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  • 1
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    Correlation between redefined optical coherence tomography parameters and best-corrected visual acuity in non-resolving central serous chorioretinopathy treated with half-dose photodynamic therapy
    Public Library of Science (PLoS) ; 2018
    In:  PLOS ONE Vol. 13, No. 8 ( 2018-8-24), p. e0202549-
    Details
    In: PLOS ONE, Public Library of Science (PLoS), Vol. 13, No. 8 ( 2018-8-24), p. e0202549-
    Type of Medium: Online Resource
    ISSN: 1932-6203
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.1371/journal.pone.0202549
    DOI: 10.1371/journal.pone.0202549.g001
    DOI: 10.1371/journal.pone.0202549.g002
    DOI: 10.1371/journal.pone.0202549.g003
    DOI: 10.1371/journal.pone.0202549.g004
    DOI: 10.1371/journal.pone.0202549.t001
    DOI: 10.1371/journal.pone.0202549.t002
    DOI: 10.1371/journal.pone.0202549.s001
    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2018
    detail.hit.zdb_id: 2267670-3
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  • 2
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    Computer-assisted photoreceptor assessment on Heidelberg Engineering Spectralis™ High Magnification Module™ images
    Springer Science and Business Media LLC ; 2021
    In:  Graefe's Archive for Clinical and Experimental Ophthalmology Vol. 259, No. 11 ( 2021-11), p. 3311-3320
    Details
    In: Graefe's Archive for Clinical and Experimental Ophthalmology, Springer Science and Business Media LLC, Vol. 259, No. 11 ( 2021-11), p. 3311-3320
    Abstract: To evaluate reliability and repeatability of computer-assisted measurements of cone photoreceptor metrics on Heidelberg Engineering Spectralis™ High Magnification Module (HMM™) Automatic Real-time Tracking (ART™) images. Methods We analyzed HMM™ images in three separate study arms. Computer-assisted cone identification software was validated using an open-access adaptive optics (AO) dataset. We compared results of the first arm to data from AO and histology. We evaluated intersession repeatability of our computer-assisted cone analysis in the second arm. We assessed the capability of HMM™ to visualize cones in the presence of pathology in the third arm. Results We included 10 healthy subjects in the first arm of our study, 5 additional healthy participants in the second arm and 5 patients in the third arm. In total, we analyzed 225 regions of interest on HMM™ images. We were able to automatically identify cone photoreceptors and assess corresponding metrics at all eccentricities between 2 and 9° from the fovea. Cone density significantly declined with increasing eccentricity ( p  = 4.890E-26, Friedman test). With increasing eccentricity, we found a significant increase in intercell distance ( p  = 2.196E-25, Friedman test) and nearest neighbor distance ( p  = 1.997E-25, Friedman test). Cone hexagonality ranged between 71 and 85%. We found excellent automated intersession repeatability of cone density counts and spacing measurements. In pathology, we were also able to repeatedly visualize photoreceptors. Conclusion Computer-assisted cone photoreceptor analysis on Spectralis™ HMM™ images is feasible, and most cone metrics show excellent repeatability. HMM™ imaging may be useful for photoreceptor analysis as progression marker in outer retinal disease.
    Type of Medium: Online Resource
    ISSN: 0721-832X , 1435-702X
    URL: Article
    DOI: 10.1007/s00417-021-05326-6
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1459159-5
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  • 3
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    Towards seeing the visual impairments in Parkinson’s disease: protocol for a multicentre observational, cross-sectional study
    Springer Science and Business Media LLC ; 2019
    In:  BMC Neurology Vol. 19, No. 1 ( 2019-12)
    Details
    In: BMC Neurology, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2019-12)
    Type of Medium: Online Resource
    ISSN: 1471-2377
    URL: Article
    DOI: 10.1186/s12883-019-1365-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2041347-6
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  • 4
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    Reversal of Hypoxia in Murine Atherosclerosis Prevents Necrotic Core Expansion by Enhancing Efferocytosis
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 34, No. 12 ( 2014-12), p. 2545-2553
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 34, No. 12 ( 2014-12), p. 2545-2553
    Abstract: Advanced murine and human plaques are hypoxic, but it remains unclear whether plaque hypoxia is causally related to atherogenesis. Here, we test the hypothesis that reversal of hypoxia in atherosclerotic plaques by breathing hyperoxic carbogen gas will prevent atherosclerosis. Approach and Results— Low-density lipoprotein receptor–deficient mice (LDLR -/- ) were fed a Western-type diet, exposed to carbogen (95% O 2 , 5% CO 2 ) or air, and the effect on plaque hypoxia, size, and phenotype was studied. First, the hypoxic marker pimonidazole was detected in murine LDLR -/- plaque macrophages from plaque initiation onwards. Second, the efficacy of breathing carbogen (90 minutes, single exposure) was studied. Compared with air, carbogen increased arterial blood pO 2 5-fold in LDLR -/- mice and reduced plaque hypoxia in advanced plaques of the aortic root (−32%) and arch (−84%). Finally, the effect of repeated carbogen exposure on progression of atherosclerosis was studied in LDLR -/- mice fed a Western-type diet for an initial 4 weeks, followed by 4 weeks of diet and carbogen or air (both 90 min/d). Carbogen reduced plaque hypoxia (−40%), necrotic core size (−37%), and TUNEL + (terminal uridine nick-end labeling positive) apoptotic cell content (−50%) and increased efferocytosis of apoptotic cells by cluster of differentiation 107b + (CD107b, MAC3) macrophages (+36%) in advanced plaques of the aortic root. Plaque size, plasma cholesterol, hematopoiesis, and systemic inflammation were unchanged. In vitro, hypoxia hampered efferocytosis by bone marrow–derived macrophages, which was dependent on the receptor Mer tyrosine kinase. Conclusions— Carbogen restored murine plaque oxygenation and prevented necrotic core expansion by enhancing efferocytosis, likely via Mer tyrosine kinase. Thus, plaque hypoxia is causally related to necrotic core expansion.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/ATVBAHA.114.304023
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 1494427-3
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  • 5
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    A Prospective, Comparative, Observational Study on Optical Coherence Tomography of the Anterior Eye Segment
    S. Karger AG ; 2013
    In:  Ophthalmologica Vol. 230, No. 4 ( 2013), p. 222-226
    Details
    In: Ophthalmologica, S. Karger AG, Vol. 230, No. 4 ( 2013), p. 222-226
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 We compared two commercially available spectral-domain optical coherence tomography (OCT) devices according to their capacity of imaging the anterior segment of the eye with the same detail and quality. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 A prospective, observational, single-visit study with individuals aged 18 years and older was conducted on two different OCT devices: the Spectralis™ OCT and the RTVue™ OCT. The resulting OCT images of both study devices of each study subject were compared and qualified by a single investigator according to the identification of corresponding structures and pathologies (primary endpoint) and the comparability of the clinical information given (secondary endpoint). 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 We included 28 eyes (28 patients) in our study, e.g. 8 normal eyes, 7 of subjects with corneal disease, 8 eyes with chamber angle pathology and 5 cases with pathology of the sclera. Of all anterior segment structures analyzed, 93.9% were identified by Spectralis™ OCT and 91.2% were detected by RTVue® OCT with a high positive correlation (r = 0.996; p 〈 0.0001) between the two devices. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 The majority of clinically relevant structures could be identified with both devices in all subjects. The Spectralis OCT tended to perform better in the illustration of deep anterior segment structures like the ciliary body and sclera.
    Type of Medium: Online Resource
    ISSN: 0030-3755 , 1423-0267
    URL: Article
    DOI: 10.1159/000354114
    RVK:
    XA 10000
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2013
    detail.hit.zdb_id: 1483531-9
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  • 6
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    Abstract 532: Periadventitial Adenoviral Ang-1/2 Gene Transfer Interferes with Atherosclerotic Plaque Progression and Angiogenesis in the Carotid Artery of LDLr -/- ApoB100/100 Mice
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 32, No. suppl_1 ( 2012-05)
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 32, No. suppl_1 ( 2012-05)
    Abstract: Accumulation of macrophages, red blood cells and lipids in atherosclerotic plaques is associated with plaque rupture. It has been shown that macrophages and erythrocytes can enter the plaque also via plaque microvasculature originating from the adventitia. Furthermore, it has been reported that in advanced or ruptured human coronary lesions the microvessel density is increased and these microvessels are leaky. The leaky phenotype is characterized by poor pericyte coverage and dysfunctional inter-endothelial junctions. As angiopoietins are involved in angiogenic growth and maturation, we hypothesized that periadventitial Ang-1 or Ang-2 gene transfer would reduce atherogenesis and affect microvasculature in mouse carotid artery. To study this, atherosclerosis was induced by placing a perivascular silastic collar around the carotid artery of LDLr -/- ApoB100/100 mice fed a high cholesterol (0,15 %) diet for 3 weeks. Simultaneous to surgery adenoviral gene transfer (5μl, 5 x 107 pfu/ml) of either Ang-1, Ang-2 or LacZ as a control was applied to the carotid artery (20 mice per group). After 1 or 5 weeks follow-up on high cholesterol diet mice were sacrificed. Plaque size and microvessel density were analyzed with morphometry software (Leica Qwin) using cross-sections stained with hematoxylin and eosin or CD31 respectively. Microvessel ultrastructure was studied using electron microscopy. Ang-2 gene transfer led to significantly smaller plaque area and plaque volume 5 weeks after collar placement compared to LacZ group (2,7 fold, p 〈 0,001 and 3,9 fold, p 〈 0,01 respectively). Also the microvessel density in intima, media and adventitia was lower in the Ang-2 group compared to LacZ (4,5 fold, p 〈 0,05; 7,5 fold p 〈 0,05 and 11,8 fold p 〈 0,05 respectively). Ang-1 gene transfer led to a non-significant trend towards smaller lesions and lower microvessel density compared to LacZ gene transfer. Plaque phenotype was quite fibrous in all groups at 5 weeks, although lesions in Ang-2 group were most human atheroma-like. Electron microscopy showed intact pericyte coverage and endothelial junctions of microvessels in all groups. Endothelial cell morphology after Ang-1 gene transfer showed less filopodia and cytoplasmic vacuoles compared to Ang-2 and LacZ, suggestive of a quiescent phenotype. In conclusion: Ang-2 over expression in mouse carotid arteries led to smaller plaque size and lower microvessel density, suggesting the involvement of angiopoietin signaling in angiogenesis of the atherosclerotic vessel wall.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/atvb.32.suppl_1.A532
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
    detail.hit.zdb_id: 1494427-3
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  • 7
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    Variable Clinical Spectrum of the Myocilin Gln368X Mutation in a Dutch Family with Primary Open Angle Glaucoma
    Informa UK Limited ; 2010
    In:  Current Eye Research Vol. 35, No. 1 ( 2010-01-01), p. 31-36
    Details
    In: Current Eye Research, Informa UK Limited, Vol. 35, No. 1 ( 2010-01-01), p. 31-36
    Type of Medium: Online Resource
    ISSN: 0271-3683 , 1460-2202
    URL: Article
    DOI: 10.3109/02713680903374182
    RVK:
    XA 10000
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2010
    detail.hit.zdb_id: 1483048-6
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  • 8
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    Deficiency of myeloid PHD proteins aggravates atherogenesis via macrophage apoptosis and paracrine fibrotic signalling
    Oxford University Press (OUP) ; 2022
    In:  Cardiovascular Research Vol. 118, No. 5 ( 2022-03-25), p. 1232-1246
    Details
    In: Cardiovascular Research, Oxford University Press (OUP), Vol. 118, No. 5 ( 2022-03-25), p. 1232-1246
    Abstract: Atherosclerotic plaque hypoxia is detrimental for macrophage function. Prolyl hydroxylases (PHDs) initiate cellular hypoxic responses, possibly influencing macrophage function in plaque hypoxia. Thus, we aimed to elucidate the role of myeloid PHDs in atherosclerosis. Methods and results Myeloid-specific PHD knockout (PHDko) mice were obtained via bone marrow transplantation (PHD1ko, PHD3ko) or conditional knockdown through lysozyme M-driven Cre recombinase (PHD2cko). Mice were fed high cholesterol diet for 6–12 weeks to induce atherosclerosis. Aortic root plaque size was significantly augmented 2.6-fold in PHD2cko, and 1.4-fold in PHD3ko compared to controls but was unchanged in PHD1ko mice. Macrophage apoptosis was promoted in PHD2cko and PHD3ko mice in vitro and in vivo, via the hypoxia-inducible factor (HIF) 1α/BNIP3 axis. Bulk and single-cell RNA data of PHD2cko bone marrow-derived macrophages (BMDMs) and plaque macrophages, respectively, showed enhanced HIF1α/BNIP3 signalling, which was validated in vitro by siRNA silencing. Human plaque BNIP3 mRNA was positively associated with plaque necrotic core size, suggesting similar pro-apoptotic effects in human. Furthermore, PHD2cko plaques displayed enhanced fibrosis, while macrophage collagen breakdown by matrix metalloproteinases, collagen production, and proliferation were unaltered. Instead, PHD2cko BMDMs enhanced fibroblast collagen secretion in a paracrine manner. In silico analysis of macrophage-fibroblast communication predicted SPP1 (osteopontin) signalling as regulator, which was corroborated by enhanced plaque SPP1 protein in vivo. Increased SPP1 mRNA expression upon PHD2cko was preferentially observed in foamy plaque macrophages expressing ‘triggering receptor expressed on myeloid cells-2’ (TREM2hi) evidenced by single-cell RNA, but not in neutrophils. This confirmed enhanced fibrotic signalling by PHD2cko macrophages to fibroblasts, in vitro as well as in vivo. Conclusion Myeloid PHD2cko and PHD3ko enhanced atherosclerotic plaque growth and macrophage apoptosis, while PHD2cko macrophages further activated collagen secretion by fibroblasts in vitro, likely via paracrine SPP1 signalling through TREM2hi macrophages.
    Type of Medium: Online Resource
    ISSN: 0008-6363 , 1755-3245
    URL: Article
    DOI: 10.1093/cvr/cvab152
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1499917-1
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  • 9
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    Multiple Hybridization Events Punctuate the Evolutionary Trajectory of Malassezia furfur
    American Society for Microbiology ; 2022
    In:  mBio Vol. 13, No. 2 ( 2022-04-26)
    Details
    In: mBio, American Society for Microbiology, Vol. 13, No. 2 ( 2022-04-26)
    Abstract: Malassezia species are important fungal skin commensals and are part of the normal microbiota of humans and other animals. However, under certain circumstances these fungi can also display a pathogenic behavior. For example, Malassezia furfur is a common commensal of human skin and yet is often responsible for skin disorders but also systemic infections. Comparative genomics analysis of M. furfur revealed that some isolates have a hybrid origin, similar to several other recently described hybrid fungal pathogens. Because hybrid species exhibit genomic plasticity that can impact phenotypes, we sought to elucidate the genomic evolution and phenotypic characteristics of M. furfur hybrids in comparison to their parental lineages. To this end, we performed a comparative genomics analysis between hybrid strains and their presumptive parental lineages and assessed phenotypic characteristics. Our results provide evidence that at least two distinct hybridization events occurred between the same parental lineages and that the parental strains may have originally been hybrids themselves. Analysis of the mating-type locus reveals that M. furfur has a pseudobipolar mating system and provides evidence that after sexual liaisons of mating compatible cells, hybridization involved cell-cell fusion leading to a diploid/aneuploid state. This study provides new insights into the evolutionary trajectory of M. furfur and contributes with valuable genomic resources for future pathogenicity studies. IMPORTANCE Malassezia furfur is a common commensal member of human/animal microbiota that is also associated with several pathogenic states. Recent studies report involvement of Malassezia species in Crohn’s disease, a type of inflammatory bowel disease, pancreatic cancer progression, and exacerbation of cystic fibrosis. A recent genomics analysis of M . furfur revealed the existence of hybrid isolates and identified their putative parental lineages. In this study, we explored the genomic and phenotypic features of these hybrids in comparison to their putative parental lineages. Our results revealed the existence of a pseudobipolar mating system in this species and showed evidence for the occurrence of multiple hybridization events in the evolutionary trajectory of M. furfur . These findings significantly advance our understanding of the evolution of this commensal microbe and are relevant for future studies exploring the role of hybridization in the adaptation to new niches or environments, including the emergence of pathogenicity.
    Type of Medium: Online Resource
    ISSN: 2150-7511
    URL: Article
    DOI: 10.1128/mbio.03853-21
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 2557172-2
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  • 10
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    Adventitial lymphatic capillary expansion impacts on plaque T cell accumulation in atherosclerosis
    Springer Science and Business Media LLC ; 2017
    In:  Scientific Reports Vol. 7, No. 1 ( 2017-03-28)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-03-28)
    Abstract: During plaque progression, inflammatory cells progressively accumulate in the adventitia, paralleled by an increased presence of leaky vasa vasorum. We here show that next to vasa vasorum, also the adventitial lymphatic capillary bed is expanding during plaque development in humans and mouse models of atherosclerosis. Furthermore, we investigated the role of lymphatics in atherosclerosis progression. Dissection of plaque draining lymph node and lymphatic vessel in atherosclerotic ApoE −/− mice aggravated plaque formation, which was accompanied by increased intimal and adventitial CD3 + T cell numbers. Likewise, inhibition of VEGF-C/D dependent lymphangiogenesis by AAV aided gene transfer of hVEGFR3-Ig fusion protein resulted in CD3 + T cell enrichment in plaque intima and adventitia. hVEGFR3-Ig gene transfer did not compromise adventitial lymphatic density, pointing to VEGF-C/D independent lymphangiogenesis. We were able to identify the CXCL12/CXCR4 axis, which has previously been shown to indirectly activate VEGFR3, as a likely pathway, in that its focal silencing attenuated lymphangiogenesis and augmented T cell presence. Taken together, our study not only shows profound, partly CXCL12/CXCR4 mediated, expansion of lymph capillaries in the adventitia of atherosclerotic plaque in humans and mice, but also is the first to attribute an important role of lymphatics in plaque T cell accumulation and development.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/srep45263
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2615211-3
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