (N = 16). The cranial flaps 6 × 5 cm in size located on the back of the rats were raised. Then, a total suspension containing 3 × 10(6) adipose-derived mesenchymal stem cells (ADSC) tagged with a green fluorescent protein (GFP) was injected diffusely into the distal part of the flap, receiving bed, and wound edges. In the control group, only a medium solution was injected into the same sites. After covering the 3 × 5 cm region in the proximal part of the area where the flap was removed, the distal part of the flap was adapted to the uncovered distal area. The pedicles of 4 rats in each group were divided on postoperative days 5, 8, 11, and 14. The areas were photographed 7 days after the pedicles were released. The photographs were processed using Adobe Acrobat 9 Pro software (San Jose, CA) to measure the flap survival area in millimeters and to compare groups. Seven days after the flap pedicle was divided, the rats were injected with 250 mCi Tc-99 mm (methoxy-isobutyl-isonitrie) from the penile vein, and scintigraphic images were obtained. The images obtained from each group were subjected to a numerical evaluation, which was then used in the comparison between groups. The flaps were then examined by histology to numerically compare the number of newly formed vessels. Neovascularization was also assessed by microangiography. In addition, radiographic images were obtained by

  20. Multi-scale osteointegration and neovascularization of biphasic calcium phosphate bone scaffolds

    Science.gov (United States)

    Lan, Sheeny K.

    Bone grafts are utilized clinically to guide tissue regeneration. Autologous bone and allogeneic bone are the current clinical standards. However, there are significant limitations to their use. To address the need for alternatives to autograft and allograft, researchers have worked to develop synthetic grafts, also referred to as scaffolds. Despite extensive efforts in this area, a gap persists between basic research and clinical application. In particular, solutions for repairing critical size and/or load-bearing defects are lacking. The aim of this thesis work was to address two critical barriers preventing design of successful tissue engineering constructs for bone regeneration within critical size and/or load-bearing defects. Those barriers are insufficient osteointegration and slow neovascularization. In this work, the effects of scaffold microporosity, recombinant human bone morphogenetic protein-2 delivery and endothelial colony forming cell vasculogenesis were evaluated in the context of bone formation in vivo. This was accomplished to better understand the role of these factors in bone regeneration, which may translate to improvements in tissue engineering construct design. Biphasic calcium phosphate (BCP) scaffolds with controlled macro- and microporosity were implanted in porcine mandibular defects. Evaluation of the BCP scaffolds after in vivo implantation showed, for the first time, osteocytes embedded in bone within scaffold micropores (macro and micro length scales, leaving no "dead space" or discontinuities of bone in the defect site. The scaffold forms a living composite upon integration with regenerating bone and this has significant implications with regard to improved scaffold mechanical properties. The presence of osteocytes within scaffold micropores is an indication of scaffold osteoinductivity because a chemotactic factor must be present to induce cell migration into pores on the order of the cell diameter. It is likely that the scaffold

  1. Effect of trapping vascular endothelial growth factor-A in a murine model of dry eye with inflammatory neovascularization.

    Science.gov (United States)

    Kwon, Jin Woo; Choi, Jin A; Shin, Eun Young; La, Tae Yoon; Jee, Dong Hyun; Chung, Yeon Woong; Cho, Yang Kyung

    2016-01-01

    To evaluate whether trapping vascular endothelial growth factor A (VEGF-A) would suppress angiogenesis and inflammation in dry eye corneas in a murine corneal suture model. We established two groups of animals, one with non-dry eyes and the other with induced dry eyes. In both groups, a corneal suture model was used to induce inflammation and neovascularization. Each of two groups was again divided into three subgroups according to the treatment; subgroup I (aflibercept), subgroup II (dexamethasone) and subgroup III (phosphate buffered saline, PBS). Corneas were harvested and immunohistochemical staining was performed to compare the extents of neovascularization and CD11b+ cell infiltration. Real-time polymerase chain reaction was performed to quantify the expression of inflammatory cytokines and VEGF-A in the corneas. Trapping VEGF-A with aflibercept resulted in significantly decreased angiogenesis and inflammation compared with the dexamethasone and PBS treatments in the dry eye corneas (all P dry eyes. The anti-inflammatory and anti-angiogenic effects of VEGF-A trapping were stronger than those of dexamethasone in both dry eye and non-dry eye corneas (all P dry eye group. Compared with non-dry eye corneas, dry eye corneas have greater amounts of inflammation and neovascularization and also have a more robust response to anti-inflammatory and anti-angiogenic agents after ocular surface surgery. Trapping VEGF-A is effective in decreasing both angiogenesis and inflammation in dry eye corneas after ocular surface surgery.

  2. The effect of bevacizumab for anterior segment neovascularization after silicone oil removal in eyes with previous vitreoretinal surgery.

    Science.gov (United States)

    Batman, C; Ozdamar, Y

    2010-07-01

    To report the outcomes of the use of intracameral bevacizumab for iris neovascularization occurring after silicone oil (SO) removal in eyes undergoing vitreoretinal surgery (VRS). This study included 12 eyes that had iris neovascularization after SO removal. The clinical outcomes of 12 eyes after intravitreal bevacizumab injection were reviewed. There were eight men and four women with an average age of 41.58+/-12.68 years. All eyes had VRS for various vitreoretinal diseases. After the mean follow-up period of 9.7+/-5.3 months, SO removal was performed. Then, the patients were followed for more than 2 months and detailed retinal examinations and intraocular pressure (IOP) were normal during this period, but rubeosis iridis (RI) developed. RI was treated with 1 dose of 1.25 mg bevacizumab into the anterior chamber. After a mean follow-up period of 4.8+/-2.2 months, the regression of iris neovacularization was detected and IOP was below 21 mmHg in all eyes. Anterior segment neovascularization (ASNV) may develop through various mechanisms in patients with VRS after SO removal, and anterior chamber injection of bevacizumab may lead to regression of ASNV.

  3. Effectiveness of multiple therapeutic strategies in neovascular glaucoma patients: A PRISMA-compliant network meta-analysis.

    Science.gov (United States)

    Dong, Zixian; Gong, Jianyang; Liao, Rongfeng; Xu, Shaojun

    2018-04-01

    Neovascular glaucoma (NVG) is a severe secondary glaucoma with uncontrolled intraocular pressure that leads to serious eye pain and vision loss. Presently, the therapeutic strategies for NVG are diverse, but the therapeutic effects are still not ideal. We performed a network analysis to assess the effect of multiple therapeutic strategies on the treatment of NVG patients. We searched public electronic databases through April 2017 using the following keywords "neovascular glaucoma," "iris neovascularization," "hemorrhagic glaucoma," and "random" without language restrictions. The outcome considered in the present analysis was treatment success rate. A network meta-analysis and multilevel mixed-effects logistic regression were used to compare regimens. We included 27 articles assessing a total of 1884 NVG patients in our analysis. According to the network analysis, interferon and mitomycin plus trabeculectomy (94.9%), glaucoma valve implantation (86.9%), and iris photocoagulation plus trabeculectomy (81.9%) were the most likely to improve treatment success rate in NVG patients. The multilevel logistic regression analysis showed that glaucoma valve, bevacizumab, interferon, cyclophotocoagulation, trabeculectomy, iris photocoagulation, ranibizumab, and mitomycin had advantages in terms of improving treatment success rate in NVG patients. However, the application of retinal photocoagulation and vitrectomy reduced patient treatment success rate. The regimen including mitomycin, interferon, and trabeculectomy was the most likely to improve the treatment success rate in NVG patients. The application of glaucoma valve and bevacizumab were more beneficial for improving patient treatment success rate as a surgery and as an agent, respectively.

  4. Ranibizumab in the treatment of choroidal neovascularization on the border of an inferior staphyloma associated with tilted disc syndrome

    Directory of Open Access Journals (Sweden)

    Luis Arias

    2010-03-01

    Full Text Available Luis Arias1,2, Jordi Monés21Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona; 2Institut de la Màcula i de la Retina, Centro Médico Teknon, BarcelonaPurpose: To describe a case of choroidal neovascularization (CNV on the border of an inferior staphyloma associated with tilted disc syndrome treated with intravitreal ranibizumab.Patients: Observational case report.Methods: A patient with CNV on the border of an inferior staphyloma associated with tilted disc syndrome was imaged using fluorescein angiography, autofluorescence and spectral domain optical coherence tomography, and treated with intravitreal injections of ranibizumab. Results: The patient received 3 ranibizumab injections during the 9-month follow-up. The visual acuity improved from 20/40 to 20/32 and the foveal thickness reduced from 470 microns to 248 microns. The angiograms showed resolution of leakage associated with CNV. There were no adverse events.Conclusion: Intravitreal ranibizumab is an efficacious and safe treatment in the management of choroidal neovascularization on the border of an inferior staphyloma associated with tilted disc syndrome.Keywords: intravitreal ranibizumab, choroidal neovascularization, tilted disc syndrome, inferior staphyloma

  5. [Krypton laser photocoagulation at low power setting for age-related macular degeneration complicated with subfoveal choroidal neovascularization].

    Science.gov (United States)

    Zhang, Cheng-fen; Jia, Yan; Li, Zhi-qing; Du, Hong; Han, Bao-ling

    2004-12-01

    To evaluate the efficacy of krypton laser photocoagulation for treatment of age-related macular degeneration (AMD) complicated with mainly subfoveal classic choroidal neovascularization (CNV). Seventeen eyes of 17 cases, aged 50 - 74 years (averaged 60.8 years) with mainly subfoveal classic choroidal neovascularization were treated with krypton laser at lower power setting. The treatment was completed in one session. Another course of treatment was given 4 weeks later if there was active leakage demonstrated at the CNV area. Visual acuity, anterior segment and fundus examination, perimetry test, fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were performed before and after treatment. The follow-up period was 3.5 years on average (1 - 8 years). There was no immediately decrease of visual acuity after treatment. All treated eyes showed absorption of hemorrhages and/or exudates and diminished leakages. Visual acuity was stable in 8 eyes; improved in 6 eyes (>/= 2 lines), and decreased in 3 eyes (Krypton laser photocoagulation at low power setting is an effective treatment for AMD with mainly classic subfoveal choroidal neovascularization.

  6. Treatment of Non-neovascular Idiopathic Macular Telangiectasia Type 2 with Intravitreal Ranibizumab: Results of a Phase II Clinical Trial

    Science.gov (United States)

    Toy, Brian C.; Koo, Euna; Cukras, Catherine; Meyerle, Catherine B.; Chew, Emily Y.; Wong, Wai T.

    2015-01-01

    Purpose To evaluate the safety and preliminary efficacy of intravitreal ranibizumab for non-neovascular idiopathic macular telangiectasia, type 2 (IMT2). Methods Single-center, open-label phase II clinical trial enrolling 5 participants with bilateral non-neovascular IMT2. Intravitreal ranibizumab (0.5mg) was administered every 4 weeks in the study eye for 12 months with the contralateral eye observed. Outcome measures included changes in: best corrected visual acuity (BCVA), area of late-phase leakage on fluorescein angiography (FA), and retinal thickness on optical coherence tomography (OCT). Results The study treatment was well-tolerated and associated with few adverse events. Change in BCVA at 12 months was not significantly different between treated study eyes (0.0±7.5 letters) and control fellow eyes (+2.2±1.9 letters). However, decreases in the area of late-phase FA leakage (−33±20% for study eyes, +1±8% for fellow eyes) and in OCT central subfield retinal thickness (−11.7±7.0% for study eyes and −2.9±3.5% for fellow eyes) were greater in study eyes compared to fellow eyes. Conclusions Despite significant anatomical responses to treatment, functional improvement in visual acuity was not detected. Intravitreal ranibizumab administered monthly over a time course of 12 months is unlikely to provide a general and significant benefit to patients with non-neovascular IMT2. PMID:22266930

  7. Visual outcome of ranibizumab therapy for neovascular age related macular degeneration in the black population: a report of five cases

    Directory of Open Access Journals (Sweden)

    Roopa Vemala

    2010-08-01

    Full Text Available Roopa Vemala, Bhaskar Gupta, Sobha SivaprasadLaser and Retinal Research Unit, King’s College Hospital, London SE5 9RS, UKIntroduction: Neovascular age related macular degeneration (AMD is relatively uncommon in the black population. We report the 12-month outcome of ranibizumab therapy in five black patients with choroidal neovascular membrane (CNV secondary to AMD.Material and methods: Retrospective analysis of a prospective audit database maintained for all patients on ranibizumab therapy in a retinal specialist unit that caters to a multi-ethnic cohort in London, United Kingdom.Results: At 12 months, all the 5 patients maintained stable vision (loss of less than 15 ETDRS letters. However, none of them gained more than 15 ETDRS letters. All eyes showed early subretinal fibrosis while 2 patients showed extended areas of retinal pigment atrophy.Conclusion: Our case studies indicate that ranibizumab stabilizes the vision in black patients with CNV secondary to AMD but they tend to develop early subretinal fibrosis and retinal pigment atrophy.Keywords: choroidal neovascular membrane, Afro-Caribbean, blacks

  8. Increased levels of circulating CD34+ cells in neovascular age-related macular degeneration: relation with clinical and OCT features.

    Science.gov (United States)

    Kara, Caner; Özdal, Pınar Ç; Beyazyıldız, Emrullah; Özcan, Nurgül E; Teke, Mehmet Y; Vural, Gülden; Öztürk, Faruk

    2018-01-01

    To investigate the levels of circulating CD34+ stem cells in patients with neovascular type age-related macular degeneration (AMD) and its relation with clinical and optical coherence tomography (OCT) findings. The study consisted of 55 patients: 28 patients (18 male and 10 female) with neovascular type AMD as a study group and 27 patients (12 male and 15 female) scheduled for cataract surgery as a control group. The level of CD34+ stem cells was measured by flow cytometry. Demographic and clinical data were recorded. The mean ages of patients in the study and control groups were 71 ± 8 and 68 ± 6 years, respectively. There was no statistically significant difference in terms of age, sex, or systemic disease association between study and control groups. However, smoking status was significantly higher in the study group (67.9% vs 37.0%; p = 0.02). Stem cell levels were significantly higher in the study group (1.5 ± 0.9 vs 0.5 ± 0.3; p<0.001), but there was no relation between stem cell levels and clinical and OCT findings. Increased circulating CD34+ stem cell levels were observed in patients with choroidal neovascular membrane associated with AMD, but no significant relation was found between cell levels and clinical and OCT findings.

  9. Bevacizumab treatment reduces retinal neovascularization in a mouse model of retinopathy of prematurity

    Institute of Scientific and Technical Information of China (English)

    Fei; Feng; Yan; Cheng; Qing-Huai; Liu

    2014-01-01

    ·AIM: To evaluate the effect of different bevacizumab concentrations on retinal neovascularization in a retinopathy of prematurity(ROP) mouse model.·METHODS: A total of 60 of C57BL/6 J mice were exposed to 75% ±2% oxygen from postnatal d7 to postnatal d12. Fifteen nonexposed mice served as negative controls(group A). On d12, 30 mice(group C)were injected with 2.5 μg intravitreal bevacizumab(IVB),30 mice(group D) were injected with 1.25 μg IVB in one eye. The contralateral eyes were injected with balanced salt solution(BSS)(control group =group B). The adenosine diphosphatase(ADPase) histochemical technique was used for retinal flat mount to assess the oxygen-induced changes of retinal vessels.Neovascularization was quantified by counting the endothelial cell proliferation on the vitreal side of the inner limiting membrane of the retina. Histological changes were examined by light microscopy. The mRNA levels of vascular endothelial growth factor(VEGF) were quantified by Real-time PCR. Western-blotting analysis was performed to examine the expression of P-VEGFR.· RESULTS: Comparing with the control group B,regular distributions and reduced tortuosity of vessels were observed in our retinal flat mounts in groups C and D. The endothelial cell count per histological section was lower in groups C(P <0.0001) and D(P <0.0001) compared with the control group B. Histological evaluation showed no retinal toxicity in any group. In all oxygen treated groups VEGF mRNA expression was significantly increased as compared to age-matched controls. No significant change in VEGF mRNA expression could be achieved in either of the treatments or the oxygen controls. The results of the Western blot were consistent with that of the Real-time PCR analysis.·CONCLUSION: An intravitreal injection of bevacizumab is able to reduce angioproliferative retinopathy in a mouse model for oxygen-induced retinopathy.

  10. Decellularized matrix from tumorigenic human mesenchymal stem cells promotes neovascularization with galectin-1 dependent endothelial interaction.

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    Jorge S Burns

    Full Text Available BACKGROUND: Acquisition of a blood supply is fundamental for extensive tumor growth. We recently described vascular heterogeneity in tumours derived from cell clones of a human mesenchymal stem cell (hMSC strain (hMSC-TERT20 immortalized by retroviral vector mediated human telomerase (hTERT gene expression. Histological analysis showed that cells of the most vascularized tumorigenic clone, -BD11 had a pericyte-like alpha smooth muscle actin (ASMA+ and CD146+ positive phenotype. Upon serum withdrawal in culture, -BD11 cells formed cord-like structures mimicking capillary morphogenesis. In contrast, cells of the poorly tumorigenic clone, -BC8 did not stain for ASMA, tumours were less vascularized and serum withdrawal in culture led to cell death. By exploring the heterogeneity in hMSC-TERT20 clones we aimed to understand molecular mechanisms by which mesenchymal stem cells may promote neovascularization. METHODOLOGY/PRINCIPAL FINDINGS: Quantitative qRT-PCR analysis revealed similar mRNA levels for genes encoding the angiogenic cytokines VEGF and Angiopoietin-1 in both clones. However, clone-BD11 produced a denser extracellular matrix that supported stable ex vivo capillary morphogenesis of human endothelial cells and promoted in vivo neovascularization. Proteomic characterization of the -BD11 decellularized matrix identified 50 extracellular angiogenic proteins, including galectin-1. siRNA knock down of galectin-1 expression abrogated the ex vivo interaction between decellularized -BD11 matrix and endothelial cells. More stable shRNA knock down of galectin-1 expression did not prevent -BD11 tumorigenesis, but greatly reduced endothelial migration into -BD11 cell xenografts. CONCLUSIONS: Decellularized hMSC matrix had significant angiogenic potential with at least 50 angiogenic cell surface and extracellular proteins, implicated in attracting endothelial cells, their adhesion and activation to form tubular structures. hMSC -BD11 surface galectin-1

  11. Idiopathic polypoidal choroidal vasculopathy in Thai patients with clinical and angiographic choroidal neovascularization

    Directory of Open Access Journals (Sweden)

    Bhoomibunchoo C

    2017-02-01

    Full Text Available Chavakij Bhoomibunchoo,1 Yosanan Yospaiboon,1 Somanus Thoongsuwan,2 Duangnate Rojanaporn,3 Nawat Watanachai,4 Pichai Jirarattanasopa,5 Nattapon Wongcumchang,6 Atchara Amphornphruet,7 Sritatath Vongkulsiri,8 Eakkachai Arayangkoon9 1Department of Ophthalmology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 2Department of Ophthalmology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, 3Department of Ophthalmology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 4Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 5Department of Ophthalmology, Faculty of Medicine, Prince of Songkla University, Songkhla, 6Department of Ophthalmology, Faculty of Medicine, Thammasat University, Pathum Thani, 7Department of Ophthalmology, Rajavithi Hospital, Bangkok, 8Department of Ophthalmology, Phramongkutklao Hospital, Bangkok, 9Department of Ophthalmology, Mettapracharak Hospital, Nakhon Pathom, Thailand Objective: This study aimed to study the prevalence and characteristics of idiopathic polypoidal choroidal vasculopathy (IPCV in Thai patients with clinical and angiographic choroidal neovascularization (CNV.Patients and methods: A consecutive case study of 140 patients presenting with CNV was conducted in nine large referral eye centers throughout Thailand. The demographic data, fundus photographs, fundus fluorescein angiography and indocyanine green angiography of the patients were analyzed.Results: Of 129 patients with clinical and angiographic CNV, IPCV was diagnosed in 100 patients (77.52%, idiopathic CNVs in 16 patients (12.40% and age-related macular degeneration (AMD in 12 patients (9.30%. Of the 107 eyes with IPCV, 90 eyes (84.11% had both branching venous networks (BVNs and polypoidal lesions. Most IPCV patients (93% had unilateral involvement and were at a younger age than AMD patients. In all, 79 eyes (73.83% had lesions found in the macular area, 14 eyes (13.08% in the

  12. Lentivirus-mediated RNA interference of vascular endothelial growth factor in monkey eyes with iris neovascularization.

    Science.gov (United States)

    Yuan, Meng-Ke; Tao, Yong; Yu, Wen-Zhen; Kai, Wang; Jiang, Yan-Rong

    2010-08-25

    To explore the in vivo anti-angiogenesis effects resulting from lentivirus-mediated RNAi of vascular endothelial growth factor (VEGF) in monkeys with iris neovascularization (INV). Five specific recombinant lentiviral vectors for RNA interference, targeting Macaca mulatta VEGFA, were designed and the one with best knock down efficacy (LV-GFP-VEGFi1) in H1299 cells and RF/6A cells was selected by real-time PCR for in vivo use. A laser-induced retinal vein occlusion model was established in one eye of seven cynomolgus monkeys. In monkeys number 1, 3, and 5 (Group 1), the virus (1x10(8) particles) was intravitreally injected into the preretinal space of the animal's eye immediately after laser coagulation; and in monkeys number 2, 4, and 6 (Group 2), the virus (1x10(8) particles) was injected at 10 days after laser coagulation. In monkey number 7, a blank control injection was performed. In monkeys number 1 and 2, virus without RNAi sequence was used; in monkeys number 3 and 4, virus with nonspecific RNAi sequence was used; and in monkeys 5 and 6, LV-GFP-VEGFi1 was used. In monkey number 5, at 23 days after laser treatment, no obvious INV was observed, while fluorescein angiography of the iris revealed high fluorescence at the margin of pupil and point posterior synechiae. At 50 days after laser treatment, only a slight ectropion uvea was found. However, in the other eyes, obvious INV or hyphema was observed. The densities of new iridic vessels all significantly varied: between monkey number 5 and number 3 (36.01+/-4.49/mm(2) versus 48.68+/-9.30/mm(2), p=0.025), between monkey number 3 and monkey number 7 (48.68+/-9.30/mm(2) versus 74.38+/-9.23/mm(2), p=0.002), and between monkey number 5 and number 7 (36.01+/-4.49/mm(2) versus 74.38+/-9.23/mm(2), p<0.001). Lentivirus-mediated RNAi of VEGF may be a new strategy to treat iris neovascularization, while further studies are needed to investigate the long-term effect.

  13. Renal blood flow and oxygenation drive nephron progenitor differentiation.

    Science.gov (United States)

    Rymer, Christopher; Paredes, Jose; Halt, Kimmo; Schaefer, Caitlin; Wiersch, John; Zhang, Guangfeng; Potoka, Douglas; Vainio, Seppo; Gittes, George K; Bates, Carlton M; Sims-Lucas, Sunder

    2014-08-01

    During kidney development, the vasculature develops via both angiogenesis (branching from major vessels) and vasculogenesis (de novo vessel formation). The formation and perfusion of renal blood vessels are vastly understudied. In the present study, we investigated the regulatory role of renal blood flow and O2 concentration on nephron progenitor differentiation during ontogeny. To elucidate the presence of blood flow, ultrasound-guided intracardiac microinjection was performed, and FITC-tagged tomato lectin was perfused through the embryo. Kidneys were costained for the vasculature, ureteric epithelium, nephron progenitors, and nephron structures. We also analyzed nephron differentiation in normoxia compared with hypoxia. At embryonic day 13.5 (E13.5), the major vascular branches were perfused; however, smaller-caliber peripheral vessels remained unperfused. By E15.5, peripheral vessels started to be perfused as well as glomeruli. While the interior kidney vessels were perfused, the peripheral vessels (nephrogenic zone) remained unperfused. Directly adjacent and internal to the nephrogenic zone, we found differentiated nephron structures surrounded and infiltrated by perfused vessels. Furthermore, we determined that at low O2 concentration, little nephron progenitor differentiation was observed; at higher O2 concentrations, more differentiation of the nephron progenitors was induced. The formation of the developing renal vessels occurs before the onset of blood flow. Furthermore, renal blood flow and oxygenation are critical for nephron progenitor differentiation. Copyright © 2014 the American Physiological Society.

  14. THE TYPE IIb SUPERNOVA 2011dh FROM A SUPERGIANT PROGENITOR

    International Nuclear Information System (INIS)

    Bersten, Melina C.; Nomoto, Ken'ichi; Folatelli, Gastón; Maeda, Keiichi; Benvenuto, Omar G.; Ergon, Mattias; Sollerman, Jesper; Benetti, Stefano; Ochner, Paolo; Tomasella, Lina; Botticella, Maria Teresa; Fraser, Morgan; Kotak, Rubina

    2012-01-01

    A set of hydrodynamical models based on stellar evolutionary progenitors is used to study the nature of SN 2011dh. Our modeling suggests that a large progenitor star—with R ∼ 200 R ☉ —is needed to reproduce the early light curve (LC) of SN 2011dh. This is consistent with the suggestion that the yellow super-giant star detected at the location of the supernova (SN) in deep pre-explosion images is the progenitor star. From the main peak of the bolometric LC and expansion velocities, we constrain the mass of the ejecta to be ≈2 M ☉ , the explosion energy to be E = (6-10) × 10 50 erg, and the 56 Ni mass to be approximately 0.06 M ☉ . The progenitor star was composed of a helium core of 3-4 M ☉ and a thin hydrogen-rich envelope of ≈0.1M ☉ with a main-sequence mass estimated to be in the range of 12-15 M ☉ . Our models rule out progenitors with helium-core masses larger than 8 M ☉ , which correspond to M ZAMS ∼> 25M ☉ . This suggests that a single star evolutionary scenario for SN 2011dh is unlikely.

  15. NFIX Regulates Neural Progenitor Cell Differentiation During Hippocampal Morphogenesis

    Science.gov (United States)

    Heng, Yee Hsieh Evelyn; McLeay, Robert C.; Harvey, Tracey J.; Smith, Aaron G.; Barry, Guy; Cato, Kathleen; Plachez, Céline; Little, Erica; Mason, Sharon; Dixon, Chantelle; Gronostajski, Richard M.; Bailey, Timothy L.; Richards, Linda J.; Piper, Michael

    2014-01-01

    Neural progenitor cells have the ability to give rise to neurons and glia in the embryonic, postnatal and adult brain. During development, the program regulating whether these cells divide and self-renew or exit the cell cycle and differentiate is tightly controlled, and imbalances to the normal trajectory of this process can lead to severe functional consequences. However, our understanding of the molecular regulation of these fundamental events remains limited. Moreover, processes underpinning development of the postnatal neurogenic niches within the cortex remain poorly defined. Here, we demonstrate that Nuclear factor one X (NFIX) is expressed by neural progenitor cells within the embryonic hippocampus, and that progenitor cell differentiation is delayed within Nfix−/− mice. Moreover, we reveal that the morphology of the dentate gyrus in postnatal Nfix−/− mice is abnormal, with fewer subgranular zone neural progenitor cells being generated in the absence of this transcription factor. Mechanistically, we demonstrate that the progenitor cell maintenance factor Sry-related HMG box 9 (SOX9) is upregulated in the hippocampus of Nfix−/− mice and demonstrate that NFIX can repress Sox9 promoter-driven transcription. Collectively, our findings demonstrate that NFIX plays a central role in hippocampal morphogenesis, regulating the formation of neuronal and glial populations within this structure. PMID:23042739

  16. Strategies to reverse endothelial progenitor cell dysfunction in diabetes.

    Science.gov (United States)

    Petrelli, Alessandra; Di Fenza, Raffaele; Carvello, Michele; Gatti, Francesca; Secchi, Antonio; Fiorina, Paolo

    2012-01-01

    Bone-marrow-derived cells-mediated postnatal vasculogenesis has been reported as the main responsible for the regulation of vascular homeostasis in adults. Since their discovery, endothelial progenitor cells have been depicted as mediators of postnatal vasculogenesis for their peculiar phenotype (partially staminal and partially endothelial), their ability to differentiate in endothelial cell line and to be incorporated into the vessels wall during ischemia/damage. Diabetes mellitus, a condition characterized by cardiovascular disease, nephropathy, and micro- and macroangiopathy, showed a dysfunction of endothelial progenitor cells. Herein, we review the mechanisms involved in diabetes-related dysfunction of endothelial progenitor cells, highlighting how hyperglycemia affects the different steps of endothelial progenitor cells lifetime (i.e., bone marrow mobilization, trafficking into the bloodstream, differentiation in endothelial cells, and homing in damaged tissues/organs). Finally, we review preclinical and clinical strategies that aim to revert diabetes-induced dysfunction of endothelial progenitor cells as a means of finding new strategies to prevent diabetic complications.

  17. Strategies to Reverse Endothelial Progenitor Cell Dysfunction in Diabetes

    Directory of Open Access Journals (Sweden)

    Alessandra Petrelli

    2012-01-01

    Full Text Available Bone-marrow-derived cells-mediated postnatal vasculogenesis has been reported as the main responsible for the regulation of vascular homeostasis in adults. Since their discovery, endothelial progenitor cells have been depicted as mediators of postnatal vasculogenesis for their peculiar phenotype (partially staminal and partially endothelial, their ability to differentiate in endothelial cell line and to be incorporated into the vessels wall during ischemia/damage. Diabetes mellitus, a condition characterized by cardiovascular disease, nephropathy, and micro- and macroangiopathy, showed a dysfunction of endothelial progenitor cells. Herein, we review the mechanisms involved in diabetes-related dysfunction of endothelial progenitor cells, highlighting how hyperglycemia affects the different steps of endothelial progenitor cells lifetime (i.e., bone marrow mobilization, trafficking into the bloodstream, differentiation in endothelial cells, and homing in damaged tissues/organs. Finally, we review preclinical and clinical strategies that aim to revert diabetes-induced dysfunction of endothelial progenitor cells as a means of finding new strategies to prevent diabetic complications.

  18. Human retinal pigment epithelial cell-induced apoptosis in activated T cells

    DEFF Research Database (Denmark)

    Jørgensen, A; Wiencke, A K; la Cour, M

    1998-01-01

    human retinal pigment epithelial (RPE) cells can induce apoptosis in activated T cells. METHODS: Fas ligand (FasL) expression was detected by flow cytometry and immunohistochemistry. Cultured RPE cells were cocultured with T-cell lines and peripheral blood lymphocytes for 6 hours to 2 days. Induction...... of apoptosis was detected by 7-amino-actinomycin D and annexin V staining. RESULTS: Retinal pigment epithelial cells expressed FasL and induced apoptosis in activated Fas+ T cells. Blocking of Fas-FasL interaction with antibody strongly inhibited RPE-mediated T-cell apoptosis. Retinal pigment epithelial cells...... induced apoptosis in several activated T-cell populations and T-cell lines, including T-cell antigen receptor (TCR)-CD3-negative T-cell lines. In contrast, RPE cells induced little or no apoptosis in resting peripheral T cells. Major histocompatibility complex (MHC) class II monoclonal antibodies, which...

  19. Hyperglycemia and oxidized-LDL exert a deleterious effect on endothelial progenitor cell migration in type 2 diabetes mellitus.

    Science.gov (United States)

    Hamed, Saher; Brenner, Benjamin; Abassi, Zaid; Aharon, Anat; Daoud, Deeb; Roguin, Ariel

    2010-09-01

    Type 2 diabetes mellitus (DM) patients with coronary artery disease (CAD) have elevated plasma oxidized-LDL (OxLDL) levels and impaired neovascularization. Hyperglycemia and hyperlipidemia impair endothelial progenitor cell (EPC) migration, and endothelial nitric oxide (NO) bioavailability and NO synthase (NOS) activity are essential for EPC migration. Stromal-derived factor-1alpha (SDF1alpha) contributes to EPC mobilization and homing by stimulating the CXC receptor-4 (CXCR4) on the EPC plasmalemma to activate the Pi3K/Akt/eNOS signaling pathway. Therefore, we investigated the effect of high glucose (HG) and OxLDL on the migration and NO bioavailability of EPCs from healthy individuals, and then correlated the findings with those of EPCs from type 2 DM patients with and without CAD. EPCs from 15 healthy and 55 patients were exposed to HG, OxLDL, or both before evaluating EPC count, migration and NO production, and expression of CXCR4 and members of Pi3K/Akt/eNOS signaling cascade. Counts, migration, CXCR4 expression, and NO production were significantly reduced in EPCs from DM and CAD patients compared with that obtained in EPCs from healthy, and were further reduced in DM patients with CAD. The expression of CXCR4 and activation of Pi3K/Akt/eNOS signaling cascade were suppressed in OxLDL- and HG-treated EPCs, and this suppression was exacerbated when EPCs were treated simultaneously with HG and OxLDL. Hyperglycemia and elevated circulating OxLDL in DM patients with CAD severely impair EPC migration. These results suggest that the underlying mechanism for this impaired EPC migration is linked to the CXCR4/Pi3K/Akt/eNOS signaling pathway. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  20. Production and Functional Characterization of Murine Osteoclasts Differentiated from ER-Hoxb8-Immortalized Myeloid Progenitor Cells.

    Directory of Open Access Journals (Sweden)

    Frank Zach

    Full Text Available In vitro differentiation into functional osteoclasts is routinely achieved by incubation of embryonic stem cells, induced pluripotent stem cells, or primary as well as cryopreserved spleen and bone marrow-derived cells with soluble receptor activator of nuclear factor kappa-B ligand and macrophage colony-stimulating factor. Additionally, osteoclasts can be derived from co-cultures with osteoblasts or by direct administration of soluble receptor activator of nuclear factor kappa-B ligand to RAW 264.7 macrophage lineage cells. However, despite their benefits for osteoclast-associated research, these different methods have several drawbacks with respect to differentiation yields, time and animal consumption, storage life of progenitor cells or the limited potential for genetic manipulation of osteoclast precursors. In the present study, we therefore established a novel protocol for the differentiation of osteoclasts from murine ER-Hoxb8-immortalized myeloid stem cells. We isolated and immortalized bone marrow cells from wild type and genetically manipulated mouse lines, optimized protocols for osteoclast differentiation and compared these cells to osteoclasts derived from conventional sources. In vitro generated ER-Hoxb8 osteoclasts displayed typical osteoclast characteristics such as multi-nucleation, tartrate-resistant acid phosphatase staining of supernatants and cells, F-actin ring formation and bone resorption activity. Furthermore, the osteoclast differentiation time course was traced on a gene expression level. Increased expression of osteoclast-specific genes and decreased expression of stem cell marker genes during differentiation of osteoclasts from ER-Hoxb8-immortalized myeloid progenitor cells were detected by gene array and confirmed by semi-quantitative and quantitative RT-PCR approaches. In summary, we established a novel method for the quantitative production of murine bona fide osteoclasts from ER-Hoxb8 stem cells generated from

  1. Development and molecular composition of the hepatic progenitor cell niche.

    Science.gov (United States)

    Vestentoft, Peter Siig

    2013-05-01

    End-stage liver diseases represent major health problems that are currently treated by liver transplantation. However, given the world-wide shortage of donor livers novel strategies are needed for therapeutic treatment. Adult stem cells have the ability to self-renew and differentiate into the more specialized cell types of a given organ and are found in tissues throughout the body. These cells, whose progeny are termed progenitor cells in human liver and oval cells in rodents, have the potential to treat patients through the generation of hepatic parenchymal cells, even from the patient's own tissue. Little is known regarding the nature of the hepatic progenitor cells. Though they are suggested to reside in the most distal part of the biliary tree, the canal of Hering, the lack of unique surface markers for these cells has hindered their isolation and characterization. Upon activation, they proliferate and form ductular structures, termed "ductular reactions", which radiate into the hepatic parenchyma. The ductular reactions contain activated progenitor cells that not only acquire a phenotype resembling that observed in developing liver but also display markers of differentiation shared with the cholangiocytic or hepatocytic lineages, the two parenchymal hepatic cell types. Interactions between the putative progenitor cells, the surrounding support cells and the extracellular matrix scaffold, all constituting the progenitor cell niche, are likely to be important for regulating progenitor cell activity and differentiation. Therefore, identifying novel progenitor cell markers and deciphering their microenvironment could facilitate clinical use. The aims of the present PhD thesis were to expand knowledge of the hepatic progenitor cell niche and characterize it both during development and in disease. Several animal models of hepatic injury are known to induce activation of the progenitor cells. In order to identify possible progenitor cell markers and niche components

  2. Relationship between Plaque Echo, Thickness and Neovascularization Assessed by Quantitative and Semi-quantitative Contrast-Enhanced Ultrasonography in Different Stenosis Groups.

    Science.gov (United States)

    Song, Yan; Feng, Jun; Dang, Ying; Zhao, Chao; Zheng, Jie; Ruan, Litao

    2017-12-01

    The aim of this study was to determine the relationship between plaque echo, thickness and neovascularization in different stenosis groups using quantitative and semi-quantitative contrast-enhanced ultrasound (CEUS) in patients with carotid atherosclerosis plaque. A total of 224 plaques were divided into mild stenosis (Quantitative and semi-quantitative methods were used to assess plaque neovascularization and determine the relationship between plaque echo, thickness and neovascularization. Correlation analysis revealed no relationship of neovascularization with plaque echo in the groups using either quantitative or semi-quantitative methods. Furthermore, there was no correlation of neovascularization with plaque thickness using the semi-quantitative method. The ratio of areas under the curve (RAUC) was negatively correlated with plaque thickness (r = -0.317, p = 0.001) in the mild stenosis group. With the quartile method, plaque thickness of the mild stenosis group was divided into four groups, with significant differences between the 1.5-2.2 mm and ≥3.5 mm groups (p = 0.002), 2.3-2.8 mm and ≥3.5 mm groups (p quantitative and quantitative CEUS methods characterizing neovascularization of plaque are equivalent with respect to assessing relationships between neovascularization, echogenicity and thickness. However, the quantitative method could fail for plaque <3.5 mm because of motion artifacts. Copyright © 2017 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

  3. Omega 3 fatty acids reduce myeloid progenitor cell frequency in the bone marrow of mice and promote progenitor cell differentiation

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    Sollars Vincent E

    2009-03-01

    Full Text Available Abstract Background Omega 3 fatty acids have been found to inhibit proliferation, induce apoptosis, and promote differentiation in various cell types. The processes of cell survival, expansion, and differentiation are of key importance in the regulation of hematopoiesis. We investigated the role of omega 3 fatty acids in controlling the frequency of various myeloid progenitor cells in the bone marrow of mice. Increased progenitor cell frequency and blocked differentiation are characteristics of hematopoietic disorders of the myeloid lineage, such as myeloproliferative diseases and myeloid leukemias. Results We found that increasing the proportion of omega 3 fatty acids relative to the proportion of omega 6 fatty acids in the diet caused increased differentiation and reduced the frequency of myeloid progenitor cells in the bone marrow of mice. Furthermore, this had no adverse effect on peripheral white blood cell counts. Conclusion Our results indicate that omega 3 fatty acids impact hematopoietic differentiation by reducing myeloid progenitor cell frequency in the bone marrow and promoting progenitor cell differentiation. Further exploration of this discovery could lead to the use of omega 3 fatty acids as a therapeutic option for patients that have various disorders of hematopoiesis.

  4. Establishment of bipotent progenitor cell clone from rat skeletal muscle.

    Science.gov (United States)

    Murakami, Yousuke; Yada, Erica; Nakano, Shin-ichi; Miyagoe-Suzuki, Yuko; Hosoyama, Tohru; Matsuwaki, Takashi; Yamanouchi, Keitaro; Nishihara, Masugi

    2011-12-01

    The present study describes the isolation, cloning and characterization of adipogenic progenitor cells from rat skeletal muscle. Among the obtained 10 clones, the most highly adipogenic progenitor, 2G11 cells, were further characterized. In addition to their adipogenicity, 2G11 cells retain myogenic potential as revealed by formation of multinucleated myotubes when co-cultured with myoblasts. 2G11 cells were resistant to an inhibitory effect of basic fibroblast growth factor on adipogenesis, while adipogenesis of widely used preadipogenic cell line, 3T3-L1 cells, was suppressed almost completely by the same treatment. In vivo transplantation experiments revealed that 2G11 cells are able to possess both adipogenicity and myogenicity in vivo. These results indicate the presence of bipotent progenitor cells in rat skeletal muscle, and suggest that such cells may contribute to ectopic fat formation in skeletal muscle. © 2011 The Authors. Animal Science Journal © 2011 Japanese Society of Animal Science.

  5. Rates and progenitors of type Ia supernovae

    Energy Technology Data Exchange (ETDEWEB)

    Wood-Vasey, William Michael [Univ. of California, Berkeley, CA (United States)

    2004-01-01

    analyzing the true sensitivity of a multi-epoch supernova search and finds a Type Ia supernova rate from z ~ 0.01-0.1 of rV = 4.26$+1.39 +0.10\\atop{-1.93 -0.10}$h3 x 10-4 SNe Ia/yr/Mpc3 from a preliminary analysis of a subsample of the SNfactory prototype search. Several unusual supernovae were found in the course of the SNfactory prototype search. One in particular, SN 2002ic, was the first SN Ia to exhibit convincing evidence for a circumstellar medium and offers valuable insight into the progenitors of Type Ia supernovae.

  6. Rates and progenitors of type Ia supernovae

    International Nuclear Information System (INIS)

    Wood-Vasey, William Michael

    2004-01-01

    analyzing the true sensitivity of a multi-epoch supernova search and finds a Type Ia supernova rate from z ∼ 0.01-0.1 of r V = 4.26 -1.93 -0.10 +1.39 +0.10 h 3 x 10 -4 SNe Ia/yr/Mpc 3 from a preliminary analysis of a subsample of the SNfactory prototype search. Several unusual supernovae were found in the course of the SNfactory prototype search. One in particular, SN 2002ic, was the first SN Ia to exhibit convincing evidence for a circumstellar medium and offers valuable insight into the progenitors of Type Ia supernovae

  7. Obstructive sleep apnea and endothelial progenitor cells

    Directory of Open Access Journals (Sweden)

    Wang Q

    2013-10-01

    Full Text Available Qing Wang,1,* Qi Wu,2,* Jing Feng,3,4 Xin Sun5 1The Second Respiratory Department of the First People's Hospital of Kunming, Yunnan, People's Republic of China; 2Tianjin Haihe Hospital, Tianjin, People's Republic of China; 3Respiratory Department of Tianjin Medical University General Hospital, Tianjin, People's Republic of China; 4Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, NC, USA; 5Respiratory Department of Tianjin Haihe Hospital, Tianjin, People's Republic of China *These authors contributed equally to this work Background: Obstructive sleep apnea (OSA occurs in 4% of middle-aged men and 2% of middle-aged women in the general population, and the prevalence is even higher in specific patient groups. OSA is an independent risk factor for a variety of cardiovascular diseases. Endothelial injury could be the pivotal determinant in the development of cardiovascular pathology in OSA. Endothelial damage ultimately represents a dynamic balance between the magnitude of injury and the capacity for repair. Bone marrow–derived endothelial progenitor cells (EPCs within adult peripheral blood present a possible means of vascular maintenance that could home to sites of injury and restore endothelial integrity and normal function. Methods: We summarized pathogenetic mechanisms of OSA and searched for available studies on numbers and functions of EPCs in patients with OSA to explore the potential links between the numbers and functions of EPCs and OSA. In particular, we tried to elucidate the molecular mechanisms of the effects of OSA on EPCs. Conclusion: Intermittent hypoxia cycles and sleep fragmentation are major pathophysiologic characters of OSA. Intermittent hypoxia acts as a trigger of oxidative stress, systemic inflammation, and sympathetic activation. Sleep fragmentation is associated with a burst of sympathetic activation and systemic inflammation. In most studies, a reduction in circulating EPCs has

  8. Antiangiogenic immunotherapy targeting Flk-1, DNA vaccine and adoptive T cell transfer, inhibits ocular neovascularization

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Han [Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582 (Japan); Sonoda, Koh-Hei, E-mail: sonodak@med.kyushu-u.ac.jp [Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582 (Japan); Hijioka, Kuniaki; Qiao, Hong; Oshima, Yuji; Ishibashi, Tatsuro [Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582 (Japan)

    2009-04-17

    Ocular neovascularization (NV) is the primary cause of blindness in a wide range of ocular diseases. The exact mechanism underlying the pathogenesis of ocular NV is not yet well understood, and so there is no satisfactory therapy for ocular NV. Here, we describe a strategy targeting Flk-1, a self-antigen overexpressed on proliferating endothelial cells in ocular NV, by antiangiogenic immunotherapy-DNA vaccine and adoptive T cell therapy. An oral DNA vaccine encoding Flk-1 carried by attenuated Salmonella typhimurium markedly suppressed development of laser-induced choroidal NV. We further demonstrated that adoptive transfer of vaccine-induced CD8{sup +} T cells reduced pathological preretinal NV, with a concomitant facilitation of physiological revascularization after oxygen-induced retinal vessel obliteration. However, physiological retinal vascular development was unaffected in neonatal mice transferred with vaccine-induced CD8{sup +} T cells. These findings suggested that antiangiogenic immunotherapy targeting Flk-1 such as vaccination and adoptive immunotherapy may contribute to future therapies for ocular NV.

  9. HTRA1 variant confers similar risks to geographic atrophy and neovascular age-related macular degeneration.

    Science.gov (United States)

    Cameron, D Joshua; Yang, Zhenglin; Gibbs, Daniel; Chen, Haoyu; Kaminoh, Yuuki; Jorgensen, Adam; Zeng, Jiexi; Luo, Ling; Brinton, Eric; Brinton, Gregory; Brand, John M; Bernstein, Paul S; Zabriskie, Norman A; Tang, Shibo; Constantine, Ryan; Tong, Zongzhong; Zhang, Kang

    2007-05-02

    Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the developed world. The two forms of advanced AMD, geographic atrophy (GA) and choroidal neovascularization (wet AMD), represent two types of degenerative processes in the macula that lead to loss of central vision. Soft confluent drusen, characterized by deposits in macula without visual loss are considered a precursor of advanced AMD. A single nucleotide polymorphism, rs11200638, in the promoter of HTRA1 has been shown to increases the risk for wet AMD. However, its impact on soft confluent drusen and GA or the relationship between them is unclear. To better understand the role the HTRA1 polymorphism plays in AMD subtypes, we genotyped an expanded Utah population with 658 patients having advanced AMD or soft confluent drusen and 294 normal controls and found that the rs11200638 was significantly associated with GA. This association remains significant conditional on LOC387715 rs10490924. In addition, rs11200638 was significantly associated with soft confluent drusen, which are strongly immunolabeled with HTRA1 antibody in an AMD eye with GA similar to wet AMD. Two-locus analyses were performed for CFH Y402H variant at 1q31 and the HTRA1 polymorphism. Together CFH and HTRA1 risk variants increase the odds of having AMD by more than 40 times. These findings expand the role of HTRA1 in AMD. Understanding the underlying molecular mechanism will provide an important insight in pathogenesis of AMD.

  10. [Neovascular form of age-related macular degeneration --current management in Poland and in Europe].

    Science.gov (United States)

    Teper, Sławomir; Nowińska, Anna; Lyssek-Boroń, Anita; Wylegała, Edward

    2014-07-01

    Currently in Poland neovascular form of age-related macular degeneration (AMD) is treated with vascular endothelial growth factor (VEGF) inhibitors--ranibizumab, aflibercept and bevacizumab. Photodynamic therapy is still refunded, although it is very rarely used. It can be estimated that only small minority (about 5-10%) of cases are properly treated due to mainly refunding restrictions in Poland. In countries with wider access to treatment 50% reduction in AMD-related blindness incidence was noted. Low-cost off-label anti-VEGF agent bevacizumab is almost inaccessible in Polish public health system because of law regulations. In order to increase availability of anti-VEGF injections vials of all mentioned drugs are divided which raises safety concerns. Despite new potent drug in the market aflibercept, cost of treatment remains very high. The optimal treatment regimen includes three monthly injections, after which is usually used pro re nata therapy based primarily on the outcome of macular optical coherence tomography. Routinely recommended antibiotic prophylaxis of injection-related endophthalmitis probably has no meaning apart from the generation of resistance.

  11. Mobile Laser Indirect Ophthalmoscope: For the Induction of Choroidal Neovascularization in a Mouse Model.

    Science.gov (United States)

    Weinberger, Dov; Bor-Shavit, Elite; Barliya, Tilda; Dahbash, Mor; Kinrot, Opher; Gaton, Dan D; Nisgav, Yael; Livnat, Tami

    2017-11-01

    This study aims to evaluate and standardize the reliability of a mobile laser indirect ophthalmoscope in the induction of choroidal neovascularization (CNV) in a mouse model. A diode laser indirect ophthalmoscope was used to induce CNV in pigmented male C57BL/6J mice. Standardization of spot size and laser intensity was determined using different aspheric lenses with increasing laser intensities applied around the optic disc. Development of CNV was evaluated 1, 5, and 14 days post laser application using fluorescein angiography (FA), histology, and choroidal flat mounts stained for the endothelial marker CD31 and FITC-dextran. Correlation between the number of laser hits to the number and size of developed CNV lesions was determined using flat mount choroid staining. The ability of intravitreally injected anti-human and anti-mouse VEGF antibodies to inhibit CNV induced by the mobile laser was evaluated. Laser parameters were standardized on 350 mW for 100 msec, using the 90 diopter lens to accomplish the highest incidence of Bruch's membrane rupture. CNV lesions' formation was validated on days 5 and 14 post laser injury, though FA showed leakage on as early as day 1. The number of laser hits was significantly correlated with the CNV area. CNV growth was successfully inhibited by both anti-human and mouse VEGF antibodies. The mobile laser indirect ophthalmoscope can serve as a feasible and a reliable alternative method for the CNV induction in a mouse model.

  12. Quantitative evaluation and modeling of two-dimensional neovascular network complexity: the surface fractal dimension

    International Nuclear Information System (INIS)

    Grizzi, Fabio; Russo, Carlo; Colombo, Piergiuseppe; Franceschini, Barbara; Frezza, Eldo E; Cobos, Everardo; Chiriva-Internati, Maurizio

    2005-01-01

    Modeling the complex development and growth of tumor angiogenesis using mathematics and biological data is a burgeoning area of cancer research. Architectural complexity is the main feature of every anatomical system, including organs, tissues, cells and sub-cellular entities. The vascular system is a complex network whose geometrical characteristics cannot be properly defined using the principles of Euclidean geometry, which is only capable of interpreting regular and smooth objects that are almost impossible to find in Nature. However, fractal geometry is a more powerful means of quantifying the spatial complexity of real objects. This paper introduces the surface fractal dimension (D s ) as a numerical index of the two-dimensional (2-D) geometrical complexity of tumor vascular networks, and their behavior during computer-simulated changes in vessel density and distribution. We show that D s significantly depends on the number of vessels and their pattern of distribution. This demonstrates that the quantitative evaluation of the 2-D geometrical complexity of tumor vascular systems can be useful not only to measure its complex architecture, but also to model its development and growth. Studying the fractal properties of neovascularity induces reflections upon the real significance of the complex form of branched anatomical structures, in an attempt to define more appropriate methods of describing them quantitatively. This knowledge can be used to predict the aggressiveness of malignant tumors and design compounds that can halt the process of angiogenesis and influence tumor growth

  13. Time-dependent LXR/RXR pathway modulation characterizes capillary remodeling in inflammatory corneal neovascularization.

    Science.gov (United States)

    Mukwaya, Anthony; Lennikov, Anton; Xeroudaki, Maria; Mirabelli, Pierfrancesco; Lachota, Mieszko; Jensen, Lasse; Peebo, Beatrice; Lagali, Neil

    2018-05-01

    Inflammation in the normally immune-privileged cornea can initiate a pathologic angiogenic response causing vision-threatening corneal neovascularization. Inflammatory pathways, however, are numerous, complex and are activated in a time-dependent manner. Effective resolution of inflammation and associated angiogenesis in the cornea requires knowledge of these pathways and their time dependence, which has, to date, remained largely unexplored. Here, using a model of endogenous resolution of inflammation-induced corneal angiogenesis, we investigate the time dependence of inflammatory genes in effecting capillary regression and the return of corneal transparency. Endogenous capillary regression was characterized by a progressive thinning and remodeling of angiogenic capillaries and inflammatory cell retreat in vivo in the rat cornea. By whole-genome longitudinal microarray analysis, early suppression of VEGF ligand-receptor signaling and inflammatory pathways preceded an unexpected later-phase preferential activation of LXR/RXR, PPARα/RXRα and STAT3 canonical pathways, with a concurrent attenuation of LPS/IL-1 inhibition of RXR function and Wnt/β-catenin signaling pathways. Potent downstream inflammatory cytokines such as Cxcl5, IL-1β, IL-6 and Ccl2 were concomitantly downregulated during the remodeling phase. Upstream regulators of the inflammatory pathways included Socs3, Sparc and ApoE. A complex and coordinated time-dependent interplay between pro- and anti-inflammatory signaling pathways highlights a potential anti-inflammatory role of LXR/RXR, PPARα/RXRα and STAT3 signaling pathways in resolving inflammatory corneal angiogenesis.

  14. Efficacy of intravitreal Ranibizumab injection for choroidal neovascularization secondary to pathologic myopia

    Directory of Open Access Journals (Sweden)

    Li-Hong Cui

    2016-03-01

    Full Text Available AIM:To observe the efficacy and safety of intravitreal Ranibizumab injection in patiens with choroidal neovascularization(CNVsecondary to pathologic myopia.METHODS:In this retrospective and comparative study,24 patients(25 eyeswith CNV secondary to pathologic myopia were enrolled. All patients were assessed by examinations of ETDRS visual acuity chart, preplaced-mirror ophthalmoscopy, fundus fluorescein angiography(FFA, indocyanine green angiography(ICGAand optical coherence tomography(OCT. Patiens received intravitreally injected ranibizumab 0.5mg(0.05mL. Treatments were repeated if the follow-up indicated that it was necessary. The follow-up periods were 4~10mo. Best corrected visual acuity(BCVA, central macular thickness(CMTand leakage of CNV before and after the treatment were compared. RESULTS:No local or systemic complications occurred in any patients during the treatment or follow-up. The average time of injection was 1.52. The mean BCVA was 23.93±12.46 letters before the therapy. In the last follow-up, the mean BCVA was 40.63±7.25 letters, improved by 14.27±9.36 letters and the difference was statically significant(t=5.74, Pt=3.96, PCONCLUSION:Intravitreal ranibizumab injection for CNV secondary to pathologic myopia is safe and effective, and this treatment can improve visual acuity, reduce retina edema and leakage of CNV.

  15. Topical Use of Angiopoietin-like Protein 2 RNAi-loaded Lipid Nanoparticles Suppresses Corneal Neovascularization

    Directory of Open Access Journals (Sweden)

    Yukako Taketani

    2016-01-01

    Full Text Available Corneal neovascularization (CNV is a sight-threatening condition that is encountered in various inflammatory settings including chemical injury. We recently confirmed that angiopoietin-like protein 2 (ANGPTL2 is a potent angiogenic and proinflammatory factor in the cornea, and we have produced a single-stranded proline-modified short hairpin anti-ANGPTL2 RNA interference molecule that is carried in a lipid nanoparticle (ANGPTL2 Li-pshRNA for topical application. In this study, we have further examined the topical delivery and anti-ANGPTL2 activity of this molecule and have found that fluorescence-labeled ANGPTL2 Li-pshRNA eye drops can penetrate all layers of the cornea and that ANGPTL2 mRNA expression was dramatically inhibited in both epithelium and stroma at 12 and 24 hours after administration. We also examined the inhibitory effect of ANGPTL2 Li-pshRNA on CNV in a mouse chemical injury model and found that the area of angiogenesis was significantly decreased in corneas treated with ANGPTL2 Li-pshRNA eye drops compared to controls. Together, these findings indicate that this modified RNA interference agent is clinically viable in a topical formulation for use against CNV.

  16. Association of Neovascular Glaucoma with Risk of Stroke: A Population-Based Cohort Study

    Directory of Open Access Journals (Sweden)

    Cheng-Wen Su

    2017-01-01

    Full Text Available Neovascular glaucoma (NVG, caused by ocular ischemia, is a serious ocular disease complicated by intractably increased intraocular pressure. Cerebrovascular accidents are classified into ischemic and hemorrhagic stroke. Based on the similar pathogenic mechanisms of NVG and ischemic stroke, we investigated the relationship between NVG and stroke by using a nationally representative sample. This study included 416 NVG patients and 4160 controls. Medical comorbidities were also evaluated. The cumulative incidence of ischemic stroke was 15.6% higher in the NVG cohort than in the control cohort (p<0.001; the incidence density rates of stroke were 3.80 and 1.19 per 10,000 person-years in the NVG and control cohorts, respectively. According to the multivariable Cox regression results, the estimated adjusted hazard ratio (aHR of stroke was 2.07 (95% confidence interval (CI = 1.41–3.02 for the NVG cohort. Furthermore, the NVG cohort was 2.24-fold more likely to develop ischemic stroke (95% CI = 1.51–3.32. The risk of ischemic stroke was higher in patients with hypertension (aHR = 2.09, 95% CI = 1.55–2.82 and in patients with diabetic retinopathy (aHR = 1.69, 95% CI = 1.05–2.72. Notably, patients with NVG have a higher risk of ischemic stroke, but not hemorrhagic stroke.

  17. Cerebrovascular accidents in patients treated for choroidal neovascularization with ranibizumab in randomized controlled trials.

    Science.gov (United States)

    Bressler, Neil M; Boyer, David S; Williams, David F; Butler, Steven; Francom, Steven F; Brown, Benton; Di Nucci, Flavia; Cramm, Timothy; Tuomi, Lisa L; Ianchulev, Tsontcho; Rubio, Roman G

    2012-10-01

    To analyze cerebrovascular accidents (CVAs) pooled from large, randomized, controlled clinical trials of ranibizumab treatment for neovascular age-related macular degeneration. Events in five trials (FOCUS, MARINA, ANCHOR, PIER, and SAILOR) were analyzed using a standard safety monitoring process. Exact methods, stratified by study, were used to test for treatment differences based on odds ratios. A stepwise logistic regression model was fit to classify subjects' risk for CVA based on medical history. Treatment differences in CVA rates at 1 year or 2 years were evaluated within risk groups using stratified exact methods. Pooled 2-year CVA rates were <3%; odds ratios (95% confidence intervals) for CVA risk were 1.2 (0.4-4.4) for ranibizumab 0.3-mg versus control, 2.2 (0.8-7.1) for 0.5 mg versus control, and 1.5 (0.8-3.0) for 0.5-mg versus 0.3-mg ranibizumab. No substantial increased risk of CVA for 0.5 mg versus 0.3 mg was identified in pooled analyses or any of the individual trials. In pooled analyses, the difference between 0.5-mg ranibizumab and control was larger (7.7 [1.2-177]) among high-risk CVA patients. This analysis provided some evidence, although not definitive, of a potential increased risk of CVA with ranibizumab versus control or with 0.5-mg versus 0.3-mg ranibizumab. Continued monitoring for CVA within clinical trials seems warrented.

  18. Antiangiogenic immunotherapy targeting Flk-1, DNA vaccine and adoptive T cell transfer, inhibits ocular neovascularization

    International Nuclear Information System (INIS)

    Zhang, Han; Sonoda, Koh-Hei; Hijioka, Kuniaki; Qiao, Hong; Oshima, Yuji; Ishibashi, Tatsuro

    2009-01-01

    Ocular neovascularization (NV) is the primary cause of blindness in a wide range of ocular diseases. The exact mechanism underlying the pathogenesis of ocular NV is not yet well understood, and so there is no satisfactory therapy for ocular NV. Here, we describe a strategy targeting Flk-1, a self-antigen overexpressed on proliferating endothelial cells in ocular NV, by antiangiogenic immunotherapy-DNA vaccine and adoptive T cell therapy. An oral DNA vaccine encoding Flk-1 carried by attenuated Salmonella typhimurium markedly suppressed development of laser-induced choroidal NV. We further demonstrated that adoptive transfer of vaccine-induced CD8 + T cells reduced pathological preretinal NV, with a concomitant facilitation of physiological revascularization after oxygen-induced retinal vessel obliteration. However, physiological retinal vascular development was unaffected in neonatal mice transferred with vaccine-induced CD8 + T cells. These findings suggested that antiangiogenic immunotherapy targeting Flk-1 such as vaccination and adoptive immunotherapy may contribute to future therapies for ocular NV.

  19. Bevacizumab (Avastin and Thermal Laser Combination Therapy for Peripapillary Choroidal Neovascular Membranes

    Directory of Open Access Journals (Sweden)

    Sean D. Adrean

    2017-01-01

    Full Text Available Objective. This is a retrospective interventional case series describing the results of 5 eyes from 5 patients with symptomatic peripapillary choroidal neovascularization (CNVM receiving initial bevacizumab treatment followed by thermal laser and bevacizumab combination therapy. Methods. Patients received intravitreal bevacizumab injections until the lesions were well-defined. Thermal laser ablation was then administered and followed by an additional bevacizumab injection after one week. Visual outcomes, OCT changes, and rates of recurrence were recorded and analyzed. Results. Median visual outcomes improved from 20/50 to 20/30 (p=0.0232. Median central macular thickness decreased from 347 μm to 152 μm (p=0.0253. The mean visual improvement was 3 lines. An average of 3.8 bevacizumab injections per patient were given overall. Patients were followed for an average of 24 months, during which all eyes were absent for recurrence. Conclusion. Symptomatic peripapillary CNVM may be successfully managed with bevacizumab followed by a combination of thermal laser and bevacizumab without the need for frequent retreatment. The area requiring treatment may be better defined using bevacizumab, limiting the ablation of the healthy retina and improving treatment margins. With this treatment regimen, the patients experience improved visual outcomes and have a low rate of recurrence.

  20. Expansion of microvascular networks in vivo by phthalimide neovascular factor 1 (PNF1).

    Science.gov (United States)

    Wieghaus, Kristen A; Nickerson, Meghan M; Petrie Aronin, Caren E; Sefcik, Lauren S; Price, Richard J; Paige, Mikell A; Brown, Milton L; Botchwey, Edward A

    2008-12-01

    Phthalimide neovascular factor (PNF1, formerly SC-3-149) is a potent stimulator of proangiogenic signaling pathways in endothelial cells. In this study, we evaluated the in vivo effects of sustained PNF1 release to promote ingrowth and expansion of microvascular networks surrounding biomaterial implants. The dorsal skinfold window chamber was used to evaluate the structural remodeling response of the local microvasculature. PNF1 was released from poly(lactic-co-glycolic acid) (PLAGA) films, and a transport model was utilized to predict PNF1 penetration into the surrounding tissue. PNF1 significantly expanded microvascular networks within a 2mm radius from implants after 3 and 7 days by increasing microvessel length density and lumenal diameter of local arterioles and venules. Staining of histological sections with CD11b showed enhanced recruitment of circulating white blood cells, including monocytes, which are critical for the process of vessel enlargement through arteriogenesis. As PNF1 has been shown to modulate MT1-MMP, a facilitator of CCL2 dependent leukocyte transmigration, aspects of window chamber experiments were repeated in CCR2(-/-) (CCL2 receptor) mouse chimeras to more fully explore the critical nature of monocyte recruitment on the therapeutic benefits of PNF1 function in vivo.

  1. Extracellular superoxide dismutase deficiency impairs wound healing in advanced age by reducing neovascularization and fibroblast function.

    Science.gov (United States)

    Fujiwara, Toshihiro; Duscher, Dominik; Rustad, Kristine C; Kosaraju, Revanth; Rodrigues, Melanie; Whittam, Alexander J; Januszyk, Michael; Maan, Zeshaan N; Gurtner, Geoffrey C

    2016-03-01

    Advanced age is characterized by impairments in wound healing, and evidence is accumulating that this may be due in part to a concomitant increase in oxidative stress. Extended exposure to reactive oxygen species (ROS) is thought to lead to cellular dysfunction and organismal death via the destructive oxidation of intra-cellular proteins, lipids and nucleic acids. Extracellular superoxide dismutase (ecSOD/SOD3) is a prime antioxidant enzyme in the extracellular space that eliminates ROS. Here, we demonstrate that reduced SOD3 levels contribute to healing impairments in aged mice. These impairments include delayed wound closure, reduced neovascularization, impaired fibroblast proliferation and increased neutrophil recruitment. We further establish that SOD3 KO and aged fibroblasts both display reduced production of TGF-β1, leading to decreased differentiation of fibroblasts into myofibroblasts. Taken together, these results suggest that wound healing impairments in ageing are associated with increased levels of ROS, decreased SOD3 expression and impaired extracellular oxidative stress regulation. Our results identify SOD3 as a possible target to correct age-related cellular dysfunction in wound healing. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Inhibition of the recombinant human endostatin adenavirus on experimental choroidal neovascularization in rats

    Directory of Open Access Journals (Sweden)

    Li-Juan Chen

    2017-06-01

    Full Text Available AIM: To investigate the inhibition of the recombinant human endostatin adenavirus(Ad-Eson the experimental choroidal neovascularization(CNVmodels by intravitreous injection. METHODS: Experimental CNV models were induced by semiconductor laser in 30 male Brown Norway(BNrats and randomly divided into 3 groups with 10 rats in each group. At 21d after photocoagulation, the single administration group were given intravitreous injection with Ad-Es 0.01mL; the repeated administration group were given intravitreous injection with Ad-Es 0.01mL and a repeated injection 7d later; the saline control group were given intravitreous injection with saline 0.01mL. At 7d after final administration, the leakage of fundus fluorescein angiography(FFAwas observed. Various CNV areas were measured by using laser confocal microscopy of choroidal flatmount method. Pathology and ultrastructure were observed with light microscopy, the expressions of CD105 were measured by immunohistochemistry. RESULTS: The leakage of CNV of the administration group abviously decreased as compared with those in the saline group, the leakage of repeated administration group decreased compared with that of single administration group(PPCONCLUSION: Ad-Es can effectively inhibit semiconductor laser induced CNV in BN rats, and the inhibition effect of repeated administration group is better than that of single administration group. It may be a useful new method in the treatment of CNV.

  3. RECURRENCE OF CHOROIDAL NEOVASCULARIZATION LESION ACTIVITY AFTER AFLIBERCEPT TREATMENT FOR AGE-RELATED MACULAR DEGENERATION.

    Science.gov (United States)

    Wakazono, Tomotaka; Yamashiro, Kenji; Oishi, Akio; Ooto, Sotaro; Tamura, Hiroshi; Akagi-Kurashige, Yumiko; Hata, Masayuki; Takahashi, Ayako; Tsujikawa, Akitaka; Yoshimura, Nagahisa

    2017-11-01

    To examine the recurrence rate of choroidal neovascularization (CNV) lesion activity in age-related macular degeneration (AMD) and associated factors after 1-year aflibercept treatment. Age-related macular degeneration eyes with 1-year aflibercept fixed-regimen treatment and a follow-up period of at least 18 months from the initial aflibercept injection for treatment-naive exudative AMD were retrospectively evaluated. The recurrence rate was examined. Age, gender, visual acuity, AMD subtype, greatest linear dimension, and retinal and choroidal thicknesses at the 12th month examination were compared between eyes with and without recurrence. Presence of remnant polyps and pigment epithelial detachment (PED) morphology were also compared in polypoidal choroidal vasculopathy (PCV) eyes. Of the 98 eyes studied, 69 displayed a dry macula at the 12th month examination; 43.7% exhibited recurrence during the subsequent 12-month period in Kaplan-Meier analysis. Although no factors associated with recurrence were detected in AMD, remnant polyps and pigment epithelial detachment morphology at the 12th month examination were significantly associated with recurrence in polypoidal choroidal vasculopathy (P = 0.018 and 0.048, respectively). Continuous, proactive treatment would be considered overtreatment for more than half of the AMD eyes that achieved a dry macula. Angiography and optical coherence tomography analyses may be useful for predicting recurrence in polypoidal choroidal vasculopathy eyes.

  4. Hypoxia-induced retinal neovascularization in zebrafish embryos: a potential model of retinopathy of prematurity.

    Science.gov (United States)

    Wu, Yu-Ching; Chang, Chao-Yuan; Kao, Alex; Hsi, Brian; Lee, Shwu-Huey; Chen, Yau-Hung; Wang, I-Jong

    2015-01-01

    Retinopathy of prematurity, formerly known as a retrolental fibroplasia, is a leading cause of infantile blindness worldwide. Retinopathy of prematurity is caused by the failure of central retinal vessels to reach the retinal periphery, creating a nonperfused peripheral retina, resulting in retinal hypoxia, neovascularization, vitreous hemorrhage, vitreoretinal fibrosis, and loss of vision. We established a potential retinopathy of prematurity model by using a green fluorescent vascular endothelium zebrafish transgenic line treated with cobalt chloride (a hypoxia-inducing agent), followed by GS4012 (a vascular endothelial growth factor inducer) at 24 hours postfertilization, and observed that the number of vascular branches and sprouts significantly increased in the central retinal vascular trunks 2-4 days after treatment. We created an angiography method by using tetramethylrhodamine dextran, which exhibited severe vascular leakage through the vessel wall into the surrounding retinal tissues. The quantification of mRNA extracted from the heads of the larvae by using real-time quantitative polymerase chain reaction revealed a twofold increase in vegfaa and vegfr2 expression compared with the control group, indicating increased vascular endothelial growth factor signaling in the hypoxic condition. In addition, we demonstrated that the hypoxic insult could be effectively rescued by several antivascular endothelial growth factor agents such as SU5416, bevacizumab, and ranibizumab. In conclusion, we provide a simple, highly reproducible, and clinically relevant retinopathy of prematurity model based on zebrafish embryos; this model may serve as a useful platform for clarifying the mechanisms of human retinopathy of prematurity and its progression.

  5. FIVE-YEAR OUTCOMES OF INTRAVITREAL RANIBIZUMAB FOR CHOROIDAL NEOVASCULARIZATION IN PATIENTS WITH PATHOLOGIC MYOPIA.

    Science.gov (United States)

    Onishi, Yuka; Yokoi, Tae; Kasahara, Kaori; Yoshida, Takeshi; Nagaoka, Natsuko; Shinohara, Kosei; Kaneko, Yuichiro; Suga, Mitsuki; Uramoto, Kengo; Ohno-Tanaka, Akiko; Ohno-Matsui, Kyoko

    2018-05-03

    To determine the 5-year outcome of intravitreal ranibizumab (IVR) for myopic choroidal neovascularization (CNV). We retrospectively analyzed the medical records of 51 eyes of 51 consecutive patients with myopic CNV who had been treated with IVR with a minimum follow-up period of 5 years after the initial IVR injection. The factors that predicted the best-corrected visual acuity (BCVA) at 5 years after IVR were determined by multiple regression analysis. The mean age of the subjects was 63.6 years, and the mean axial length was 29.4 mm. The mean number of IVR was 1.6, and 34 eyes (66.7%) had only a single IVR. At the baseline and at the 1-year, 2-year, 4-year, and 5-year period, the mean BCVAs were 20/49, 20/37, 20/41, 20/45, and 20/42, respectively. Stepwise multiple regression analysis showed that the BCVA at 5-year period was significantly correlated with the baseline BCVA, the number of IVR injections, and the size of the CNV-related macular atrophy. Intravitreal ranibizumab provide a 5-year visual benefit in eyes with myopic CNV compared with the natural course. A lack of enlargement of the CNV-related macular atrophy, a better baseline BCVA, and a minimum number of IVR injections were associated with better visual outcomes.

  6. Effects of ginkgo biloba extract on laser-induced choroidal neovascularization in rats

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    Chao Chen

    2013-11-01

    Full Text Available AIM: To investigate the effects of ginkgo biloba extract(EGb 761on laser-induced choroidal neovascularization(CNVin rats.METHODS: Totally 60 BN rats were randomly divided into 4 groups: normal control group, model group, experimental group, physiological saline group with 15 in each group. All CNV models were made by krypton laser. Rats in experimental group were intraperitoneally injected with 0.35% EGb761(100mg/kgevery day after laser exposure until they were sacrificed. Rats in physiological saline group were intraperitoneally injected physiological saline every day after laser exposure until they were sacrificed. Fundus fluorescein angiography(FFAwas performed on every rat on the 7th day, 14th day and the 21st day after laser exposure, then the rats were sacrificed immediately. The eyes were enucleated and processed for histopathologic examination.RESULTS: There was no choroidal fluorescein leakage staining in normal rats. There were obviously less choroidal fluorescein leakage points in experimental groups than that in the corresponding model groups(PCONCLUSION: EGb761 len inhibit the formation of laser-induced CNV in rats. The longer the time, the better curative effect.

  7. An experimental study on choroidal neovascularization induced by Krypton laser in rat model.

    Science.gov (United States)

    Cui, Jing; Liu, Yuanyuan; Zhang, Jingkai; Yan, Hua

    2014-01-01

    The purpose of this work was to study the efficacy and safety of choroidal neovascularization (CNV) formation induced by Krypton laser in Brown Norway (BN) rats, and observe the trend of the change of CNV after laser photocoagulation. Twenty-five male BN rats were involved in this study. Two eyes of one rat without any laser photocoagulation were randomly selected as the control group, and the other 48 eyes of 24 rats were selected as the experimental group. Eight eyes of four rats were randomly selected to receive the examinations of fundus fluorescein angiography (FFA), histopathology, and transmission electron microscopy 3, 7, 14, 21, 28, and 56 days after laser photocoagulation. After laser photocoagulation, the leakage appeared in burns on day 7 (59%), reached the peak on day 21 (84%), (p0.05). The thickness of CNV increased from day 7 to day 21 (p0.05). The experimental model of CNV can be successfully induced by Krypton laser in rats with a stable, long-lasting, and high success rate. After laser photocoagulation, the leakages appear on day 7, reach the peak on day 21, and remain stable after day 21.

  8. Optical Coherence Tomography Angiography in Retinal Vascular Diseases and Choroidal Neovascularization

    Directory of Open Access Journals (Sweden)

    Rodolfo Mastropasqua

    2015-01-01

    Full Text Available Purpose. To assess the ability of optical coherence tomography-angiography (OCT-A to show and analyze retinal vascular patterns and the choroidal neovascularization (CNV in retinal vascular diseases. Methods. Seven eyes of seven consecutive patients with retinal vascular diseases were examined. Two healthy subjects served as controls. All eyes were scanned with the SD-OCT XR Avanti (Optovue Inc, Fremont CA, USA. Split spectrum amplitude decorrelation angiography algorithm was used to identify the blood flow within the tissue. Fluorescein angiography (FA and indocyanine green angiography (ICGA with Spectralis HRA + OCT (Heidelberg Engineering GmbH were performed. Results. In healthy subjects OCT-A visualized major macular vessels and detailed capillary networks around the foveal avascular zone. Patients were affected with myopic CNV (2 eyes, age-related macular degeneration related (2, branch retinal vein occlusion (BRVO (2, and branch retinal artery occlusion (BRAO (1. OCT-A images provided distinct vascular patterns, distinguishing perfused and nonperfused areas in BRVO and BRAO and recognizing the presence, location, and size of CNV. Conclusions. OCT-A provides detailed images of retinal vascular plexuses and quantitative data of pathologic structures. Further studies are warranted to define the role of OCT-A in the assessment of retinovascular diseases, with respect to conventional FA and ICG-A.

  9. Detection of neovascularization based on fractal and texture analysis with interaction effects in diabetic retinopathy.

    Science.gov (United States)

    Lee, Jack; Zee, Benny Chung Ying; Li, Qing

    2013-01-01

    Diabetic retinopathy is a major cause of blindness. Proliferative diabetic retinopathy is a result of severe vascular complication and is visible as neovascularization of the retina. Automatic detection of such new vessels would be useful for the severity grading of diabetic retinopathy, and it is an important part of screening process to identify those who may require immediate treatment for their diabetic retinopathy. We proposed a novel new vessels detection method including statistical texture analysis (STA), high order spectrum analysis (HOS), fractal analysis (FA), and most importantly we have shown that by incorporating their associated interactions the accuracy of new vessels detection can be greatly improved. To assess its performance, the sensitivity, specificity and accuracy (AUC) are obtained. They are 96.3%, 99.1% and 98.5% (99.3%), respectively. It is found that the proposed method can improve the accuracy of new vessels detection significantly over previous methods. The algorithm can be automated and is valuable to detect relatively severe cases of diabetic retinopathy among diabetes patients.

  10. Detection of neovascularization based on fractal and texture analysis with interaction effects in diabetic retinopathy.

    Directory of Open Access Journals (Sweden)

    Jack Lee

    Full Text Available Diabetic retinopathy is a major cause of blindness. Proliferative diabetic retinopathy is a result of severe vascular complication and is visible as neovascularization of the retina. Automatic detection of such new vessels would be useful for the severity grading of diabetic retinopathy, and it is an important part of screening process to identify those who may require immediate treatment for their diabetic retinopathy. We proposed a novel new vessels detection method including statistical texture analysis (STA, high order spectrum analysis (HOS, fractal analysis (FA, and most importantly we have shown that by incorporating their associated interactions the accuracy of new vessels detection can be greatly improved. To assess its performance, the sensitivity, specificity and accuracy (AUC are obtained. They are 96.3%, 99.1% and 98.5% (99.3%, respectively. It is found that the proposed method can improve the accuracy of new vessels detection significantly over previous methods. The algorithm can be automated and is valuable to detect relatively severe cases of diabetic retinopathy among diabetes patients.

  11. Variability of disease activity in patients treated with ranibizumab for neovascular age-related macular degeneration.

    Science.gov (United States)

    Enders, P; Scholz, P; Muether, P S; Fauser, S

    2016-08-01

    PurposeTo analyze choroidal neovasularization (CNV) activity and recurrence patterns in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab, and the correlation with individual intraocular vascular endothelial growth factor (VEGF) suppression time (VST).MethodsPost-hoc analysis of data from a prospective, non-randomized clinical study. Patients with nAMD treated with ranibizumab on a pro re nata regimen. Disease activity was analyzed monthly by spectral-domain optical coherence tomography and correlated with VSTs.ResultsOverall, 73 eyes of 73 patients were included in the study with a mean follow-up of 717 days (range: 412-1239 days). Overall, the mean CNV-activity-free interval was 76.5 days (range: 0-829 days). The individual range of the length of dry intervals was high. A total of 42% of patients had a range of more than 90 days. Overall, 16% of patients showed persistent activity. And 12% stayed dry after the initial ranibizumab treatment. No significant correlation was found between the CNV-recurrence pattern and VST (P=0.12).ConclusionsCNV activity in nAMD is irregular, which is reflected in the range of the duration of dry intervals and late recurrences. The biomarker VST solely seems not to be sufficient to explain recurrence pattern of CNV in all AMD patients.

  12. Caregiver Burden in Patients Receiving Ranibizumab Therapy for Neovascular Age Related Macular Degeneration.

    Directory of Open Access Journals (Sweden)

    Rishma Gohil

    Full Text Available To assess the caregiver burden and factors determining the burden in patients receiving ranibizumab therapy for neovascular AMD (nAMD.This is a cross-sectional questionnaire survey of 250 matched patient caregiver dyads across three large ophthalmic treatment centres in United Kingdom. The primary outcome was the subjective caregiver burden measured using caregiver reaction assessment scale (CRA. Objective caregiver burden was determined by the caregiver tasks and level of care provided. The factors that may predict the caregiver burden such as the patient's visual acuity of the better eye and vision related quality of life, demographics, satisfaction and support provided by the healthcare and the health status of the dyads were also collected and assessed in a hierarchical regression model.The mean CRA score was 3.2±0.5, similar to the score reported by caregivers for atrial fibrillation who require regular hospital appointments for monitoring their thromboprophylaxis. Caregiver tasks including accompanying for hospital appointments for eye treatment and patient's visual acuity in the better eye were the biggest contributors to the caregiver burden hierarchical model explaining 18% and 11% of the variance respectively.Ranibizumab therapy for nAMD is associated with significant caregiver burden. Both disease impact and treatment frequency contributed to the overall burden.

  13. Targeting NCK-Mediated Endothelial Cell Front-Rear Polarity Inhibits Neovascularization.

    Science.gov (United States)

    Dubrac, Alexandre; Genet, Gael; Ola, Roxana; Zhang, Feng; Pibouin-Fragner, Laurence; Han, Jinah; Zhang, Jiasheng; Thomas, Jean-Léon; Chedotal, Alain; Schwartz, Martin A; Eichmann, Anne

    2016-01-26

    Sprouting angiogenesis is a key process driving blood vessel growth in ischemic tissues and an important drug target in a number of diseases, including wet macular degeneration and wound healing. Endothelial cells forming the sprout must develop front-rear polarity to allow sprout extension. The adaptor proteins Nck1 and 2 are known regulators of cytoskeletal dynamics and polarity, but their function in angiogenesis is poorly understood. Here, we show that the Nck adaptors are required for endothelial cell front-rear polarity and migration downstream of the angiogenic growth factors VEGF-A and Slit2. Mice carrying inducible, endothelial-specific Nck1/2 deletions fail to develop front-rear polarized vessel sprouts and exhibit severe angiogenesis defects in the postnatal retina and during embryonic development. Inactivation of NCK1 and 2 inhibits polarity by preventing Cdc42 and Pak2 activation by VEGF-A and Slit2. Mechanistically, NCK binding to ROBO1 is required for both Slit2- and VEGF-induced front-rear polarity. Selective inhibition of polarized endothelial cell migration by targeting Nck1/2 prevents hypersprouting induced by Notch or Bmp signaling inhibition, and pathological ocular neovascularization and wound healing, as well. These data reveal a novel signal integration mechanism involving NCK1/2, ROBO1/2, and VEGFR2 that controls endothelial cell front-rear polarity during sprouting angiogenesis. © 2015 American Heart Association, Inc.

  14. Targeting NCK-Mediated Endothelial Cell Front-Rear Polarity Inhibits Neo-Vascularization

    Science.gov (United States)

    Dubrac, Alexandre; Genet, Gael; Ola, Roxana; Zhang, Feng; Pibouin-Fragner, Laurence; Han, Jinah; Zhang, Jiasheng; Thomas, Jean-Léon; Chedotal, Alain; Schwartz, Martin A.; Eichmann, Anne

    2015-01-01

    Background Sprouting angiogenesis is a key process driving blood vessel growth in ischemic tissues and an important drug target in a number of diseases, including wet macular degeneration and wound healing. Endothelial cells forming the sprout must develop front-rear polarity to allow sprout extension. The adaptor proteins Nck1 and 2 are known regulators of cytoskeletal dynamics and polarity, but their function in angiogenesis is poorly understood. Here we show that the Nck adaptors are required for endothelial cell front-rear polarity and migration downstream of the angiogenic growth factors VEGF-A and Slit2. Methods and Results Mice carrying inducible, endothelial-specific Nck1/2 deletions fail to develop front-rear polarized vessel sprouts and exhibit severe angiogenesis defects in the postnatal retina and during embryonic development. Inactivation of NCK1 and 2 inhibits polarity by preventing Cdc42 and Pak2 activation by VEGF-A and Slit2. Mechanistically, NCK binding to ROBO1 is required for both Slit2 and VEGF induced front-rear polarity. Selective inhibition of polarized endothelial cell migration by targeting Nck1/2 prevents hypersprouting induced by Notch or Bmp signaling inhibition, as well as pathological ocular neovascularization and wound healing. Conclusions These data reveal a novel signal integration mechanism involving NCK1/2, ROBO1/2 and VEGFR2 that controls endothelial cell front-rear polarity during sprouting angiogenesis. PMID:26659946

  15. The Robo4 cytoplasmic domain is dispensable for vascular permeability and neovascularization.

    Science.gov (United States)

    Zhang, Feng; Prahst, Claudia; Mathivet, Thomas; Pibouin-Fragner, Laurence; Zhang, Jiasheng; Genet, Gael; Tong, Raymond; Dubrac, Alexandre; Eichmann, Anne

    2016-11-24

    Vascular permeability and neovascularization are implicated in many diseases including retinopathies and diabetic wound healing. Robo4 is an endothelial-specific transmembrane receptor that stabilizes the vasculature, as shown in Robo4 -/- mice that develop hyperpermeability, but how Robo4 signals remained unclear. Here we show that Robo4 deletion enhances permeability and revascularization in oxygen-induced retinopathy (OIR) and accelerates cutaneous wound healing. To determine Robo4 signalling pathways, we generated transgenic mice expressing a truncated Robo4 lacking the cytoplasmic domain (Robo4ΔCD). Robo4ΔCD expression is sufficient to prevent permeability, and inhibits OIR revascularization and wound healing in Robo4 -/- mice. Mechanistically, Robo4 does not affect Slit2 signalling, but Robo4 and Robo4ΔCD counteract Vegfr2-Y949 (Y951 in human VEGFR2) phosphorylation by signalling through the endothelial UNC5B receptor. We conclude that Robo4 inhibits angiogenesis and vessel permeability independently of its cytoplasmic domain, while activating VEGFR2-Y951 via ROBO4 inhibition might accelerate tissue revascularization in retinopathy of prematurity and in diabetic patients.

  16. Role of macular xanthophylls in prevention of common neovascular retinopathies: retinopathy of prematurity and diabetic retinopathy.

    Science.gov (United States)

    Gong, Xiaoming; Rubin, Lewis P

    2015-04-15

    Retinopathy of prematurity (ROP) and diabetic retinopathy (DR) are important causes of blindness among children and working-age adults, respectively. The development of both diseases involves retinal microvascular degeneration, vessel loss and consequent hypoxic and inflammatory pathologic retinal neovascularization. Mechanistic studies have shown that oxidative stress and subsequent derangement of cell signaling are important factors in disease progression. In eye and vision research, role of the dietary xanthophyll carotenoids, lutein and zeaxanthin, has been more extensively studied in adult onset macular degeneration than these other retinopathies. These carotenoids also may decrease severity of ROP in preterm infants and of DR in working-age adults. A randomized controlled clinical trial of carotenoid supplementation in preterm infants indicated that lutein has functional effects in the neonatal eye and is anti-inflammatory. Three multicenter clinical trials all showed a trend of decreased ROP severity in the lutein supplemented group. Prospective studies on patients with non-proliferative DR indicate serum levels of lutein and zeaxanthin are significantly lower in these patients compared to normal subjects. The present review describes recent advances in lutein and zeaxanthin modulation of oxidative stress and inflammation related to ROP and DR and discusses potential roles of lutein/zeaxanthin in preventing or lessening the risks of disease initiation or progression. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Effect of combined topical heparin and steroid on corneal neovascularization in children.

    Science.gov (United States)

    Michels, Rike; Michels, Stephan; Kaminski, Stephan

    2012-01-01

    To demonstrate the effect of topical heparin combined with topical steroid on corneal neovascularization (CN) in children. Four children (5 eyes) with new-onset progressive CN in at least one eye received topical rimexolone or dexamethasone in combination with heparin until complete regression of CN was obtained. The regression of CN was documented by slit-lamp or anterior segment photography. All 5 eyes showed complete regression of CN within 5 months. An anti-angiogenic effect was found as early as 1 week after starting topical combination treatment. No ocular and systemic side effects were detected and treatment was well tolerated by all children. In the 3 eyes with involvement of the optical axis, symmetrical visual acuity was obtained by amblyopia treatment. Recurrence of the CN was detectable in 2 eyes at 1 and 6 months, respectively, after ending combination therapy. Both eyes responded favorably to re-treatment. Combination of topical heparin and steroid leads to rapid regression and complete inactivity of CN. This therapeutic approach is promising, especially in children with limited therapeutic alternatives and a high risk for amblyopia. Copyright 2012, SLACK Incorporated.

  18. Visual function after strontium-90 plaque irradiation in patients with age-related subfoveal choroidal neovascularization

    Energy Technology Data Exchange (ETDEWEB)

    Jaakkola, A.; Tarkkanen, A.; Immonen, I. [Helsinki Univ. Central Hospital, Dept. of Ophthalmology (Finland); Heikkonen, J. [Helsinki Univ. Central Hospital, Dept. of Oncology (Finland)

    1999-05-01

    Purpose: To report 2-year visual and angiographic results in eyes treated with strontium plaque irradiation for subfoveal choroidal neovascular membranes (CNVM) in age-related macular degeneration. Methods: Twenty eyes with recent subfoveal CNVM were treated with local irradiation. The impact of the treatment on visual function was evaluated by visual acuity, contrast sensitivity and reading speed testing. Results: At 12 months visual acuity had improved or remained the same in 9/20 eyes (45%). At 24 months visual acuity was stable in 5/18 eyes (28%). Eyes with signs of CNVM regression (13/18,72%) lost a mean of 3.3 lines, but eyes with recurrent CNVM lost a mean of 5.1 lines of vision. The mean contrast sensitivity was better in the irradiated eyes than in the fellow eyes with late age-related macular degeneration at 24 months. Six of 17 irradiated eyes (35%) could read at least some words at 24 months. Conclusion: Visual function decreases in patients treated with strontium irradiation, but less in eyes showing regression of the CNVM than in eyes with further growth of the CNVM. (au) 20 refs.

  19. Influence of new societal factors on neovascular age-related macular degeneration outcomes.

    Science.gov (United States)

    Giocanti-Aurégan, Audrey; Chbat, Elige; Darugar, Adil; Morel, Christophe; Morin, Bruno; Conrath, John; Devin, François

    2018-02-01

    To assess the impact of unstudied societal factors for neovascular age-related macular degeneration (nAMD) on functional outcomes after anti-VEGFs. Charts of 94 nAMD patients treated in the Monticelli-Paradis Centre, Marseille, France, were reviewed. Phone interviews were conducted to assess societal factors, including transportation, living status, daily reading and social security scheme (SSS). Primary outcome was the impact of family support and disease burden on functional improvement in nAMD. Between baseline and month 24 (M24), 42.4% of the variability in best-corrected visual acuity (BCVA) was explained by the cumulative effect of the following societal factors: intermittent out-patient follow-up, marital status, daily reading, transportation type, commuting time. No isolated societal factor significantly correlated with ETDRS BCVA severity at M24. A trend to correlation was observed between the EDTRS score at M24 and the SSS (P = 0.076), economic burden (P = 0.075), time between diagnosis and treatment initiation (P = 0.070). A significant correlation was found for the disease burdensome on the patient (P = 0.034) and low vision rehabilitation (P = 0.014). Societal factors could influence functional outcomes in nAMD patients treated with anti-VEGFs. They could contribute to the healing process or sustain disease progression.

  20. Submacular hemorrhage in neovascular age-related macular degeneration: A synthesis of the literature.

    Science.gov (United States)

    Stanescu-Segall, Dinu; Balta, Florian; Jackson, Timothy L

    2016-01-01

    Large submacular hemorrhage, an uncommon manifestation of neovascular age-related macular degeneration, may also occur with idiopathic polypoidal choroidal vasculopathy. Submacular hemorrhage damages photoreceptors owing to iron toxicity, fibrin meshwork contraction, and reduced nutrient flux, with subsequent macular scarring. Clinical and experimental studies support prompt treatment, as tissue damage can occur within 24 hours. Without treatment the natural history is poor, with a mean final visual acuity (VA) of 20/1600. Reported treatments include retinal pigment epithelial patch, macular translocation, pneumatic displacement, intravitreal or subretinal tissue plasminogen activator, intravitreal anti-vascular endothelial growth factor (VEGF) drugs, and combinations thereof. In the absence of comparative studies, we combined eligible studies to assess the VA change before and after each treatment option. The greatest improvement occurred after combined pars plana vitrectomy, subretinal tissue plasminogen activator, intravitreal gas, and anti-vascular endothelial growth factor treatment, with VA improving from 20/1000 to 20/400. The best final VA occurred using combined intravitreal tissue plasminogen activator, gas, and anti-vascular endothelial growth factor therapy, with VA improving from 20/200 to 20/100. Both treatments had an acceptable safety profile, but most studies were small, and larger randomized controlled trials are needed to determine both safety and efficacy. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  1. Fasudil hydrochloride, a potent ROCK inhibitor, inhibits corneal neovascularization after alkali burns in mice

    Science.gov (United States)

    Zeng, Peng; Pi, Rong-biao; Li, Peng; Chen, Rong-xin; Lin, Li-mian; He, Hong

    2015-01-01

    Purpose To investigate the effects and mechanisms of fasudil hydrochloride (fasudil) on and in alkali burn-induced corneal neovascularization (CNV) in mice. Methods To observe the effect of fasudil, mice with alkali-burned corneas were treated with either fasudil eye drops or phosphate-buffered saline (PBS) four times per day for 14 consecutive days. After injury, CNV and corneal epithelial defects were measured. The production of reactive oxygen species (ROS) and heme oxygenase-1(HO-1) was measured. The infiltration of polymorphonuclear neutrophils (PMNs) and the mRNA expressions of CNV-related genes were analyzed on day 14. Results The incidence of CNV was significantly lower after treatment with 100 μM and 300 μM fasudil than with PBS, especially with 100 μM fasudil. Meanwhile, the incidences of corneal epithelial defects was lower (n=15, all palkali burn-induced CNV and promote the healing of corneal epithelial defects in mice. These effects are attributed to a decrease in inflammatory cell infiltration, reduction of ROS, and upregulation of HO-1 protein after fasudil treatment. PMID:26120273

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  5. Regulation of Mammary Progenitor Cells by p53 and Parity

    Science.gov (United States)

    2011-01-01

    quantitative PCR system (Stratagene). To knockdown Notch1 in TM40A cells, siRNA (s70698 and s70700) were purchased from Ambion. s70698 siRNA sense sequence: 5...hours after transfect ion and real-tim e quantitative P CR was used to confirm the knockdown efficiency. Results Label and chase progenitor cells...cells contained 0.8% o f DsRed positiv e (DsR +) progenitor cells (Fig. 1B). The mammosphere-forming capacity of DsR+ cells is 3.8-fold greater

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  6. File list: Pol.Neu.50.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

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  19. Bevacizumab (Avastin® no tratamento da membrana neovascular coroidal secundária à degeneração macular relacionada à idade: relato de caso Bevacizumab (Avastin® in treatment of choroidal neovascularization secondary to age-related macular degeneration: a case report

    Directory of Open Access Journals (Sweden)

    Tiago Eugênio Faria e Arantes

    2007-12-01

    Full Text Available As drogas anti-angiogênicas foram introduzidas recentemente no arsenal terapêutico das membranas neovasculares coroidais. O objetivo deste relato é descrever um caso de membranas neovasculares coroidais oculta com extenso descolamento do epitélio pigmentado da retina, tratada com bevacizumab (Avastin® intravítrea. A eficácia da medicação foi avaliada por meio da acuidade visual e de exames complementares (angiografia fluoresceínica, videoangiografia com indocianina verde e tomografia de coerência óptica. Após três injeções intravítreas de bevacizumab, obteve-se uma resposta anatômica e visual satisfatória, denotando benefícios da droga, apesar do extenso descolamento do epitélio pigmentado da retina associada a membranas neovasculares coroidais oculta.The antiangiogenic drugs have been recently introduced in the therapeutic armamentarium of choroidal neovascularization. The purpose of this report is to describe a case of occult choroidal neovascularization with extensive retinal pigment epithelial detachment treated with intravitreal bevacizumab (Avastin®. The efficacy of the medication was evaluated by means of visual acuity and complementary exams (fluorescein angiography, indocyanine green video angiography and optical coherence tomography. After three intravitreal injections of bevacizumab a satisfactory anatomic and visual response was achieved, showing benefits of the drug, despite the extensive retinal pigment epithelial detachment associated with occult choroidal neovascularization.

  20. Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Juan Antonio Guadix

    2017-12-01

    Full Text Available Summary: Human pluripotent stem cells (hPSCs are widely used to study cardiovascular cell differentiation and function. Here, we induced differentiation of hPSCs (both embryonic and induced to proepicardial/epicardial progenitor cells that cover the heart during development. Addition of retinoic acid (RA and bone morphogenetic protein 4 (BMP4 promoted expression of the mesodermal marker PDGFRα, upregulated characteristic (proepicardial progenitor cell genes, and downregulated transcription of myocardial genes. We confirmed the (proepicardial-like properties of these cells using in vitro co-culture assays and in ovo grafting of hPSC-epicardial cells into chick embryos. Our data show that RA + BMP4-treated hPSCs differentiate into (proepicardial-like cells displaying functional properties (adhesion and spreading over the myocardium of their in vivo counterpart. The results extend evidence that hPSCs are an excellent model to study (proepicardial differentiation into cardiovascular cells in human development and evaluate their potential for cardiac regeneration. : The authors have shown that hPSCs can be instructed in vitro to differentiate into a specific cardiac embryonic progenitor cell population called the proepicardium. Proepicardial cells are required for normal formation of the heart during development and might contribute to the development of cell-based therapies for heart repair. Keywords: human pluripotent stem cells, proepicardium, progenitor cells, cardiovascular, differentiation

  1. Cellular therapy after spinal cord injury using neural progenitor cells

    NARCIS (Netherlands)

    Vroemen, Maurice

    2006-01-01

    In this thesis, the possibilities and limitations of cell-based therapies after spinal cord injury are explored. Particularly, the potential of adult derived neural progenitor cell (NPC) grafts to function as a permissive substrate for axonal regeneration was investigated. It was found that syngenic

  2. Progenitor cells in the kidney: biology and therapeutic perspectives

    NARCIS (Netherlands)

    Rookmaaker, M.B.; Verhaar, M.C.; Zonneveld, A.J. van; Rabelink, T.J.

    2004-01-01

    Progenitor cells in the kidney: Biology and therapeutic perspectives. The stem cell may be viewed as an engineer who can read the blue print and become the building. The role of this fascinating cell in physiology and pathophysiology has recently attracted a great deal of interest. The archetype of

  3. Long GRBs from binary stars: runaway, Wolf-Rayet progenitors

    NARCIS (Netherlands)

    Cantiello, M.; Yoon, S.C.; Langer, N.; Livio, M.

    2007-01-01

    The collapsar model for long gamma-ray bursts requires a rapidly rotating Wolf-Rayet star as progenitor. We test the idea of producing rapidly rotating Wolf-Rayet stars in massive close binaries through mass accretion and consecutive quasi-chemically homogeneous evolution — the latter had previously

  4. Long GRBs from Binary Stars: Runaway, Wolf-Rayet Progenitors

    NARCIS (Netherlands)

    Cantiello, M.; Yoon, S.C.; Langer, N.; Livio, M.

    2007-01-01

    The collapsar model for long gamma-ray bursts requires a rapidly rotating Wolf-Rayet star as progenitor. We test the idea of producing rapidly rotating Wolf-Rayet stars in massive close binaries through mass accretion and consecutive quasi-chemically homogeneous evolution - the latter had previously

  5. Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors

    DEFF Research Database (Denmark)

    Paul, Franziska; Arkin, Ya'ara; Giladi, Amir

    2015-01-01

    Within the bone marrow, stem cells differentiate and give rise to diverse blood cell types and functions. Currently, hematopoietic progenitors are defined using surface markers combined with functional assays that are not directly linked with in vivo differentiation potential or gene regulatory m...

  6. Intersections of lung progenitor cells, lung disease and lung cancer.

    Science.gov (United States)

    Kim, Carla F

    2017-06-30

    The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials. Copyright ©ERS 2017.

  7. Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor Cells

    NARCIS (Netherlands)

    Guadix, Juan Antonio; Orlova, Valeria V.; Giacomelli, Elisa; Bellin, Milena; Ribeiro, Marcelo C.; Mummery, Christine L.; Pérez-Pomares, José M.; Passier, Robert

    2017-01-01

    Human pluripotent stem cells (hPSCs) are widely used to study cardiovascular cell differentiation and function. Here, we induced differentiation of hPSCs (both embryonic and induced) to proepicardial/epicardial progenitor cells that cover the heart during development. Addition of retinoic acid (RA)

  8. Mobilization of hematopoietic stem and progenitor cells in mice

    NARCIS (Netherlands)

    Robinson, Simon N; van Os, Ronald P; Bunting, Kevin

    2008-01-01

    Animal models have added significantly to our understanding of the mechanism(s) of hematopoietic stem and progenitor cell (HSPC) mobilization. Such models suggest that changes in the interaction between the HSPC and the hematopoietic microenvironmental 'niche' (cellular and extracellular components)

  9. The progenitor of Nova Cygni 2006 (=V2362 Cyg)

    NARCIS (Netherlands)

    Steeghs, D.; Greimel, R.; Drew, J.; Irwin, M.; Gaensicke, B.; Groot, P.J.; Knigge, C.

    2006-01-01

    We report on the detection of the likely progenitor to Nova Cygni 2006 = V2362 Cyg (IAUC #8697, #8698, ATel #792) using images from the INT Photometric H-Alpha Survey (IPHAS; http://www.iphas.org). The field containing the classical nova was observed as part of our galactic plane survey on Aug. 3rd

  10. Retinal progenitor cell xenografts to the pig retina

    DEFF Research Database (Denmark)

    Warfvinge, Karin; Kiilgaard, Jens Folke; Klassen, Henry

    2006-01-01

    We evaluated the host response to murine retinal progenitor cells (RPCs) following transplantation to the subretinal space (SRS) of the pig. RPCs from GFP mice were transplanted subretinally in 18 nonimmunosuppressed normal or laser-treated pigs. Evaluation of the SRS was performed on hematoxylin-eosin...

  11. Mass ejection in failed supernovae: variation with stellar progenitor

    Science.gov (United States)

    Fernández, Rodrigo; Quataert, Eliot; Kashiyama, Kazumi; Coughlin, Eric R.

    2018-05-01

    We study the ejection of mass during stellar core-collapse when the stalled shock does not revive and a black hole forms. Neutrino emission during the protoneutron star phase causes a decrease in the gravitational mass of the core, resulting in an outward going sound pulse that steepens into a shock as it travels out through the star. We explore the properties of this mass ejection mechanism over a range of stellar progenitors using spherically symmetric, time-dependent hydrodynamic simulations that treat neutrino mass-loss parametrically and follow the shock propagation over the entire star. We find that all types of stellar progenitor can eject mass through this mechanism. The ejected mass is a decreasing function of the surface gravity of the star, ranging from several M⊙ for red supergiants to ˜0.1 M⊙ for blue supergiants and ˜10-3 M⊙ for Wolf-Rayet stars. We find that the final shock energy at the surface is a decreasing function of the core-compactness, and is ≲ 1047-1048 erg in all cases. In progenitors with a sufficiently large envelope, high core-compactness, or a combination of both, the sound pulse fails to unbind mass. Successful mass ejection is accompanied by significant fallback accretion that can last from hours to years. We predict the properties of shock breakout and thermal plateau emission produced by the ejection of the outer envelope of blue supergiant and Wolf-Rayet progenitors in otherwise failed supernovae.

  12. Hmga2 regulates self-renewal of retinal progenitors.

    Science.gov (United States)

    Parameswaran, Sowmya; Xia, Xiaohuan; Hegde, Ganapati; Ahmad, Iqbal

    2014-11-01

    In vertebrate retina, histogenesis occurs over an extended period. To sustain the temporal generation of diverse cell types, retinal progenitor cells (RPCs) must self-renew. However, self-renewal and regulation of RPCs remain poorly understood. Here, we demonstrate that cell-extrinsic factors coordinate with the epigenetic regulator high-mobility group AT-hook 2 (Hmga2) to regulate self-renewal of late retinal progenitor cells (RPCs). We observed that a small subset of RPCs was capable of clonal propagation and retained multipotentiality of parents in the presence of endothelial cells (ECs), known self-renewal regulators in various stem cell niches. The self-renewing effects, also observed in vivo, involve multiple intercellular signaling pathways, engaging Hmga2. As progenitors exhaust during retinal development, expression of Hmga2 progressively decreases. Analyses of Hmga2-expression perturbation, in vitro and in vivo, revealed that Hmga2 functionally helps to mediate cell-extrinsic influences on late-retinal progenitor self-renewal. Our results provide a framework for integrating the diverse intercellular influences elicited by epigenetic regulators for self-renewal in a dynamic stem cell niche: the developing vertebrate retina. © 2014. Published by The Company of Biologists Ltd.

  13. Intersections of lung progenitor cells, lung disease and lung cancer

    Directory of Open Access Journals (Sweden)

    Carla F. Kim

    2017-06-01

    Full Text Available The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials.

  14. Characteristics of meniscus progenitor cells migrated from injured meniscus.

    Science.gov (United States)

    Seol, Dongrim; Zhou, Cheng; Brouillette, Marc J; Song, Ino; Yu, Yin; Choe, Hyeong Hun; Lehman, Abigail D; Jang, Kee W; Fredericks, Douglas C; Laughlin, Barbara J; Martin, James A

    2017-09-01

    Serious meniscus injuries seldom heal and increase the risk for knee osteoarthritis; thus, there is a need to develop new reparative therapies. In that regard, stimulating tissue regeneration by autologous stem/progenitor cells has emerged as a promising new strategy. We showed previously that migratory chondrogenic progenitor cells (CPCs) were recruited to injured cartilage, where they showed a capability in situ tissue repair. Here, we tested the hypothesis that the meniscus contains a similar population of regenerative cells. Explant studies revealed that migrating cells were mainly confined to the red zone in normal menisci: However, these cells were capable of repopulating defects made in the white zone. In vivo, migrating cell numbers increased dramatically in damaged meniscus. Relative to non-migrating meniscus cells, migrating cells were more clonogenic, overexpressed progenitor cell markers, and included a larger side population. Gene expression profiling showed that the migrating population was more similar to CPCs than other meniscus cells. Finally, migrating cells equaled CPCs in chondrogenic potential, indicating a capacity for repair of the cartilaginous white zone of the meniscus. These findings demonstrate that, much as in articular cartilage, injuries to the meniscus mobilize an intrinsic progenitor cell population with strong reparative potential. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1966-1972, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  15. TYPE IIb SUPERNOVAE WITH COMPACT AND EXTENDED PROGENITORS

    International Nuclear Information System (INIS)

    Chevalier, Roger A.; Soderberg, Alicia M.

    2010-01-01

    The classic example of a Type IIb supernova is SN 1993J, which had a cool extended progenitor surrounded by a dense wind. There is evidence for another category of Type IIb supernova that has a more compact progenitor with a lower density, probably fast, wind. Distinguishing features of the compact category are weak optical emission from the shock heated envelope at early times, nonexistent or very weak H emission in the late nebular phase, rapidly evolving radio emission, rapid expansion of the radio shell, and expected nonthermal as opposed to thermal X-ray emission. Type IIb supernovae that have one or more of these features include SNe 1996cb, 2001ig, 2003bg, 2008ax, and 2008bo. All of these with sufficient radio data (the last four) show evidence for presupernova wind variability. We estimate a progenitor envelope radius ∼1 x 10 11 cm for SN 2008ax, a value consistent with a compact Wolf-Rayet progenitor. Supernovae in the SN 1993J extended category include SN 2001gd and probably the Cas A supernova. We suggest that the compact Type IIb events be designated Type cIIb and the extended ones Type eIIb. The H envelope mass dividing these categories is ∼0.1 M sun .

  16. Cardiac stem/progenitor cells, secreted proteins, and proteomics

    Czech Academy of Sciences Publication Activity Database

    Šťastná, Miroslava; Abraham, M.R.; Van Eyk, J.E.

    2009-01-01

    Roč. 583, č. 11 (2009), s. 1800-1807 ISSN 0014-5793 Institutional research plan: CEZ:AV0Z40310501 Keywords : Cardiac stem/progenitor cell * paracrine factor * secretome Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.541, year: 2009

  17. Optimization of an Image-Guided Laser-Induced Choroidal Neovascularization Model in Mice.

    Directory of Open Access Journals (Sweden)

    Yan Gong

    Full Text Available The mouse model of laser-induced choroidal neovascularization (CNV has been used in studies of the exudative form of age-related macular degeneration using both the conventional slit lamp and a new image-guided laser system. A standardized protocol is needed for consistent results using this model, which has been lacking. We optimized details of laser-induced CNV using the image-guided laser photocoagulation system. Four lesions with similar size were consistently applied per eye at approximately double the disc diameter away from the optic nerve, using different laser power levels, and mice of various ages and genders. After 7 days, the mice were sacrificed and retinal pigment epithelium/choroid/sclera was flat-mounted, stained with Isolectin B4, and imaged. Quantification of the area of the laser-induced lesions was performed using an established and constant threshold. Exclusion criteria are described that were necessary for reliable data analysis of the laser-induced CNV lesions. The CNV lesion area was proportional to the laser power levels. Mice at 12-16 weeks of age developed more severe CNV than those at 6-8 weeks of age, and the gender difference was only significant in mice at 12-16 weeks of age, but not in those at 6-8 weeks of age. Dietary intake of omega-3 long-chain polyunsaturated fatty acid reduced laser-induced CNV in mice. Taken together, laser-induced CNV lesions can be easily and consistently applied using the image-guided laser platform. Mice at 6-8 weeks of age are ideal for the laser-induced CNV model.

  18. Theme trends and knowledge structure on choroidal neovascularization: a quantitative and co-word analysis.

    Science.gov (United States)

    Zhao, Fangkun; Shi, Bei; Liu, Ruixin; Zhou, Wenkai; Shi, Dong; Zhang, Jinsong

    2018-04-03

    The distribution pattern and knowledge structure of choroidal neovascularization (CNV) was surveyed based on literatures in PubMed. Published scientific papers about CNV were retrieved from Jan 1st, 2012 to May 31st, 2017. Extracted MeSH terms were analyzed quantitatively by using Bibliographic Item Co-Occurrence Matrix Builder (BICOMB) and high-frequency MeSH terms were identified. Hierarchical cluster analysis was conducted by SPSS 19.0 according to the MeSH term-source article matrix. High-frequency MeSH terms co-occurrence matrix was constructed to support strategic diagram and social network analysis (SNA). According to the searching strategy, all together 2366 papers were included, and the number of annual papers changed slightly from Jan 1st, 2012 to May 31st, 2017. Among all the extracted MeSH terms, 44 high-frequency MeSH terms were identified and hotspots were clustered into 6 categories. In the strategic diagram, clinical drug therapy, pathology and diagnosis related researches of CNV were well developed. In contrast, the metabolism, etiology, complications, prevention and control of CNV in animal models, and genetics related researches of CNV were relatively immature, which offers potential research space for future study. As for the SNA result, the position status of each component was described by the centrality values. The studies on CNV are relatively divergent and the 6 research categories concluded from this study could reflect the publication trends on CNV to some extent. By providing a quantitative bibliometric research across a 5-year span, it could help to depict an overall command of the latest topics and provide some hints for researchers when launching new projects.

  19. Expression of hypoxia-inducible factor-1α and erythropoietin at corneal neovascularization in rats

    Directory of Open Access Journals (Sweden)

    Ji-Min Wang

    2014-12-01

    Full Text Available AIM: To describe the expression of hypoxia-inducible factor-1α(HIF-1αand erythropoietin(EPOin rats' corneal and evaluate its potential effect on corneal neovascularization(CNVgrowth. METHODS: The young SD rats(3mowas chosen and randomly divided into 2 groups, which were experimental group and normal control group. CNV model was established by alkali burn, and the length and area of CNV was observed everyday after operation by slit lamp. After that, the expression of HIF-1α and EPO was measured by SABC and RT-PCR methods at 1, 3, 5, 7, and 14d after alkali burn. The data was analyzed by SPSS 20.0. RESULTS: The area of CNV was increasing at 1, 3, 5, 7, and 14d after alkali burn, and the peak point appear at 7d. The growth speed was decreased after 14d. SABC method told us that no HIF-1α and very tiny amount EPO was detected at normal rats' corneal. The expression of the two factors increased at 1d after alkali burn in corneal epithelium and endoderm. The results of RT-PCR showed that a few amounts of HIF-1α and EPO mRNA were detected at normal group. The expression of the two factors was increased at 3d after alkali burn, and the peak value was found at 7d, however, it was decreased at 14d. Statistical difference was found at different time(PCONCLUSION: HIF-1α and EPO is closely related to CNV.

  20. OPTIMAL MANAGEMENT OF PIGMENT EPITHELIAL DETACHMENTS IN EYES WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

    Science.gov (United States)

    Khanani, Arshad M; Eichenbaum, David; Schlottmann, Patricio G; Tuomi, Lisa; Sarraf, David

    2018-04-24

    This review aimed to determine the optimal management of retinal pigment epithelial detachments (PEDs) in neovascular age-related macular degeneration (nAMD) based on review of available evidence in the literature. A comprehensive literature review evaluates previous retrospective and prospective studies that assessed the treatment of PEDs in nAMD. Studies illustrated that anti-vascular endothelial growth factor (VEGF) therapy can be effective in eyes with PED secondary to nAMD. Similar visual outcomes are associated with different anti-VEGF treatments. Higher anti-VEGF doses may improve anatomical response, without correlation with vision improvement. Fibrovascular PEDs may be difficult to treat, but even these eyes can gain vision with anti-VEGF therapy. A retinal pigment epithelial tear may develop in 15% to 20% of eyes with PEDs after anti-VEGF therapy, especially in PEDs greater than 500 µm to 600 µm in height; however, vision may stabilize with continued therapy. Atrophy may complicate eyes with PED and nAMD after anti-VEGF therapy, especially in association with complete PED resolution. Available literature suggests that anti-VEGF therapy is safe and efficacious for PED and nAMD. Treatment should focus on vision gains rather than PED resolution because there is no apparent correlation between anatomical and functional improvement in most eyes with PED and nAMD.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  1. Changes of subfoveal choroidal thickness after treated by Ranibizumab for choroidal neovascularization secondary to pathologic myopia

    Directory of Open Access Journals (Sweden)

    Jian-Shu Yuan

    2016-05-01

    Full Text Available AIM:To observe the change of subfoveal choroidal thickness(SFCTafter intravitreal injections of anti-vascular endothelial growth factor monoclonal antibody Ranibizumab in patients with choroidal neovascularization(CNVsecondary to pathologic myopia(PMand to research the relation between visual acuity and SFCT.METHODS:This was a prospective, contrast, open-label study.Fifty pathologic myopia patients with CNV(50 eyeswere recruited in this study. Before the injection,best-corrected visual acuity detected by visual chart from Early Treatment of Diabetic Retinopathy Study(ETDRS,non-contact tonometer,ophthalmoscope,fundus photography, fundus fluorescein angiograph(FFAand optical coherence tomography(OCTexamination were necessary. All affected eye were treated with intravitreal ranibizumab 0.05mL. Following up for 12mo, the changes of visual acuity and SFCT were compared before and after treatment, also the relation between them. RESULTS:All eyes received an average of 2.47±2.23 injections,the final vision of follow-up increased by 13.62±8.98 letters than that before(t=6.69,Pt=0.95, P>0.05.While after 6 and 12mo,the differences were significant(t=2.34, 2.61; PPP>0.05.There were no serious systemic or local side effects during the follow up.CONCLUSION:Intravitreal ranibizumab for CNV secondary to pathologic myopia is safe and can improve the visual acuity.Intravitreal injections of ranibizumab can induce SFCT reduction for CNV secondary to pathologic myopia.We hypothesized that increase of SFCT may be one of evaluation index for CNV activity.

  2. Intraocular Vascular Endothelial Growth Factor Levels in Pachychoroid Neovasculopathy and Neovascular Age-Related Macular Degeneration.

    Science.gov (United States)

    Hata, Masayuki; Yamashiro, Kenji; Ooto, Sotaro; Oishi, Akio; Tamura, Hiroshi; Miyata, Manabu; Ueda-Arakawa, Naoko; Takahashi, Ayako; Tsujikawa, Akitaka; Yoshimura, Nagahisa

    2017-01-01

    To investigate the difference in intraocular vascular endothelial growth factor (VEGF) concentration between pachychoroid neovasculopathy and neovascular age-related macular degeneration (nAMD) and its associations with responses to three monthly anti-VEGF injections as an initial treatment for the two conditions. This study included nine eyes with treatment-naïve pachychoroid neovasculopathy and 21 eyes with treatment-naïve nAMD. Before the initial intravitreal anti-VEGF injection, aqueous humor samples were collected and the concentration of VEGF was measured using enzyme-linked immunosorbent assay. The concentration was compared between the two conditions, and its associations with responses to anti-VEGF therapy were investigated. The mean VEGF concentration in pachychoroid neovasculopathy was significantly lower than that in nAMD (63.4 ± 17.8 pg/ml and 89.8 ± 45.0 pg/ml, respectively; P = 0.035). The VEGF concentration was associated with the presence or absence of drusen (β = 0.503, P = 0.004). After anti-VEGF therapy, 6 (66.7%) of 9 eyes with pachychoroid neovasculopathy and 17 (81.0%) of 21 eyes with nAMD achieved dry macula (P = 0.640). Dry macula at 3 months and 12 months was significantly associated with a low VEGF concentration in pachychoroid neovasculopathy (P = 0.013 and P = 0.042, respectively), but not in nAMD (P = 0.108 and P = 0.219). The mean VEGF concentration in pachychoroid neovasculopathy was lower than that in nAMD, suggesting that the way in which VEGF is involved in angiogenesis may differ between pachychoroid neovasculopathy and nAMD.

  3. The effect of intravitreal bevacizumab injection before Ahmed valve implantation in patients with neovascular glaucoma.

    Science.gov (United States)

    Kang, Jung Youb; Nam, Ki Yup; Lee, Sang Joon; Lee, Seung Uk

    2014-08-01

    To evaluate the effect of intravitreal bevacizumab (IVB) before Ahmed valve implantation for treatment of neovascular glaucoma (NVG). This study is a retrospective, comparative, consecutive case series. The study group consisted of 27 eyes of 26 patients with NVG who underwent an Ahmed valve implantation. Thirteen eyes were treated with Ahmed valve implantation alone (control group), and 14 eyes were treated with a combination of preoperative IVB injection and Ahmed valve implantation (IVB group). Visual acuity, intraocular pressure (IOP), number of anti-glaucoma medications, surgical complications, and success rate were compared between the two groups. There were no significant differences in preoperative characteristics between the two groups. Visual acuity at 1, 2 weeks, and 1 month after surgery were significantly better in the IVB group (p = 0.038, 0.034, and 0.032, respectively). Hyphema associated with Ahmed valve implantation occurred significantly less in the IVB group (p = 0.016). On the other hand, the mean IOP and number of anti-glaucoma medications at all follow-up periods were similar between the two groups. Kaplan-Meier survival analysis showed the probability of success 6 months after surgery as 71.4 % in the IVB group and 84.6 % in the control group. No significant difference in success rate was found between the groups (p = 0.422). IVB before Ahmed valve implantation for treatment of NVG reduced the incidence of hyphema. In this retrospective study, IVB provided better visual outcome in the early postoperative periods but did not significantly improve mean IOP, number of anti-glaucoma medications, or success rate.

  4. Clinical efficacy analysis of Ahmed glaucoma valve implantation in neovascular glaucoma and influencing factors

    Science.gov (United States)

    He, Ye; Tian, Ying; Song, Weitao; Su, Ting; Jiang, Haibo; Xia, Xiaobo

    2017-01-01

    Abstract This study aimed to evaluate the efficacy of Ahmed glaucoma valve (AGV) implantation in treating neovascular glaucoma (NVG) and to analyze the factors influencing the surgical success rate. This is a retrospective review of 40 eyes of 40 NVG patients who underwent AGV implantation at Xiangya Hospital of Central South University, China, between January 2014 and December 2016. Pre- and postoperative intraocular pressure (IOP), visual acuity, surgical success rate, medications, and complications were observed. Surgical success criteria were defined as IOP ≤21 and >6 mm Hg with or without additional medications. Kaplan–Meier survival curves and Multivariate cox regression analysis were used to examine success rates and risk factors for surgical outcomes. The mean follow-up period was 8.88 ± 3.12 months (range: 3–17). IOP declined at each visit postoperatively and it was statistically significant (P < .001). An average of 3.55 ± 0.86 drugs was applied preoperatively, while an average of 0.64 ± 0.90 drugs was used postoperatively, with the difference being of statistical significance (P < .05). The complete surgical success rate of 3, 6, and 12 months after the operation was 85%, 75%, and 65%, respectively. Meanwhile, the qualified success rate of 3, 6, and 12 months after the operation was 85%, 80%, and 77.5%, respectively. The multivariate cox regression analysis showed that age (hazard ratio: 3.717, 7.246; 95% confidence interval: 1.149–12.048, 1.349–38.461; P = .028, .021) was influencing factors for complete success rate and qualified success rate among all NVG patients. Gender, previous operation history, primary disease, and preoperative IOP were found to be not significant. AGV implantation is an effective and safe surgical method to treat NVG. Age is an important factor influencing the surgical success rate. PMID:29049253

  5. Patchy Chorioretinal Atrophy Changes at the Posterior Pole After Ranibizumab for Myopic Choroidal Neovascularization.

    Science.gov (United States)

    Parravano, Mariacristina; Scarinci, Fabio; Gilardi, Marta; Querques, Lea; Varano, Monica; Oddone, Francesco; Bandello, Francesco; Querques, Giuseppe

    2017-12-01

    To investigate the potential role of ranibizumab treatment on the development or enlargement of chorioretinal atrophy (CRA) at the posterior pole in eyes with myopic choroidal neovascularization (mCNV). This observational case series included patients having high myopia spherical equivalent refractive error ≥ -6.00 diopters, axial length (AxL) ≥ 26.0 mm in both eyes, and mCNV treated with ranibizumab 0.5 mg in one eye, who were retrospectively enrolled. Areas of CRA in treated and fellow eyes were measured on fundus autofluorescence images at baseline, 12, and 24 months. The CRA hypoautofluorescent lesions were divided in two groups: perilesional atrophy, corresponding to area around the mCNV, and patchy extralesional atrophy, corresponding to CRA between the temporal vascular arcades. Thirty-six eyes of 18 patients were included. The mean perilesional CRA size significantly increased from baseline to 12 months (3.5 ± 10.6 mm2, P = 0.02) and 24 months (4.4 ± 11.7 mm2, P = 0.038) in the treated eye. In treated and not treated eyes, patchy extralesional CRA at the posterior pole increased significantly from baseline to 12 and 24 months follow-up. None of the fellow eyes developed mCNV. No significant relationship was found between the number of injections, AxL, age, and perilesional and patchy extralesional CRA in the treated and not treated eyes (P > 0.05). In eyes with pathologic myopia and mCNV, intravitreal injections of ranibizumab should not be considered as a contributing risk factor worsening the natural course of CRA, even though the risk of the perilesional CRA enlargement should be taken into account.

  6. En-face optical coherence tomography angiography of neovascularization elsewhere in hemicentral retinal vein occlusion

    Directory of Open Access Journals (Sweden)

    Sogawa K

    2015-10-01

    Full Text Available Kenji Sogawa, Taiji Nagaoka, Akihiro Ishibazawa, Atsushi Takahashi, Tomofumi Tani, Akitoshi Yoshida Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan Purpose: To evaluate how the growth of neovascularization elsewhere (NVE was delineated in an eye with hemicentral retinal vein occlusion (CRVO using optical coherence tomography (OCT angiography. Patients and methods: We examined a 64-year-old man diagnosed with hemi-CRVO. The area around the occluded vein was scanned using a spectral-domain OCT device (RTVue XR Avanti. Blood flow was detected using the split-spectrum amplitude-decorrelation angiography (SSADA algorithm. Color fundus photography, fluorescein angiography (FA, and OCT angiography examinations were performed at the first visit and at 3 and 6 months postpresentation. Results: At the first visit, FA revealed delayed retinal venous filling and extensive areas of capillary nonperfusion. The patient underwent a trial of intravitreal ranibizumab injection (0.5 mg/0.05 mL for the treatment of macular edema. At 3 months postpresentation, there was no NVE around the occluded vein in the en-face SSADA image, but at 6 months, NVE appeared on the occluded veins. The en-face SSADA image showed the NVE structure in the fibrovascular membrane on the occluded vein more clearly than FA images. Conclusion: OCT angiography clearly visualized the sprouting of NVE in an eye with hemi-CRVO. New findings of the vascular structure of NVE in hemi-CRVO were revealed using the en-face SSADA algorithm. Keywords: OCT angiography, hemi-CRVO, NVE

  7. Imaging choroidal neovascular membrane using en face swept-source optical coherence tomography angiography

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    Moussa M

    2017-10-01

    Full Text Available Magdy Moussa,1,2 Mahmoud Leila,3 Hagar Khalid1,2 1Ophthalmology Department, Faculty of Medicine, Tanta University, Tanta, Egypt; 2MEDIC Eye Center, Tanta, Egypt; 3Retina Department, Research Institute of Ophthalmology, Giza, Egypt Purpose: The aim of this study was to assess the efficacy of swept-source optical coherence tomography angiography (SS-OCTA in delineating the morphology of choroidal neovascular membrane (CNV. Patients and methods: This was a retrospective observational case series reviewing clinical data and fundus fluorescein angiography (FFA, swept-source optical coherence tomography (SS-OCT, and SS-OCTA images of patients with CNV and comparing the findings. The swept-source technology enables deeper penetration and superior axial resolution. The incorporated blood flow detection algorithm, optical coherence tomography angiography ratio analysis (OCTARA, enables visualization of CNV in vivo without the need for dye injection. Results: The study included 136 eyes of 105 patients. Active lesions on SS-OCTA images showed increased capillary density, extensive arborization, vascular anastomosis and looping, and peri-lesional hollow. Inactive lesions showed decreased capillary density, presence of large linear vessels, and presence of feeder vessels supplying the CNV. We detected positive correlation between SS-OCTA, FFA, and SS-OCT images in 97% of eyes. In the remaining 3%, SS-OCTA confirmed the absence of CNV, whereas FFA and SS-OCT either were inconclusive in the diagnosis of CNV or yielded false-positive results. Conclusion: SS-OCT and SS-OCTA represent a reproducible risk-free analog for FFA in imaging CNV. SS-OCTA is particularly versatile in cases where FFA and SS-OCT are inconclusive. Keywords: swept-source OCT, OCT angiography, imaging of CNV, OCTARA algorithm

  8. Mathematical modeling of atherosclerotic plaque destabilization: Role of neovascularization and intraplaque hemorrhage.

    Science.gov (United States)

    Guo, Muyi; Cai, Yan; Yao, Xinke; Li, Zhiyong

    2018-08-07

    Observational studies have identified angiogenesis from the adventitial vasa vasorum and intraplaque hemorrhage (IPH) as critical factors in atherosclerotic plaque progression and destabilization. Here we propose a mathematical model incorporating intraplaque neovascularization and hemodynamic calculation with plaque destabilization for the quantitative evaluation of the role of neoangiogenesis and IPH in the vulnerable atherosclerotic plaque formation. An angiogenic microvasculature is generated by two-dimensional nine-point discretization of endothelial cell proliferation and migration from the vasa vasorum. Three key cells (endothelial cells, smooth muscle cells and macrophages) and three key chemicals (vascular endothelial growth factors, extracellular matrix and matrix metalloproteinase) are involved in the plaque progression model, and described by the reaction-diffusion partial differential equations. The hemodynamic calculation of the microcirculation on the generated microvessel network is carried out by coupling the intravascular, interstitial and transvascular flow. The plasma concentration in the interstitial domain is defined as the description of IPH area according to the diffusion and convection with the interstitial fluid flow, as well as the extravascular movement across the leaky vessel wall. The simulation results demonstrate a series of pathophysiological phenomena during the vulnerable progression of an atherosclerotic plaque, including the expanding necrotic core, the exacerbated inflammation, the high microvessel density (MVD) region at the shoulder areas, the transvascular flow through the capillary wall and the IPH. The important role of IPH in the plaque destabilization is evidenced by simulations with varied model parameters. It is found that the IPH can significantly speed up the plaque vulnerability by increasing necrotic core and thinning fibrous cap. In addition, the decreased MVD and vessel permeability may slow down the process of

  9. A Pharmacodynamic Analysis of Choroidal Neovascularization in a Porcine Model Using Three Targeted Drugs

    Science.gov (United States)

    Tran, Jeffrey; Craven, Caroline; Wabner, Kathy; Schmit, Jenn; Matter, Brock; Kompella, Uday; Grossniklaus, Hans E.; Olsen, Timothy W.

    2017-01-01

    Purpose To compare the efficacy of microneedle-delivered suprachoroidal (SC) pazopanib to intravitreal (Ivit) delivery of pazopanib, bevacizumab, or a fusion protein hI-con1 versus vehicle controls on choroidal neovascularization (CNV) growth in a pig model. Methods Forty-one pigs were injected on the day of CNV induction (hI-con1 on postinduction day 14) with either 2.5 mg Ivit bevacizumab (n = 9), 1 mg Ivit pazopanib (n = 9), 300 Ivit μg hI-con1 (n = 4), or 1 mg SC pazopanib (n = 9), vs. 10 vehicle controls (3 SC + 7 Ivit = 10). Pigs were euthanized at week 2 (11), 3 (8), 4 (11), and 8 (11), and eyes were fixed for histology. The size of the CNV was determined from histology, and CNV height was the primary outcome measure. Immunostaining for cytotoxic T-cells was performed in the hI-con1 study. Results In 39 of 41 (95%) eyes, type 2 CNV lesions were identified. One CNV lesion was lost during dissection. One animal was euthanized due to surgical complications. For mean CNV size comparisons, Ivit pazopanib had smaller mean height measurements (90 ± 20 μm) versus controls (180 ± 20 μm; P = 0.009), and Ivit pazopanib had smaller maximum CNV height (173 ± 43 μm) compared to SC pazopanib (478 ± 105 μm; P = 0.018). The mean lesion size in hI-con1–treated animals trended smaller than in controls (P = 0.11). Immunostaining did not detect cytotoxic T-cells. Conclusions Intravitreal pazopanib and to a lesser extent hI-con1 reduced the size of CNV lesions. The pig model has nearly a 100% rate of type 2 CNV induction and is a reliable preclinical model with pharmacodynamics similar to humans. PMID:28738417

  10. RETINAL PIGMENT EPITHELIAL TEAR AFTER INTRAVITREAL RANIBIZUMAB TREATMENT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

    Science.gov (United States)

    Cho, Han Joo; Kim, Hyoung Seok; Yoo, Seul Gi; Han, Jung Il; Lew, Young Ju; Cho, Sung Won; Lee, Tae Gon; Kim, Jong Woo

    2016-10-01

    To evaluate the risk factors for retinal pigment epithelium (RPE) tears after intravitreal ranibizumab injections in neovascular age-related macular degeneration (nAMD) and to determine the efficacy of continued ranibizumab treatment after RPE tears. A total of 407 treatment-naïve eyes (377 patients) with nAMD were retrospectively included. All patients were treated with an initial series of 3 monthly loading injections, followed by further injections as required. Baseline characteristics and pigment epithelial detachment (PED) lesion features were evaluated as potential risk factors for RPE tear. The visual and anatomical outcomes after treatment during 12 months were also evaluated. By 12 months, RPE tears developed in 32 eyes (7.9%). Pigment epithelial detachment height was associated with a higher risk of RPE tear (odds ratio [OR], 1.318; 95% confidence interval [CI], 1.217-2.031, P = 0.018). Fibrovascular PED compared with serous PED had a higher risk of developing tears (OR, 9.129; 95% CI, 6.228-32.124, P = 0.039), and typical nAMD (OR, 4.166; 95% CI, 2.030-14.913, P = 0.031) and retinal angiomatous proliferation (OR, 3.778; 95% CI, 2.185-9.277, P = 0.040) had a higher risk of developing tears compared with polypoidal choroidal vasculopathy. Mean best-corrected visual acuity (BCVA) of RPE tear patients showed no significant improvement after treatment at 12 months; however, patients with RPE tears without foveal involvement (19 eyes) showed significant BCVA improvement at 12 months (P = 0.034). PED type and nAMD subtype are associated with the development of RPE tears after intravitreal ranibizumab injections. Continued ranibizumab therapy after RPE tear development can maintain visual acuity when the fovea is not involved.

  11. Bevacizumab vs ranibizumab for neovascular age-related macular degeneration in Chinese patients

    Directory of Open Access Journals (Sweden)

    Zhe-Li Liu

    2013-04-01

    Full Text Available AIM:To compare the clinical efficacy of intravitreal injections of bevacizumab and ranibizumab for treating Chinese patients with neovascular age-related macular degeneration (AMD. METHODS: Among 60 Chinese patients with exudative AMD (60 eyes, 28 received intravitreal bevacizumab injections (1.25mg and 32 received intravitreal ranibizumab injections (0.5mg, once a month for 3 months and were followed for a total of 6 months. Monthly optical coherence tomography (OCT was used to determine whether the patients received additional treatments during the follow-up. We compared the baseline and 6-month follow-up values of mean best-corrected visual acuity (BCVA and central retinal thickness (CRT in both groups of patients. We also compared the occurrence of adverse events. RESULTS:At the 6-month follow-up, the mean BCVA (logMAR of the bevacizumab and ranibizumab treatment groups improved from the baseline measurements of 0.72±0.23 and 0.73±0.22 to 0.47±0.14 and 0.45±0.20, respectively (P<0.05 for both groups. However, the change was not significantly different between the two groups. As evaluated by OCT, CRT decreased from 366.71±34.72μm and 352±36.9μm at baseline to 250.86±41.51μm and 243.22±41.38μm in the bevacizumab and ranibizumab groups, respectively (P<0.05 for both groups. However, the change was not significantly different between the two groups. There were no severe local adverse reactions or systemic adverse events. CONCLUSION:Intravitreal bevacizumab and ranibizumab have equivalent effects on BCVA and CRT and appeare safe over the short-term.

  12. Neovascular Glaucoma After Stereotactic Radiotherapy for Juxtapapillary Choroidal Melanoma: Histopathologic and Dosimetric Findings

    International Nuclear Information System (INIS)

    Fernandes, Bruno F.; Weisbrod, Daniel; Yuecel, Yeni H.; Follwell, Matthew; Krema, Hatem; Heydarian, Mostafa; Xu Wei; Payne, David; McGowan, Hugh; Simpson, Ernest R.; Laperriere, Normand; Sahgal, Arjun

    2011-01-01

    Purpose: Enucleation after stereotactic radiotherapy (SRT) for juxtapapillary choroidal melanoma may be required because of tumor progression (TP) or the development of intractable radiation-induced neovascular glaucoma (NVG). We compare pathologic changes and dosimetric findings in those eyes enucleated secondary to NVG as opposed to TP to better understand potential mechanisms. Methods and Materials: Patients with juxtapapillary choroidal melanoma treated with SRT (70 Gy in 5 fractions, alternate days over a total of 10 days) at the Princess Margaret Hospital, Toronto, Ontario, Canada, who underwent enucleation between 1998 and 2006 were selected. We correlated dosimetric data based on the patient's original SRT treatment plan with histopathologic findings in the retina, optic nerve head, and anterior chamber. A dedicated ocular pathologist reviewed each case in a blinded fashion. Results: Ten eyes in ten patients were enucleated after SRT. Six were enucleated secondary to NVG and four secondary to because of TP. Aggressive tumor features such as invasion of the sclera and epithelioid cell type were observed predominantly in the TP group. Retinal damage was more predominant in the NVG group, as were findings of radiation-related retinal vascular changes of fibrinoid necrosis and hyalinization. No conclusive radiation-related effects were found in the anterior chamber. The maximum point dose and dose to 0.1 cc were lower for the anterior chamber as compared with the dose to the tumor, retina, and optic nerve head. The mean 0.1-cc doses to the retina were 69.4 Gy and 73.5 Gy and to the anterior chamber were 4.9 Gy and 17.3 Gy for the NVG group and tumor progression group, respectively. Conclusions: Our findings suggest that NVG is due to radiation damage to the posterior chamber of the eye rather than primary radiation damage to the anterior segment.

  13. Targeted decorin gene therapy delivered with adeno-associated virus effectively retards corneal neovascularization in vivo.

    Directory of Open Access Journals (Sweden)

    Rajiv R Mohan

    Full Text Available Decorin, small leucine-rich proteoglycan, has been shown to modulate angiogenesis in nonocular tissues. This study tested a hypothesis that tissue-selective targeted decorin gene therapy delivered to the rabbit stroma with adeno-associated virus serotype 5 (AAV5 impedes corneal neovascularization (CNV in vivo without significant side effects. An established rabbit CNV model was used. Targeted decorin gene therapy in the rabbit stroma was delivered with a single topical AAV5 titer (100 µl; 5×10(12 vg/ml application onto the stroma for two minutes after removing corneal epithelium. The levels of CNV were examined with stereomicroscopy, H&E staining, lectin, collagen type IV, CD31 immunocytochemistry and CD31 immunoblotting. Real-time PCR quantified mRNA expression of pro- and anti-angiogenic genes. Corneal health in live animals was monitored with clinical, slit-lamp and optical coherence tomography biomicroscopic examinations. Selective decorin delivery into stroma showed significant 52% (p<0.05, 66% (p<0.001, and 63% (p<0.01 reduction at early (day 5, mid (day 10, and late (day 14 stages of CNV in decorin-delivered rabbit corneas compared to control (no decorin delivered corneas in morphometric analysis. The H&E staining, lectin, collagen type IV, CD31 immunostaining (57-65, p<0.5, and CD31 immunoblotting (62-67%, p<0.05 supported morphometric findings. Quantitative PCR studies demonstrated decorin gene therapy down-regulated expression of VEGF, MCP1 and angiopoietin (pro-angiogenic and up-regulated PEDF (anti-angiogenic genes. The clinical, biomicroscopy and transmission electron microscopy studies revealed that AAV5-mediated decorin gene therapy is safe for the cornea. Tissue-targeted AAV5-mediated decorin gene therapy decreases CNV with no major side effects, and could potentially be used for treating patients.

  14. Emerging vascular endothelial growth factor antagonists to treat neovascular age-related macular degeneration.

    Science.gov (United States)

    Hussain, Rehan M; Ciulla, Thomas A

    2017-09-01

    Evolving anti-vascular endothelial growth factor (VEGF) treatments for neovascular age-related macular degeneration (nAMD) include long acting agents, combination strategies involving new pathways, topical agents, sustained-release, and genetic therapy strategies. Areas covered: Brolucizumab and abicipar pegol have smaller molecular size, facilitating higher concentrations and potentially longer duration than current anti-VEGF agents. Agents being combined with anti-VEGFs include OPT-302 (to inhibit VEGF-C and VEGF-D); pegpleranib and rinucumab (to inhibit platelet derived growth factor, PDGF - but both failed to show consistently improved visual outcomes compared to anti-VEGF monotherapy); and RG7716, ARP-1536 and nesvacumab (to activate the Tie-2 tyrosine kinase receptor, which reduces permeability). X-82 is an oral anti-VEGF and anti-PDGF being tested in phase 2 studies. Topical anti-VEGF ± anti-PDGF drugs under study include pazopanib, PAN-90806, squalamine lactate, regorafinib, and LHA510. Sustained-release anti-VEGF delivery treatments, such as the ranibizumab Port Delivery System, GB-102, NT-503, hydrogel depot, Durasert, and ENV1305 aim to reduce the burden of frequent injections. Gene therapies with new viral vectors hold the potential to induce sustained expression of anti-angiogenic proteins via the retina's cellular apparatus, and include AVA-101/201, ADVM-202/302, AAV2-sFLT01, RGX314, and Retinostat. Expert opinion: There are many emerging anti-VEGF treatments that aim to improve visual outcomes and reduce the treatment burden of nAMD.

  15. Pegaptanib: choroidal neovascularization in patients with age-related macular degeneration and previous arterial thromboembolic events.

    Science.gov (United States)

    Battaglia Parodi, Maurizio; Di Bartolo, Emanuele; Brue, Claudia; Cappello, Ezio; Furino, Claudio; Giuffrida, Sebastiano; Imparato, Manuela; Reibaldi, Michele

    2018-01-01

    To evaluate the efficacy and the rate of side effects of the pegylated aptamer pegaptanib in the treatment of patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) and a history of previous arterial thromboembolic events (ATEs). Twenty-three eyes of 23 patients with subfoveal CNV due to AMD and cerebrovascular accidents (n = 12) and myocardial infarction (n = 11) in the previous 6 months received intravitreal pegaptanib 0.3 mg according to a pro re nata regimen and were followed for 12 months. The paired Student t test was used to evaluate mean changes in best-corrected visual acuity (BCVA; primary outcome measure) and central foveal thickness (CFT). The mean patient age was 71.5 ± 4.6 years; there were 14 women and 9 men. The CNV was type 1, 2, and 3 in 18, 3, and 2 eyes, respectively. The mean BCVA improved from 0.67 ± 0.23 logMAR at baseline to 0.52 ± 0.31 logMAR at the end of 12-month follow-up (p = 0.044). Thirty-five percent of patients achieved ≥3 Early Treatment Diabetic Retinopathy Study lines improvement at 12 months. Mean CFT at baseline (381 ± 111 µm) decreased to 304 ± 82 µm at 12 months (p = 0.008). Patients received a mean of 4.3 ± 1.3 (range 3-7) injections. No systemic or ocular side effects occurred; no patient experienced further ATEs. Intravitreal pegaptanib can be considered a viable treatment option for patients with AMD-related CNV who are at high risk of ATEs.

  16. Risks of newly onset hemorrhagic stroke in patients with neovascular age-related macular degeneration.

    Science.gov (United States)

    Lee, Wan-Ju Annabelle; Cheng, Ching-Lan; Lee, Cheng-Han; Kao Yang, Yea-Huei; Lin, Swu-Jane; Hsieh, Cheng-Yang

    2017-10-01

    Age-related macular degeneration (AMD) is an eye disease causing blindness in the elderly. It shares many common possible pathogenic mechanisms with cardiovascular diseases. Many studies have discussed the association between AMD and stroke, but the results were inconsistent. Our aim was to determine the associations between neovascular AMD and the risk of stroke in the Taiwanese population. This is a retrospective cohort study. We used claims data from National Health Insurance Research Database. Patients aged more than 45 years without stroke, myocardial infarction, or any AMD were selected from 2001 to 2008 and followed until 2010. The index date was defined as the date of nAMD diagnosis (ICD-9 code, 362.52). The comparison group was patients without an nAMD diagnosis with age- and sex-matched to nAMD subjects at a ratio of up to 10 to 1. Kaplan-Meier survival analysis and Cox regression analysis were used. The incidence of stroke events (ICD-9 codes, 430-434) and their subtypes (hemorrhagic and ischemic) were primary outcomes. Secondary outcomes included acute myocardial infarction (AMI), composite AMI/stroke, and all-cause mortality. Patients with nAMD had a higher risk of developing stroke, with an adjusted HR of 1.30 (95% CI, 1.01-1.68). A higher risk for hemorrhagic stroke (HR, 1.70, 95% CI, 1.03-2.83) was also found. No significant differences were observed in ischemic stroke, the composite of AMI/stroke, and all-cause mortality. Patients with nAMD had a significantly higher risk of developing stroke, which was driven mainly by the increased risk of developing the hemorrhagic subtype. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Nitric oxide and calcium ions in apoptotic esophageal carcinoma cells induced by arsenite

    Science.gov (United States)

    Shen, Zhong-Ying; Shen, Wen-Ying; Chen, Ming-Hua; Shen, Jian; Cai, Wei-Jie; Yi, Zeng

    2002-01-01

    AIM: To Quantitatively analyze the nitri oxide (NO) and Ca2+ in apoptosis of esophageal carcinoma cells induced by arsenic trioxide (As2O3). METHODS: The cell line SHEEC1, a malignant esophageal epithelial cell induced by HPV in synergy with TPA in our laboratory, was cultured in a serum-free medium and treated with As2O3. Before and after administration of As2O3, NO production in cultured medium was detected quantitatively using the Griess Colorimetric method. Intracellular Ca2+ was labeled by using the fluorescent dye Fluo3-AM and detected under confocal laser scanning microscope (CLSM), which was able to acquire data in real-time enabling Ca2+ dynamics of individual cells in vitro. The apoptotic cells were examined under electron microscopy. RESULTS: Intracellular concentration of Ca2+ increased from 1.00 units to 1.09-1.38 units of fluorescent intensity at As2O3 treatment and NO products subsequently released from As2O3-treated cells increased from 0.98-1.00 × 10-2 μmol·L-1 up to 1.48-1.52 × 10-2 μmol·L-1 and maintained in a high level continuously. Finally apoptosis of cells occurred, chromatin being agglutinated, cells shrunk, nuclei became round and mitochondria swelled. CONCLUSION: Ca2+ and NO increased with cell damage and apoptosis in cells treated by As2O3. The Ca2+ is an initial messenger to the apoptotic pathway. To investigate Ca2+ and NO will be a new direction for studying the apoptotic signaling messenger of the esophageal carcinoma cells induced by As2O3. PMID:11833068

  18. α-Ketoglutarate Promotes Pancreatic Progenitor-Like Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Jing Song

    2018-03-01

    Full Text Available A major source of β cell generation is pancreatic progenitor-like cell differentiation. Multiple studies have confirmed that stem cell metabolism plays important roles in self-renewal and proliferation. In the absence of glucose, glutamine provides the energy for cell division and growth. Furthermore, α-ketoglutarate (αKG, a precursor for glutamine synthesis, is sufficient for enabling glutamine-independent cell proliferation. We have demonstrated that αKG contributes to the large-scale proliferation of pancreatic progenitor-like cells that can provide an ample amount of clinically relevant β cells. We compared the mRNA expression of a subset of genes, the abundance of ATP, reactive oxide species, mitochondrial number, and the colony-forming frequency between mouse pancreatic CD133+ and CD133− cells. We employed Real-Time PCR, immunostaining and passage assays to investigate self-renewal and proliferation of pancreatic progenitor-like cells in a 3D culture system in the presence and absence of αKG. The energy metabolism of CD133+ cells was more prone to oxidative phosphorylation. However, in the 3D culture system, when αKG was supplemented to the culture medium, the proliferation of the pancreatic progenitor-like cells was significantly elevated. We confirmed that the presence of αKG correlated with the up-regulation of Ten-Eleven Translocation (Tet. αKG can promote the proliferation of pancreatic progenitor-like cells via the up-regulation of Tet.

  19. α-Ketoglutarate Promotes Pancreatic Progenitor-Like Cell Proliferation.

    Science.gov (United States)

    Song, Jing; Ma, Dongshen; Xing, Yun; Tang, Shanshan; Alahdal, Murad; Guo, Jiamin; Pan, Yi; Zhang, Yanfeng; Shen, Yumeng; Wu, Qiong; Lu, Zhou; Jin, Liang

    2018-03-22

    A major source of β cell generation is pancreatic progenitor-like cell differentiation. Multiple studies have confirmed that stem cell metabolism plays important roles in self-renewal and proliferation. In the absence of glucose, glutamine provides the energy for cell division and growth. Furthermore, α-ketoglutarate (αKG), a precursor for glutamine synthesis, is sufficient for enabling glutamine-independent cell proliferation. We have demonstrated that αKG contributes to the large-scale proliferation of pancreatic progenitor-like cells that can provide an ample amount of clinically relevant β cells. We compared the mRNA expression of a subset of genes, the abundance of ATP, reactive oxide species, mitochondrial number, and the colony-forming frequency between mouse pancreatic CD133⁺ and CD133 - cells. We employed Real-Time PCR, immunostaining and passage assays to investigate self-renewal and proliferation of pancreatic progenitor-like cells in a 3D culture system in the presence and absence of αKG. The energy metabolism of CD133⁺ cells was more prone to oxidative phosphorylation. However, in the 3D culture system, when αKG was supplemented to the culture medium, the proliferation of the pancreatic progenitor-like cells was significantly elevated. We confirmed that the presence of αKG correlated with the up-regulation of Ten-Eleven Translocation (Tet). αKG can promote the proliferation of pancreatic progenitor-like cells via the up-regulation of Tet.

  20. [Stem and progenitor cells in biostructure of blood vessel walls].

    Science.gov (United States)

    Korta, Krzysztof; Kupczyk, Piotr; Skóra, Jan; Pupka, Artur; Zejler, Paweł; Hołysz, Marcin; Gajda, Mariusz; Nowakowska, Beata; Barć, Piotr; Dorobisz, Andrzej T; Dawiskiba, Tomasz; Szyber, Piotr; Bar, Julia

    2013-09-18

    Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, "anchored" in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC). Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as "subendothelial or vasculogenic zones". Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

  1. Stem and progenitor cells in biostructure of blood vessel walls

    Directory of Open Access Journals (Sweden)

    Krzysztof Korta

    2013-09-01

    Full Text Available Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, “anchored” in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC. Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as “subendothelial or vasculogenic zones”. Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

  2. Functional impact of treatment with ranibizumab under a reactive strategy in patients with neovascular age-related macular degeneration.

    Science.gov (United States)

    Gallego-Pinazo, R; Dolz-Marco, R; Andreu-Fenoll, M; Farrés, J; Monclús, L

    2017-03-01

    To analyse the functional recovery using a pro re nata (PRN) dosing strategy with intravitreal injections of ranibizumab for patients with neovascular age-related macular degeneration (AMD). An observational, retrospective, single-centre study, was conducted on patients with neovascular AMD managed with a PRN strategy with ranibizumab, and were followed-up for a minimum of 18 months. Sociodemographic and clinical data were collected from medical records. The percentage of visual acuity (VA) recovered after losing 5 or more letters was calculated taking into account the previous visit, as well as considering the best VA recorded prior to the retreament. The analysis included 128 patients. The mean (SD) follow-up period was 18.9 (2.3) months. The mean (SD) elapsed days between onset of symptoms and diagnosis, and between prescription and administration of treatment was 50.2 (57.4) and 10.9 (16.0), respectively. Only 108 patients were prescribed ranibizumab after losing 5 or more letters of VA. The mean (SD) VA recovery compared to the previous VA was 70.3% (114.4). On the other hand, the mean (SD) VA recovery when considering the best VA registered before the retreatment was 43.5% (112.9), with 59.4% of re-treatments having a VA recovery below 75%, and with 11.7% not presenting any VA recovery. A PRN dosing strategy with intravitreal ranibizumab for neovascular AMD may not be efficient in preserving and/or recovering VA in the long-term, due to a cumulative irreversible VA loss. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA).

    Science.gov (United States)

    Schmidt-Erfurth, Ursula; Chong, Victor; Loewenstein, Anat; Larsen, Michael; Souied, Eric; Schlingemann, Reinier; Eldem, Bora; Monés, Jordi; Richard, Gisbert; Bandello, Francesco

    2014-09-01

    Age-related macular degeneration (AMD) is still referred to as the leading cause of severe and irreversible visual loss world-wide. The disease has a profound effect on quality of life of affected individuals and represents a major socioeconomic challenge for societies due to the exponential increase in life expectancy and environmental risks. Advances in medical research have identified vascular endothelial growth factor (VEGF) as an important pathophysiological player in neovascular AMD and intraocular inhibition of VEGF as one of the most efficient therapies in medicine. The wide introduction of anti-VEGF therapy has led to an overwhelming improvement in the prognosis of patients affected by neovascular AMD, allowing recovery and maintenance of visual function in the vast majority of patients. However, the therapeutic benefit is accompanied by significant economic investments, unresolved medicolegal debates about the use of off-label substances and overwhelming problems in large population management. The burden of disease has turned into a burden of care with a dissociation of scientific advances and real-world clinical performance. Simultaneously, ground-breaking innovations in diagnostic technologies, such as optical coherence tomography, allows unprecedented high-resolution visualisation of disease morphology and provides a promising horizon for early disease detection and efficient therapeutic follow-up. However, definite conclusions from morphologic parameters are still lacking, and valid biomarkers have yet to be identified to provide a practical base for disease management. The European Society of Retina Specialists offers expert guidance for diagnostic and therapeutic management of neovascular AMD supporting healthcare givers and doctors in providing the best state-of-the-art care to their patients. NCT01318941. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  4. Density-tunable conjugation of cyclic RGD ligands with polyion complex vesicles for the neovascular imaging of orthotopic glioblastomas

    International Nuclear Information System (INIS)

    Kawamura, Wataru; Nomoto, Takahiro; Sueyoshi, Daiki; Kataoka, Kazunori; Miura, Yutaka; Toh, Kazuko; Yamada, Naoki; Matsumoto, Yu; Liu, Xueying; Kokuryo, Daisuke; Aoki, Ichio; Saga, Tsuneo; Kano, Mitsunobu R; Nishiyama, Nobuhiro; Kishimura, Akihiro

    2015-01-01

    Introduction of ligands into 100 nm scaled hollow capsules has great potential for diagnostic and therapeutic applications in drug delivery systems. Polyethylene glycol-conjugated (PEGylated) polyion complex vesicles (PICsomes) are promising hollow nano-capsules that can survive for long periods in the blood circulation and can be used to deliver water-soluble macromolecules to target tissues. In this study, cyclic RGD (cRGD) peptide, which is specifically recognized by α V β 3 and α v β 5 integrins that are expressed at high levels in the neovascular system, was conjugated onto the distal end of PEG strands on PICsomes for active neovascular targeting. Density-tunable cRGD-conjugation was achieved using PICsomes with definite fraction of end-functionalized PEG, to substitute 20, 40, and 100% of PEG distal end of the PICsomes to cRGD moieties. Compared with control-PICsomes without cRGD, cRGD-PICsomes exhibited increased uptake into human umbilical vein endothelial cells. Intravital confocal laser scanning microscopy revealed that the 40%-cRGD-PICsomes accumulated mainly in the tumor neovasculature and remained in the perivascular region even after 24 h. Furthermore, we prepared superparamagnetic iron oxide (SPIO)-loaded cRGD-PICsomes for magnetic resonance imaging (MRI) and successfully visualized the neovasculature in an orthotopic glioblastoma model, which suggests that SPIO-loaded cRGD-PICsomes might be useful as a MRI contrast reagent for imaging of the tumor microenvironment, including neovascular regions that overexpress α V β 3 integrins. (paper)

  5. Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA)

    Science.gov (United States)

    Schmidt-Erfurth, Ursula; Chong, Victor; Loewenstein, Anat; Larsen, Michael; Souied, Eric; Schlingemann, Reinier; Eldem, Bora; Monés, Jordi; Richard, Gisbert; Bandello, Francesco

    2014-01-01

    Age-related macular degeneration (AMD) is still referred to as the leading cause of severe and irreversible visual loss world-wide. The disease has a profound effect on quality of life of affected individuals and represents a major socioeconomic challenge for societies due to the exponential increase in life expectancy and environmental risks. Advances in medical research have identified vascular endothelial growth factor (VEGF) as an important pathophysiological player in neovascular AMD and intraocular inhibition of VEGF as one of the most efficient therapies in medicine. The wide introduction of anti-VEGF therapy has led to an overwhelming improvement in the prognosis of patients affected by neovascular AMD, allowing recovery and maintenance of visual function in the vast majority of patients. However, the therapeutic benefit is accompanied by significant economic investments, unresolved medicolegal debates about the use of off-label substances and overwhelming problems in large population management. The burden of disease has turned into a burden of care with a dissociation of scientific advances and real-world clinical performance. Simultaneously, ground-breaking innovations in diagnostic technologies, such as optical coherence tomography, allows unprecedented high-resolution visualisation of disease morphology and provides a promising horizon for early disease detection and efficient therapeutic follow-up. However, definite conclusions from morphologic parameters are still lacking, and valid biomarkers have yet to be identified to provide a practical base for disease management. The European Society of Retina Specialists offers expert guidance for diagnostic and therapeutic management of neovascular AMD supporting healthcare givers and doctors in providing the best state-of-the-art care to their patients. Trial registration number NCT01318941. PMID:25136079

  6. Fibroblast-Specific Deletion of Hypoxia Inducible Factor-1 Critically Impairs Murine Cutaneous Neovascularization and Wound Healing.

    Science.gov (United States)

    Duscher, Dominik; Maan, Zeshaan N; Whittam, Alexander J; Sorkin, Michael; Hu, Michael S; Walmsley, Graham G; Baker, Hutton; Fischer, Lauren H; Januszyk, Michael; Wong, Victor W; Gurtner, Geoffrey C

    2015-11-01

    Diabetes and aging are known risk factors for impaired neovascularization in response to ischemic insult, resulting in chronic wounds, and poor outcomes following myocardial infarction and cerebrovascular injury. Hypoxia-inducible factor (HIF)-1α, has been identified as a critical regulator of the response to ischemic injury and is dysfunctional in diabetic and elderly patients. To better understand the role of this master hypoxia regulator within cutaneous tissue, the authors generated and evaluated a fibroblast-specific HIF-1α knockout mouse model. The authors generated floxed HIF-1 mice (HIF-1) by introducing loxP sites around exon 1 of the HIF-1 allele in C57BL/6J mice. Fibroblast-restricted HIF-1α knockout (FbKO) mice were generated by breeding our HIF-1 with tamoxifen-inducible Col1a2-Cre mice (Col1a2-CreER). HIF-1α knockout was evaluated on a DNA, RNA, and protein level. Knockout and wild-type mice were subjected to ischemic flap and wound healing models, and CD31 immunohistochemistry was performed to assess vascularity of healed wounds. Quantitative real-time polymerase chain reaction of FbKO skin demonstrated significantly reduced Hif1 and Vegfa expression compared with wild-type. This finding was confirmed at the protein level (p wound closure and vascularity (p wound healing, reduced wound vascularity, and significant impairment in the ischemic neovascular response. These findings provide new insight into the importance of cell-specific responses to hypoxia during cutaneous neovascularization.

  7. Efficacy and safety of intravitreal bevacizumab in eyes with neovascular glaucoma undergoing Ahmed glaucoma valve implantation: 2-year follow-up.

    Science.gov (United States)

    Arcieri, Enyr S; Paula, Jayter S; Jorge, Rodrigo; Barella, Kleyton A; Arcieri, Rafael S; Secches, Danilo J; Costa, Vital P

    2015-02-01

    To evaluate the efficacy and safety of intravitreal bevacizumab (IVB) in eyes with neovascular glaucoma (NVG) undergoing Ahmed glaucoma valve (AGV) implantation. This was a multicentre, prospective, randomized clinical trial that enrolled 40 patients with uncontrolled neovascular glaucoma that had undergone panretinal photocoagulation and required glaucoma drainage device implantation. Patients were randomized to receive IVB (1.25 mg) or not during Ahmed valve implant surgery. Injections were administered intra-operatively, and 4 and 8 weeks after surgery. After a mean follow-up of 2.25 ± 0.67 years (range 1.5-3 years), both groups showed a significant decrease in IOP (p glaucoma undergoing Ahmed glaucoma valve implantation. There is a trend to slightly lower IOPs and number of medications with IVB use during AGV implantation for neovascular glaucoma. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  8. Combination therapy of low-fluence photodynamic therapy and intravitreal ranibizumab for choroidal neovascular membrane in choroidal osteoma

    Directory of Open Access Journals (Sweden)

    Rodney J Morris

    2011-01-01

    Full Text Available Choroidal osteoma is an unusual form of intraocular calcification seen in otherwise healthy eyes. It is a benign idiopathic osseous tumor of the choroid, typically seen in young females. Choroidal neovascular membrane (CNVM is a complication seen in one-third of these patients and carries a poor visual outcome. We report a case of a 25-year-old hyperthyroid female with choroidal osteoma and subfoveal CNVM in her left eye which was successfully treated using low-fluence photodynamic therapy (PDT with verteporfin followed by a single injection of intravitreal ranibizumab.

  9. Clinical characteristics of reticular pseudodrusen in the fellow eye of patients with unilateral neovascular age-related macular degeneration.

    Science.gov (United States)

    Hogg, Ruth E; Silva, Rufino; Staurenghi, Giovanni; Murphy, George; Santos, Ana R; Rosina, Chiara; Chakravarthy, Usha

    2014-09-01

    To describe associations between reticular pseudodrusen, individual characteristics, and retinal function. Cohort study. We recruited 105 patients (age range, 52-93 years) who had advanced neovascular age-related macular degeneration (AMD) in only 1 eye from 3 clinical centers in Europe. Minimum follow-up was 12 months. The eye selected for study was the fellow eye without advanced disease. Clinical measures of vision were distance visual acuity, near visual acuity, and results of the Smith-Kettlewell low-luminance acuity test (SKILL). Fundus imaging included color photography, red-free imaging, blue autofluorescence imaging, fluorescein angiography, indocyanine green angiography, and optical coherence tomography using standardized protocols. These were used to detect progression to neovascular AMD in the study eye during follow-up. All imaging outputs were graded for the presence or absence of reticular pseudodrusen (RPD) using a multimodal approach. Choroidal thickness was measured at the foveal center and at 2 other equidistant locations from the fovea (1500 μm) nasally and temporally. Metrics on retinal thickness and volume were obtained from the manufacturer-supplied automated segmentation readouts. Presence of RPD, distance visual acuity, near visual acuity, SKILL score, choroidal thickness, retinal thickness, and retinal volume. Reticular pseudodrusen was found in 43 participants (41%) on 1 or more imaging method. The SKILL score was significantly worse in those with reticular drusen (mean score ± standard deviation [SD, 38±12) versus those without (mean score ± SD, 33±9) (P = 0.034). Parafoveal retinal thickness, parafoveal retinal volume, and all of the choroidal thickness parameters measured were significantly lower in those with reticular drusen than in those without. The presence of RPD was associated with development of neovascular AMD when corrected for age and sex (odds ratio, 5.5; 95% confidence interval, 1.1-28.8; P = 0.042). All participants

  10. Suicide gene reveals the myocardial neovascularization role of mesenchymal stem cells overexpressing CXCR4 (MSC(CXCR4.

    Directory of Open Access Journals (Sweden)

    Jialiang Liang

    Full Text Available BACKGROUND: Our previous studies indicated that MSC(CXCR4 improved cardiac function after myocardial infarction (MI. This study was aimed to investigate the specific role of MSC(CXCR4 in neovascularization of infarcted myocardium using a suicide gene approach. METHODS: MSCs were transduced with either lentivirus-null vector/GFP (MSC(Null as control or vector encoding for overexpressing CXCR4/GFP. The MSC derived-endothelial cell (EC differentiation was assessed by a tube formation assay, Dil-ac-LDL uptake, EC marker expression, and VE-cadherin promoter activity assay. Gene expression was analyzed by quantitative RT-PCR or Western blot. The suicide gene approach was under the control of VE-cadherin promoter. In vivo studies: Cell patches containing MSC(Null or MSC(CXCR4 were transduced with suicide gene and implanted into the myocardium of MI rat. Rats received either ganciclovir (GCV or vehicle after cell implantation. After one month, the cardiac functional changes and neovascularization were assessed by echocardiography, histological analysis, and micro-CT imaging. RESULTS: The expression of VEGF-A and HIF-1α was significantly higher in MSC(CXCR4 as compared to MSC(Null under hypoxia. Additionally, MSC(CXCR4 enhanced new vessel formation and EC differentiation, as well as STAT3 phosphorylation under hypoxia. STAT3 participated in the transcription of VE-cadherin in MSC(CXCR4 under hypoxia, which was inhibited by WP1066 (a STAT3 inhibitor. In addition, GCV specifically induced death of ECs with suicide gene activation. In vivo studies: MSC(CXCR4 implantation promoted cardiac functional restoration, reduced infarct size, improved cardiac remodeling, and enhanced neovascularization in ischemic heart tissue. New vessels derived from MSC(CXCR4 were observed at the injured heart margins and communicated with native coronary arteries. However, the derived vessel networks were reduced by GCV, reversing improvement of cardiac function. CONCLUSION: The

  11. Electrophysiological assessment of retinal function during 6 months of bevacizumab treatment in neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Pedersen, Karen Bjerg; Møller, Flemming; Sjølie, Anne Katrin

    2010-01-01

    PURPOSE: The purpose of this study was to assess the alteration of retinal function by multifocal electroretinography and full-field electroretinography in patients with age-related macular degeneration treated with bevacizumab. METHODS: We performed a prospective pilot study of 26 eyes of 26...... previously treatment-naïve patients with neovascular age-related macular degeneration receiving intravitreal injections with 1.25 mg bevacizumab. Patients were examined with multifocal electroretinography, full-field electroretinography, optical coherence tomography, and visual acuity. Follow...

  12. Uncovering the Number and Clonal Dynamics of Mesp1 Progenitors during Heart Morphogenesis

    Directory of Open Access Journals (Sweden)

    Samira Chabab

    2016-01-01

    Full Text Available The heart arises from distinct sources of cardiac progenitors that independently express Mesp1 during gastrulation. The precise number of Mesp1 progenitors that are specified during the early stage of gastrulation, and their clonal behavior during heart morphogenesis, is currently unknown. Here, we used clonal and mosaic tracing of Mesp1-expressing cells combined with quantitative biophysical analysis of the clonal data to define the number of cardiac progenitors and their mode of growth during heart development. Our data indicate that the myocardial layer of the heart derive from ∼250 Mesp1-expressing cardiac progenitors born during gastrulation. Despite arising at different time points and contributing to different heart regions, the temporally distinct cardiac progenitors present very similar clonal dynamics. These results provide insights into the number of cardiac progenitors and their mode of growth and open up avenues to decipher the clonal dynamics of progenitors in other organs and tissues.

  13. PROGENITOR-EXPLOSION CONNECTION AND REMNANT BIRTH MASSES FOR NEUTRINO-DRIVEN SUPERNOVAE OF IRON-CORE PROGENITORS

    Energy Technology Data Exchange (ETDEWEB)

    Ugliano, Marcella; Janka, Hans-Thomas; Marek, Andreas [Max-Planck-Institut fuer Astrophysik, Karl-Schwarzschild-Str. 1, D-85748 Garching (Germany); Arcones, Almudena [Institut fuer Kernphysik, Technische Universitaet Darmstadt, Schlossgartenstr. 2, D-64289 Darmstadt (Germany)

    2012-09-20

    We perform hydrodynamic supernova (SN) simulations in spherical symmetry for over 100 single stars of solar metallicity to explore the progenitor-explosion and progenitor-remnant connections established by the neutrino-driven mechanism. We use an approximative treatment of neutrino transport and replace the high-density interior of the neutron star (NS) by an inner boundary condition based on an analytic proto-NS core-cooling model, whose free parameters are chosen such that explosion energy, nickel production, and energy release by the compact remnant of progenitors around 20 M{sub Sun} are compatible with SN 1987A. Thus, we are able to simulate the accretion phase, initiation of the explosion, subsequent neutrino-driven wind phase for 15-20 s, and the further evolution of the blast wave for hours to days until fallback is completed. Our results challenge long-standing paradigms. We find that remnant mass, launch time, and properties of the explosion depend strongly on the stellar structure and exhibit large variability even in narrow intervals of the progenitors' zero-age main-sequence mass. While all progenitors with masses below {approx}15 M{sub Sun} yield NSs, black hole (BH) as well as NS formation is possible for more massive stars, where partial loss of the hydrogen envelope leads to weak reverse shocks and weak fallback. Our NS baryonic masses of {approx}1.2-2.0 M{sub Sun} and BH masses >6 M{sub Sun} are compatible with a possible lack of low-mass BHs in the empirical distribution. Neutrino heating accounts for SN energies between some 10{sup 50} erg and {approx}2 Multiplication-Sign 10{sup 51} erg but can hardly explain more energetic explosions and nickel masses higher than 0.1-0.2 M{sub Sun }. These seem to require an alternative SN mechanism.

  14. Suppression of Retinal Neovascularization in vivo by Inhibition of Vascular Endothelial Growth Factor (VEGF) Using Soluble VEGF-Receptor Chimeric Proteins

    Science.gov (United States)

    Aiello, Lloyd Paul; Pierce, Eric A.; Foley, Eliot D.; Takagi, Hitoshi; Chen, Helen; Riddle, Lavon; Ferrara, Napoleone; King, George L.; Smith, Lois E. H.

    1995-11-01

    The majority of severe visual loss in the United States results from complications associated with retinal neovascularization in patients with ischemic ocular diseases such as diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity. Intraocular expression of the angiogenic protein vascular endothelial growth factor (VEGF) is closely correlated with neovascularization in these human disorders and with ischemia-induced retinal neovascularization in mice. In this study, we evaluated whether in vivo inhibition of VEGF action could suppress retinal neovascularization in a murine model of ischemic retinopathy. VEGF-neutralizing chimeric proteins were constructed by joining the extracellular domain of either human (Flt) or mouse (Flk) high-affinity VEGF receptors with IgG. Control chimeric proteins that did not bind VEGF were also used. VEGF-receptor chimeric proteins eliminated in vitro retinal endothelial cell growth stimulation by either VEGF (P hypoxic conditioned medium (P < 0.005) without affecting growth under nonstimulated conditions. Control proteins had no effect. To assess in vivo response, animals with bilateral retinal ischemia received intravitreal injections of VEGF antagonist in one eye and control protein in the contralateral eye. Retinal neovascularization was quantitated histologically by a masked protocol. Retinal neovascularization in the eye injected with human Flt or murine Flk chimeric protein was reduced in 100% (25/25; P < 0.0001) and 95% (21/22; P < 0.0001) of animals, respectively, compared to the control treated eye. This response was evident after only a single intravitreal injection and was dose dependent with suppression of neovascularization noted after total delivery of 200 ng of protein (P < 0.002). Reduction of histologically evident neovascular nuclei per 6-um section averaged 47% ± 4% (P < 0.001) and 37% ± 2% (P < 0.001) for Flt and Flk chimeric proteins with maximal inhibitory effects of 77% and 66

  15. CD8+ T cells induce thyroid epithelial cell hyperplasia and fibrosis.

    Science.gov (United States)

    Yu, Shiguang; Fang, Yujiang; Sharav, Tumenjargal; Sharp, Gordon C; Braley-Mullen, Helen

    2011-02-15

    CD8(+) T cells can be important effector cells in autoimmune inflammation, generally because they can damage target cells by cytotoxicity. This study shows that activated CD8(+) T cells induce thyroid epithelial cell hyperplasia and proliferation and fibrosis in IFN-γ(-/-) NOD.H-2h4 SCID mice in the absence of CD4(+) T cells. Because CD8(+) T cells induce proliferation rather than cytotoxicity of target cells, these results describe a novel function for CD8(+) T cells in autoimmune disease. In contrast to the ability of purified CD8(+) T cells to induce thyrocyte proliferation, CD4(+) T cells or CD8 T cell-depleted splenocytes induced only mild thyroid lesions in SCID recipients. T cells in both spleens and thyroids highly produce TNF-α. TNF-α promotes proliferation of thyrocytes in vitro, and anti-TNF-α inhibits development of thyroid epithelial cell hyperplasia and proliferation in SCID recipients of IFN-γ(-/-) splenocytes. This suggests that targeting CD8(+) T cells and/or TNF-α may be effective for treating epithelial cell hyperplasia and fibrosis.

  16. Liver sinusoidal endothelial cells induce immunosuppressive IL-10-producing Th1 cells via the Notch pathway.

    Science.gov (United States)

    Neumann, Katrin; Rudolph, Christine; Neumann, Christian; Janke, Marko; Amsen, Derk; Scheffold, Alexander

    2015-07-01

    Under homeostasis, liver sinusoidal endothelial cells (LSECs) shift intrahepatic T-cell responses towards tolerance. However, the role of LSECs in the regulation of T-cell-induced liver inflammation is less clear. Here, we studied the capacity of LSECs to modulate pro-inflammatory Th1-cell differentiation in mice. Using in vitro co-culture systems and subsequent cytokine analysis, we showed that LSECs induced high amounts of the anti-inflammatory cytokine IL-10 in developing Th1 cells. These LSEC-stimulated Th1 cells had no pro-inflammatory capacity in vivo but instead actively suppressed an inflammatory Th1-cell-induced delayed-type hypersensitivity reaction. Blockage of IL-10 signaling in vivo inhibited immunosuppressive activity of LSEC-stimulated Th1 cells. We identified the Notch pathway as a mechanism how LSECs trigger IL-10 expression in Th1 cells. LSECs expressed high levels of the Delta-like and Jagged family of Notch ligands and induced expression of the Notch target genes hes-1 and deltex-1 in Th1 cells. Blockade of Notch signaling selectively inhibited IL-10 induction in Th1 cells by LSECs. Our findings suggest that LSEC-induced IL-10 expression in Th1 cells via the Notch pathway may contribute to the control of hepatic inflammatory immune responses by induction of a self-regulatory mechanism in pro-inflammatory Th1 cells. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Dasatinib inhibits both osteoclast activation and prostate cancer PC-3-cell-induced osteoclast formation.

    Science.gov (United States)

    Araujo, John C; Poblenz, Ann; Corn, Paul; Parikh, Nila U; Starbuck, Michael W; Thompson, Jerry T; Lee, Francis; Logothetis, Christopher J; Darnay, Bryant G

    2009-11-01

    Therapies to target prostate cancer bone metastases have only limited effects. New treatments are focused on the interaction between cancer cells, bone marrow cells and the bone matrix. Osteoclasts play an important role in the development of bone tumors caused by prostate cancer. Since Src kinase has been shown to be necessary for osteoclast function, we hypothesized that dasatinib, a Src family kinase inhibitor, would reduce osteoclast activity and prostate cancer (PC-3) cell-induced osteoclast formation. Dasatinib inhibited RANKL-induced osteoclast differentiation of bone marrow-derived monocytes with an EC(50) of 7.5 nM. PC-3 cells, a human prostate cancer cell line, were able to differentiate RAW 264.7 cells, a murine monocytic cell line, into osteoclasts, and dasatinib inhibited this differentiation. In addition, conditioned medium from PC-3 cell cultures was able to differentiate RAW 264.7 cells into osteoclasts and this too, was inhibited by dasatinib. Even the lowest concentration of dasatinib, 1.25 nmol, inhibited osteoclast differentiation by 29%. Moreover, dasatinib inhibited osteoclast activity by 58% as measured by collagen 1 release. We performed in vitro experiments utilizing the Src family kinase inhibitor dasatinib to target osteoclast activation as a means of inhibiting prostate cancer bone metastases. Dasatinib inhibits osteoclast differentiation of mouse primary bone marrow-derived monocytes and PC-3 cell-induced osteoclast differentiation. Dasatinib also inhibits osteoclast degradation activity. Inhibiting osteoclast differentiation and activity may be an effective targeted therapy in patients with prostate cancer bone metastases.

  18. Single progenitor model for GW150914 and GW170104

    Science.gov (United States)

    D'Orazio, Daniel J.; Loeb, Abraham

    2018-04-01

    The merger of stellar-mass black holes (BHs) is not expected to generate detectable electromagnetic (EM) emission. However, the gravitational wave (GW) events GW150914 and GW170104, detected by the Laser Interferometer Gravitational Wave Observatory to be the result of merging, ˜60 M⊙ binary black holes (BBHs), each have claimed coincident gamma-ray emission. Motivated by the intriguing possibility of an EM counterpart to BBH mergers, we construct a model that can reproduce the observed EM and GW signals for GW150914- and GW170104-like events, from a single-star progenitor. Following Loeb [Astrophys. J. Lett. 819, L21 (2016), 10.3847/2041-8205/819/2/L21], we envision a massive, rapidly rotating star within which a rotating-bar instability fractures the core into two overdensities that fragment into clumps which merge to form BHs in a tight binary with arbitrary spin-orbit alignment. Once formed, the BBH inspirals due to gas and gravitational-wave drag until tidal forces trigger strong feeding of the BHs with the surrounding stellar-density gas about 10 sec before merger. The resulting giga-Eddington accretion peak launches a jet that breaks out of the progenitor star and drives a powerful outflow that clears the gas from the orbit of the binary within 1 sec, preserving the vacuum GW waveform in the Laser Interferometer Gravitational Wave Observatory band. The single-progenitor scenario predicts the existence of variability of the gamma-ray burst, modulated at the ˜0.2 sec chirping period of the BBH due to relativistic Doppler boost. The jet breakout should be accompanied by a low-luminosity supernova. Finally, because the BBHs of the single-progenitor model do not exist at large separations, they will not be detectable in the low-frequency gravitational-wave band of the Laser Interferometer Space Antenna. Hence, the single-progenitor BBHs will be unambiguously discernible from BBHs formed through alternate, double-progenitor evolution scenarios.

  19. Comparative analysis of circulating endothelial progenitor cells in age-related macular degeneration patients using automated rare cell analysis (ARCA and fluorescence activated cell sorting (FACS.

    Directory of Open Access Journals (Sweden)

    Emil Anthony T Say

    Full Text Available BACKGROUND: Patients with age-related macular degeneration (ARMD begin with non-neovascular (NNV phenotypes usually associated with good vision. Approximately 20% of NNV-ARMD patients will convert to vision debilitating neovascular (NV ARMD, but precise timing of this event is unknown. Developing a clinical test predicting impending conversion to NV-ARMD is necessary to prevent vision loss. Endothelial progenitor cells (EPCs, defined as CD34(+VEGR2(+ using traditional fluorescence activated cell sorting (FACS, are rare cell populations known to be elevated in patients with NV-ARMD compared to NNV-ARMD. FACS has high inter-observer variability and subjectivity when measuring rare cell populations precluding development into a diagnostic test. We hypothesized that automated rare cell analysis (ARCA, a validated and FDA-approved technology for reproducible rare cell identification, can enumerate EPCs in ARMD patients more reliably. This pilot study serves as the first step in developing methods for reproducibly predicting ARMD phenotype conversion. METHODS: We obtained peripheral venous blood samples in 23 subjects with NNV-ARMD or treatment naïve NV-ARMD. Strict criteria were used to exclude subjects with known angiogenic diseases to minimize confounding results. Blood samples were analyzed in masked fashion in two separate laboratories. EPCs were independently enumerated using ARCA and FACS within 24 hours of blood sample collection, and p<0.2 was considered indicative of a trend for this proof of concept study, while statistical significance was established at 0.05. RESULTS: We measured levels of CD34(+VEGFR2(+ EPCs suggestive of a trend with higher values in patients with NV compared to NNV-ARMD (p = 0.17 using ARCA. Interestingly, CD34(+VEGR2(+ EPC analysis using FACS did not produce similar results (p = 0.94. CONCLUSIONS: CD34(+VEGR2(+ may have predictive value for EPC enumeration in future ARCA studies. EPC measurements in a small sample

  20. Comparative analysis of circulating endothelial progenitor cells in age-related macular degeneration patients using automated rare cell analysis (ARCA) and fluorescence activated cell sorting (FACS).

    Science.gov (United States)

    Say, Emil Anthony T; Melamud, Alex; Esserman, Denise Ann; Povsic, Thomas J; Chavala, Sai H

    2013-01-01

    Patients with age-related macular degeneration (ARMD) begin with non-neovascular (NNV) phenotypes usually associated with good vision. Approximately 20% of NNV-ARMD patients will convert to vision debilitating neovascular (NV) ARMD, but precise timing of this event is unknown. Developing a clinical test predicting impending conversion to NV-ARMD is necessary to prevent vision loss. Endothelial progenitor cells (EPCs), defined as CD34(+)VEGR2(+) using traditional fluorescence activated cell sorting (FACS), are rare cell populations known to be elevated in patients with NV-ARMD compared to NNV-ARMD. FACS has high inter-observer variability and subjectivity when measuring rare cell populations precluding development into a diagnostic test. We hypothesized that automated rare cell analysis (ARCA), a validated and FDA-approved technology for reproducible rare cell identification, can enumerate EPCs in ARMD patients more reliably. This pilot study serves as the first step in developing methods for reproducibly predicting ARMD phenotype conversion. We obtained peripheral venous blood samples in 23 subjects with NNV-ARMD or treatment naïve NV-ARMD. Strict criteria were used to exclude subjects with known angiogenic diseases to minimize confounding results. Blood samples were analyzed in masked fashion in two separate laboratories. EPCs were independently enumerated using ARCA and FACS within 24 hours of blood sample collection, and ptrend for this proof of concept study, while statistical significance was established at 0.05. We measured levels of CD34(+)VEGFR2(+) EPCs suggestive of a trend with higher values in patients with NV compared to NNV-ARMD (p = 0.17) using ARCA. Interestingly, CD34(+)VEGR2(+) EPC analysis using FACS did not produce similar results (p = 0.94). CD34(+)VEGR2(+) may have predictive value for EPC enumeration in future ARCA studies. EPC measurements in a small sample size were suggestive of a trend in ARMD using ARCA but not FACS. ARCA could be a

  1. La violencia de hijos adolescentes contra sus progenitores La violencia de hijos adolescentes contra sus progenitores

    Directory of Open Access Journals (Sweden)

    Concepción Aroca Montolío

    2013-10-01

    Full Text Available According to Prosecutor’s Office of the Minor, the accusation interposed by mothers and/or fathers victims by theirs children, along 2007 were 2603, in 2008 amounted 4.211, in 2009 there were 5.209 and in 2010 there were 8.000 accusations. Suede this worrying increase, the principal aim of our article is to check the scientific international and national documentation, from 1957 until the year 2010 that analyses the phenomenon of the adolescent violence against parents, to achieve an approximation to its keys that there allows us the comprehension and analysis of this serious familiar problem. For it we will analyse: (a the importance of this crime by means of criminological mediators: prevalence and incidence; (b the age and sex variables’ aggressors to be able to establish a basic profile about theirs and, (c the violence types that the teenagers wield to damage, prejudice and suffering against their progenitors, with the aim to obtain what they want. The information obtained in this research review and qualitative analysis, change in base to the methodology used and the type of sample under study to obtain conclusions. Even though, we wantto do research into needs to investigate this type of familiar violence, and from there, to do researches with rigorous scientific methodologies, unifying criteria and variables to be investigating, to be able to anticipate in this increasing problem that the parents have. Según la Fiscalía del Menor en el año 2007, las denuncias interpuestas por madres y/o padres, víctimas de malos tratos por sus hijos e hijas menores de edad, fueron 2.683. En 2008 ascendieron a 4.211, en 2009 se presentaron 5.209 y en el año 2010 se registraron 8.000 denuncias. Ante éste preocupante incremento, el objetivo principal de nuestro artículo es revisar la documentación científica que analiza la violencia filio-parental,  desde 1957 hasta el año 2011, para lograr una aproximación a sus claves que nos permita la

  2. Small laser spot versus standard laser spot photodynamic therapy for idiopathic choroidal neovascularization: a randomized controlled study.

    Science.gov (United States)

    Li, Xiao-xin; Tao, Yong

    2012-12-01

    Idiopathic choroidal neovascularization (ICNV) affects young patients and thus may have a significant impact on vision and life quality over a patient's lifespan. This study was designed to compare the visual outcome and retinal pigment epithelium (RPE) damage after photodynamic therapy (PDT) with small laser spot and PDT with standard laser spot for idiopathic choroidal neovascularization (ICNV). This was a randomized controlled study. Fifty-two patients with ICNV were enrolled and randomly divided into a study group (small laser spot PDT, n = 27) and a control group (standard laser spot PDT, n = 25). Best corrected visual acuity (BCVA), optic coherence tomography (OCT) and fluorescein angiography (FA) findings were the main measurements. The patients were followed up 1 week, 1, 3, 6, 9 months and 1 year after PDT. BCVA improvement was statistically significantly higher in the study group than the control group at 6-month ((25.53 ± 15.01) letters vs. (14.71 ± 11.66) letters, P = 0.025) and 9-month follow-ups ((27.53 ± 17.78) letters vs. (15.59 ± 12.21) letters, P = 0.039). At 3- and 6-month follow-ups, the quadrants of RPE damage between the two groups varied significantly (P laser spot PDT group than in the standard laser spot PDT group for ICNV.

  3. Efficacy of Intravitreal injection of 2-Methoxyestradiol in regression of neovascularization of a retinopathy of prematurity rat model.

    Science.gov (United States)

    Said, Azza Mohamed Ahmed; Zaki, Rania Gamal Eldin; Salah Eldin, Rania A; Nasr, Maha; Azab, Samar Saad; Elzankalony, Yaser Abdelmageuid

    2017-04-04

    Retinopathy of prematurity (ROP) is one of the targets for early detection and treatment to prevent childhood blindness in world health organization programs. The purpose of study was to evaluate the efficacy of intravitreal injection of 2-Methoxyestradiol (2-ME) nanoemulsion in regressing neovascularization of a ROP rat model. A prospective comparative case - control animal study conducted on 56 eyes of 28 healthy new born Sprague Dawley male albino rat. ROP was induced in 21 rats then two concentrations of 2-ME nanoparticles were injected in right eyes of 14 rats (low dose; study group I, high dose; study group II). A blank nanoemulsion was injected in the right eyes of seven rats (control positive group I). No injections performed in contralateral left eyes (control positive group II). Seven rats (14 eyes) were kept in room air (control negative group). On postnatal day 17, eyeballs were enucleated. Histological structure of the retina was examined using Hematoxylin and eosin staining. Vascular endothelial growth factor (VEGF) and glial fibrillary acidic protein (GFAP) expressions were detected by immunohistochemical studies. Intravitreal injection of 2-ME (in the two concentrations) caused marked regression of the new vascular tufts on the vitreal side with normal organization and thickness of the retina especially in study group II, which also show negative VEGF immunoreaction. Positive GFAP expression was detected in the control positive groups and study group (I). Intravitreal injection of 2-Methoxyestradiol nanoemulsion is a promising effective method in reduction of neovascularization of a ROP rat model.

  4. Laparoscopic ischemic conditioning of the stomach increases neovascularization of the gastric conduit in patients undergoing esophagectomy for cancer.

    Science.gov (United States)

    Pham, Thai H; Melton, Shelby D; McLaren, Patrick J; Mokdad, Ali A; Huerta, Sergio; Wang, David H; Perry, Kyle A; Hardaker, Hope L; Dolan, James P

    2017-09-01

    Gastric ischemic preconditioning has been proposed to improve blood flow and reduce the incidence of anastomotic complications following esophagectomy with gastric pull-up. This study aimed to evaluate the effect of prolonged ischemic preconditioning on the degree of neovascularization in the distal gastric conduit at the time of esophagectomy. A retrospective review of a prospectively maintained database identified 30 patients who underwent esophagectomy. The patients were divided into three groups: control (no preconditioning, n = 9), partial (short gastric vessel ligation only, n = 8), and complete ischemic preconditioning (left and short gastric vessel ligation, n = 13). Microvessel counts were assessed, using immunohistologic analysis to determine the degree of neovascularization at the distal gastric margin. The groups did not differ in age, gender, BMI, pathologic stage, or cancer subtype. Ischemic preconditioning durations were 163 ± 156 days for partial ischemic preconditioning, compared to 95 ± 50 days for complete ischemic preconditioning (P = 0.2). Immunohistologic analysis demonstrated an increase in microvessel counts of 29% following partial ischemic preconditioning (P = 0.3) and 67% after complete ischemic preconditioning (P gastric conduit. © 2017 Wiley Periodicals, Inc.

  5. Long-term outcome after radiation therapy for subfoveal choroidal neovascularization associated with age-related macular degeneration

    International Nuclear Information System (INIS)

    Mandai, Michiko; Takahashi, Masayo; Miyamoto, Hideki; Hiroshiba, Naoko; Kimura, Hideya; Ogura, Yuichiro; Honda, Yoshihito; Sasai, Keisuke

    2000-01-01

    The purpose of this study was to investigate the long-term effect of low-dose radiation therapy on subfoveal choroidal neovascularization associated with age-related macular degeneration. The clinical course and visual outcome were compared retrospectively among two treated groups and a control group; 15 patients (15 eyes) received 10 Gy, another 15 patients (15 eyes) received 20 Gy. The control group consisted of 15 patients (15 eyes) without treatment. All patients were followed up for at least 18 months, and most were followed up for 3 years. The macula was irradiated with either 10 Gy in 5 fractions or with 20 Gy in 10 fractions after computed tomography (CT) simulation enabled real-time treatment planning from multiple CT slices. During the 3 years of follow-up, the lesions became better in 5 eyes, unchanged in 1, and worse in 9 with 10 Gy radiation; better in 7 eyes, unchanged in 1, and worse in 7 eyes with 20 Gy; and better in 1 eye and worse in 14 with no treatment. The difference between the groups treated with radiation and the control was statistically significant (P<.05). Visual acuity was also significantly better in the group receiving 20 Gy than in the control group up to 2 years after radiation (P<.01). Radiation may extend the period of good visual function substantially by reducing subfoveal choroidal neovascularization activity. (author)

  6. Clinical experience with fixed bimonthly aflibercept dosing in treatment-experienced patients with neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Khanani AM

    2015-07-01

    Full Text Available Arshad M Khanani Sierra Eye Associates, Reno, NV, USA Purpose: To evaluate the durability of fixed bimonthly dosing of intravitreal aflibercept for neovascular age-related macular degeneration.Methods: Records of 16 patients were retrospectively reviewed. Patients received three initial 2.0 mg monthly doses of aflibercept then 8-weekly doses according to the product label. Best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study [ETDRS] letters, central macular thickness, fluid on optical coherence tomography, and pigment epithelial detachment (PED were measured.Results: Prior to starting aflibercept, 13 patients had subretinal fluid (SRF, five had intraretinal fluid (IRF, four had PED, and baseline visual acuity (VA was 62 approximate ETDRS letters. Following the monthly dosing, seven patients had no improvement or decreased VA, ten patients still had SRF/IRF, and PED had worsened in one patient. At Visit 4, an average of 6.8 weeks after Visit 3, VA had decreased in seven patients, SRF/IRF had increased in 12 patients, and PED had returned in all patients who initially responded. Based on the presence of fluid after the initial monthly injections, 12 patients could not be extended to fixed bimonthly dosing.Conclusion: This case series adds to the growing body of evidence on the need for flexible dosing schedules for the personalized treatment of neovascular age-related macular degeneration. Keywords: age-related macular degeneration, AMD, bimonthly, regimen, aflibercept, case studies, retinal fluid

  7. Long-term outcome after radiation therapy for subfoveal choroidal neovascularization associated with age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Mandai, Michiko; Takahashi, Masayo; Miyamoto, Hideki; Hiroshiba, Naoko; Kimura, Hideya; Ogura, Yuichiro; Honda, Yoshihito; Sasai, Keisuke [Kyoto Univ. (Japan). Graduate School of Medicine

    2000-10-01

    The purpose of this study was to investigate the long-term effect of low-dose radiation therapy on subfoveal choroidal neovascularization associated with age-related macular degeneration. The clinical course and visual outcome were compared retrospectively among two treated groups and a control group; 15 patients (15 eyes) received 10 Gy, another 15 patients (15 eyes) received 20 Gy. The control group consisted of 15 patients (15 eyes) without treatment. All patients were followed up for at least 18 months, and most were followed up for 3 years. The macula was irradiated with either 10 Gy in 5 fractions or with 20 Gy in 10 fractions after computed tomography (CT) simulation enabled real-time treatment planning from multiple CT slices. During the 3 years of follow-up, the lesions became better in 5 eyes, unchanged in 1, and worse in 9 with 10 Gy radiation; better in 7 eyes, unchanged in 1, and worse in 7 eyes with 20 Gy; and better in 1 eye and worse in 14 with no treatment. The difference between the groups treated with radiation and the control was statistically significant (P<.05). Visual acuity was also significantly better in the group receiving 20 Gy than in the control group up to 2 years after radiation (P<.01). Radiation may extend the period of good visual function substantially by reducing subfoveal choroidal neovascularization activity. (author)

  8. Treatment of age-related subfoveal neovascular membranes by teletherapy. Results of a non-randomized study

    Energy Technology Data Exchange (ETDEWEB)

    Subasi, M.; Akmansu, M.; Or, M. [Gazi Univ., Ankara (Turkey). Medical Faculty

    1999-03-01

    This investigation was designed to determine whether low-dose radiation to the macular region could influence the natural course of age-related subfoveal neovascularization. Thirty-one patients with subfoveal membranes due to age-related macular degeneration (ARMD) were treated with 12 Gy of 6 MV X-rays, and 72 patients who were untreated served as a control group. Both groups were followed-up. At six months of follow-up visual acuity was maintained in 54.8% and improved 25.8% of patients treated by radiotherapy. In the control group, visual acuity showed deterioration in 55.5%. There was a significant difference between the treated and untreated groups (p<0.01). Significant neovascular membrane regression or stabilization was recorded in 61.3% of treated patients at six months post-radiation, whereas the membranes in all. 72 control patients showed progressive enlargement. This non-randomized study suggested that low doses of radiation may be an alternative treatment for ARMD without an immediate drop in visual acuity or significant radiation morbidity. (author)

  9. The inhibitory effect of different concentrations of KH902 eye drops on corneal neovascularization induced by alkali burn

    Directory of Open Access Journals (Sweden)

    Yan Wu

    2017-01-01

    Full Text Available Purpose: The aim of this study was to evaluate the inhibitory effect of different concentrations of KH902 eye drops on rabbit corneal neovascularization (CNV induced by alkali burn. Methods: Forty-eight adult rabbits were randomized into four groups after alkali burning: Group A (2.5 mg/ml, Group B (5 mg/ml, and Group C (10 mg/ml by different concentrations of KH902 eye drops and Group D by saline solution as control with three times a day for 2 weeks. At days 7, 14, and 28, the anterior segment photographs, confocal microscopy, and histopathology were performed to evaluate corneal opacity, neovascularization, inflammatory cell density, vessel size, and edema. Immunohistochemistry was applied to analyze the vascular endothelial growth factor (VEGF level. Results: (1 The CNV in the medicine-treated groups showed a reduction without obvious corneal side effects histologically. (2 Compared to the control group, the three medicine-treated groups showed a reduction in the VEGF levels and CNV areas on days 7, 14, and 28 and in the inflammatory cell density on days 14 and 28 (P 0.05. Conclusion: KH902 eye drops in lower concentration showed an obvious reduction of the CNV growing for rabbit corneal alkali burn without side effects.

  10. Evolution of Geographic Atrophy in Participants Treated with Ranibizumab for Neovascular Age-related Macular Degeneration.

    Science.gov (United States)

    Thavikulwat, Alisa T; Jacobs-El, Naima; Kim, Jane S; Agrón, Elvira; Hasan, Jesia; Meyerle, Catherine B; Valent, David; Cukras, Catherine A; Wiley, Henry E; Wong, Wai T; Chew, Emily Y

    2017-01-01

    To evaluate the risk factors, incidence, and rate of progression of geographic atrophy (GA) in eyes with neovascular age-related macular degeneration (nAMD) treated with ranibizumab. Post-hoc analysis of a prospective clinical study. 69 participants with nAMD in at least one eye. Participants were prospectively treated in the study eye with 0.5 mg intravitreal ranibizumab. Study eyes received 4 monthly injections followed by pro re nata injections until a fluid-free macula was achieved on optical coherence tomography. Risk factors assessed included baseline demographics, treatment, and ocular characteristics on imaging. Eyes were evaluated on fundus autofluorescence (FAF) for GA. The rate of GA area growth in study and fellow eyes was analyzed by linear regression of square-root transformed areas. Development of new-onset GA and rate of GA area growth measured on ocular imaging, including FAF images of the study eyes. Sixty-nine participants (mean age 78.8±7.8 years) with an average of 40.0±13.6 months of follow-up were analyzed. Twenty-two of 69 study eyes (32%) were treatment naïve. During their first year of the study, participants received an average of 9.2±3.3 injections in the study eye. Of 63 study eyes with quality baseline images, 22 (35%) had pre-existing GA. Of the remaining 41 eyes, 7 (17%) developed new-onset GA during study follow-up. Those who developed new GA were older (all ≥79 years old) and had received fewer study injections on average (6.9 vs. 10.4 injections at 1 year) compared to those who did not develop new GA. Of the 12 treatment naïve study eyes without GA at baseline, 1 (8.3%) developed new GA during the study. In 21 study eyes with quantifiable GA area, eyes with GA present at baseline (16/21) enlarged by 0.34±0.26 mm/year, compared to 0.19±0.12 mm/year in eyes developing new-onset GA (5/21). While 17% of study eyes without GA present at baseline receiving ranibizumab developed new GA, the role of ranibizumab in the development

  11. [Economic Short-Term Cost Model for Stereotactic Radiotherapy of Neovascular AMD].

    Science.gov (United States)

    Neubauer, A S; Reznicek, L; Minartz, C; Ziemssen, F

    2016-08-01

    Stereotactic radiation therapy (Oraya, OT) is available as a second line therapy for patients who, despite intensive anti-VEGF therapy for neovascular AMD, do not show an improvement in CNV. As OT is expensive (5,308 €), the short term economics for starting this therapy were investigated. A short-term cost model was set up in MS Excel with a two year time horizon. On the basis of the data of the randomised, controlled INTREPID pivotal trial and current treatment practice in Germany, the costs were compared of conventional anti-VEGF therapy, with or without a single OT treatment. Patients with an active lesion after initial anti-VEGF therapy and a maximum lesion diameter ≤ 4 mm were included. Modeled cost components/aspects were direct savings from injection number, control follow-up examinations and aids, as well as anti-VEGF switches. Costs for Germany were employed and a univariate sensitivity analysis was performed to address the existing uncertainty. For the patients with a maximum AMD lesion diameter ≤ 4 mm and a macula volume > 7.4 mm(3), the INTREPID trial showed a mean reduction of 3.68 intravitreal injections for 16 Gy radiation versus sham over a time period of 2 years. These 3.68 IVM result in ~ 4,500 € direct cost savings. Moreover, due to the higher response rate with 16 Gy radiation, the number of follow-up visits and aids can be reduced, which results in savings between 207 € and 1,224 € over 2 years. After radiation, fewer anti-VEGF switches for low or non-responders are expected, which is modeled to result in ~ 1.7 fewer injections over 2 years. Due to overall fewer injections, fewer endophthalmitis cases would be expected. However, endophthalmitis and microvascular abnormalities, which can be observed in a few cases, are associated with low or non-quantifiable costs in this cost-cost comparison model. In summary, cost reductions of between 6,400 and 8,500 € are predicted in the model over two years

  12. Comparison of intravitreal bevacizumab treatment between phakic and pseudophakic neovascular age-related macular degeneration.

    Science.gov (United States)

    Ozkaya, Abdullah; Alkin, Zeynep; Perente, Irfan; Yuksel, Kemal; Baz, Okkes; Alagoz, Cengiz; Yazici, Ahmet Taylan; Demirok, Ahmet

    2014-01-01

    Before the era of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment, only prevention for visual loss might have been achieved in a limited number of neovascular age-related macular generation (nAMD) patients with different treatment options. To compare the efficacy of intravitreal bevacizumab (IVB) for the treatment of nAMD between phakic and pseudophakic eyes. The newly diagnosed nAMD patients were included in this retrospective study. The patients were divided into the phakic and pseudophakic groups. Initially, the patients received three consecutive, monthly, IVB injections, and then the treatment was continued on an as-needed regimen. The patients were examined monthly, and the data at the baseline, at 3, 6, 9, and 12 months and at the last follow-up were evaluated. The changes in the visual acuity (VA), central retinal thickness (CRT) and the number of injections were compared between the two groups. The study included 62 eyes of 62 patients (39 phakic, and 23 pseudophakic patients). The mean follow-up time was 19.7 and 17.2 months in the phakic and pseudophakic groups, respectively (p=0.06). The mean Log MAR VA at the baseline, 12 months and the last follow-up was 0.82, 0.72 and 0.75 in the phakic group and 0.77, 0.67, and 0.68 in the pseudophakic group, respectively. The change in the mean BCVA from the baseline to 12 months and at the last follow-up was not statistically different between the two groups (p=0.9 and p=0.7, respectively). The mean injection number at 12 months was 4.5 and 4.9 in the phakic and pseudophakic group, respectively (p=0.2). The beneficial effect of IVB is equal in both the phakic and pseudophakic group of nAMD patients. The functional and anatomical outcomes of the treatment and the number of injections were similar in the two groups. © NEPjOPH.

  13. Progenitors of type Ia supernovae in elliptical galaxies

    International Nuclear Information System (INIS)

    Gilfanov, M.; Bogdan, A.

    2011-01-01

    Although there is a nearly universal agreement that type Ia supernovae are associated with the thermonuclear disruption of a CO white dwarf, the exact nature of their progenitors is still unknown. The single degenerate scenario envisages a white dwarf accreting matter from a non-degenerate companion in a binary system. Nuclear energy of the accreted matter is released in the form of electromagnetic radiation or gives rise to numerous classical nova explosions prior to the supernova event. We show that combined X-ray output of supernova progenitors and statistics of classical novae predicted in the single degenerate scenario are inconsistent with X-ray and optical observations of nearby early type galaxies and galaxy bulges. White dwarfs accreting from a donor star in a binary system and detonating at the Chandrasekhar mass limit can account for no more than ∼5% of type Ia supernovae observed in old stellar populations.

  14. Epigenetic Reprogramming of Muscle Progenitors: Inspiration for Clinical Therapies

    Directory of Open Access Journals (Sweden)

    Silvia Consalvi

    2016-01-01

    Full Text Available In the context of regenerative medicine, based on the potential of stem cells to restore diseased tissues, epigenetics is becoming a pivotal area of interest. Therapeutic interventions that promote tissue and organ regeneration have as primary objective the selective control of gene expression in adult stem cells. This requires a deep understanding of the epigenetic mechanisms controlling transcriptional programs in tissue progenitors. This review attempts to elucidate the principle epigenetic regulations responsible of stem cells differentiation. In particular we focus on the current understanding of the epigenetic networks that regulate differentiation of muscle progenitors by the concerted action of chromatin-modifying enzymes and noncoding RNAs. The novel exciting role of exosome-bound microRNA in mediating epigenetic information transfer is also discussed. Finally we show an overview of the epigenetic strategies and therapies that aim to potentiate muscle regeneration and counteract the progression of Duchenne Muscular Dystrophy (DMD.

  15. Glial progenitor cell-based treatment of the childhood leukodystrophies

    DEFF Research Database (Denmark)

    Osório, M. Joana; Goldman, Steven A.

    2016-01-01

    stem cell-derived human neural or glial progenitor cells may comprise a promising strategy for both structural remyelination and metabolic rescue. A broad variety of pediatric white matter disorders, including the primary hypomyelinating disorders, the lysosomal storage disorders, and the broader group...... genetic editing of pluripotent stem cells. Yet these challenges notwithstanding, the promise of glial progenitor cell-based treatment of the childhood myelin disorders offers hope to the many victims of this otherwise largely untreatable class of disease....... and astrocytes are the major affected cell populations, and are either structurally impaired or metabolically compromised through cell-intrinsic pathology, or are the victims of mis-accumulated toxic byproducts of metabolic derangement. In either case, glial cell replacement using implanted tissue or pluripotent...

  16. Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination

    Directory of Open Access Journals (Sweden)

    Alerie Guzman De La Fuente

    2017-08-01

    Full Text Available The role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs rapidly develop. During remyelination, mature oligodendrocytes were found in close proximity to PCs. In Pdgfbret/ret mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC differentiation was delayed, although remyelination proceeded to completion. PC-conditioned medium accelerated and enhanced OPC differentiation in vitro and increased the rate of remyelination in an ex vivo cerebellar slice model of demyelination. We identified Lama2 as a PC-derived factor that promotes OPC differentiation. Thus, the functional role of PCs is not restricted to vascular homeostasis but includes the modulation of adult CNS progenitor cells involved in regeneration.

  17. Is black-hole ringdown a memory of its progenitor?

    Science.gov (United States)

    Kamaretsos, Ioannis; Hannam, Mark; Sathyaprakash, B S

    2012-10-05

    We perform an extensive numerical study of coalescing black-hole binaries to understand the gravitational-wave spectrum of quasinormal modes excited in the merged black hole. Remarkably, we find that the masses and spins of the progenitor are clearly encoded in the mode spectrum of the ringdown signal. Some of the mode amplitudes carry the signature of the binary's mass ratio, while others depend critically on the spins. Simulations of precessing binaries suggest that our results carry over to generic systems. Using Bayesian inference, we demonstrate that it is possible to accurately measure the mass ratio and a proper combination of spins even when the binary is itself invisible to a detector. Using a mapping of the binary masses and spins to the final black-hole spin allows us to further extract the spin components of the progenitor. Our results could have tremendous implications for gravitational astronomy by facilitating novel tests of general relativity using merging black holes.

  18. THE POPULATION OF HELIUM-MERGER PROGENITORS: OBSERVATIONAL PREDICTIONS

    International Nuclear Information System (INIS)

    Fryer, Chris L.; Belczynski, Krzysztof; Bulik, Tomasz; Berger, Edo; Thöne, Christina; Ellinger, Carola

    2013-01-01

    The helium-merger gamma-ray burst (GRB) progenitor is produced by the rapid accretion onto a compact remnant (neutron star or black hole) when it undergoes a common envelope inspiral with its companion's helium core. This merger phase produces a very distinct environment around these outbursts and recent observations suggest that, in some cases, we are detecting the signatures of the past merger in the GRB afterglow. These observations allow us, for the first time, to study the specific features of the helium-merger progenitor. In this paper, we couple population synthesis calculations to our current understanding of GRB engines and common envelope evolution to make observational predictions for the helium-merger GRB population. Many mergers do not produce GRB outbursts and we discuss the implications of these mergers with the broader population of astrophysical transients.

  19. Progenitor cell populations in the periodontal ligament of mice

    International Nuclear Information System (INIS)

    McCulloch, C.A.

    1985-01-01

    Stem cells in a variety of renewal tissues exhibit a slow rate of cell proliferation. The periodontal ligament of mouse molars was examined for the presence of slowly cycling progenitor cells to provide evidence for the existence of stem cells in this tissue. A pulse injection of 3 H-thymidine was administered and mice were sacrificed between 1 hour and 14 days after injection. Analysis of radioautographs using percentage of labeled cells and grain counts demonstrated that a population of label-retaining cells within 10 micron of blood vessels traversed the cell cycle more slowly than proliferating cells located greater than 10 micron from blood vessels. These data suggest that there is a slowly dividing population of progenitor cells in paravascular sites in mouse molar periodontal ligament which may be stem cells

  20. In vitro pancreas organogenesis from dispersed mouse embryonic progenitors

    DEFF Research Database (Denmark)

    Greggio, Chiara; De Franceschi, Filippo; Figueiredo-Larsen, Evan Manuel

    2014-01-01

    The pancreas is an essential organ that regulates glucose homeostasis and secretes digestive enzymes. Research on pancreas embryogenesis has led to the development of protocols to produce pancreatic cells from stem cells (1). The whole embryonic organ can be cultured at multiple stages...... expanding progenitors and differentiate into endocrine, acinar and ductal cells and which spontaneously self-organize to resemble the embryonic pancreas. We show here that the in vitro process recapitulates many aspects of natural pancreas development. This culture system is suitable to investigate how...... cells cooperate to form an organ by reducing its initial complexity to few progenitors. It is a model that reproduces the 3D architecture of the pancreas and that is therefore useful to study morphogenesis, including polarization of epithelial structures and branching. It is also appropriate to assess...