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  1. Article ; Online: Mechanobiological implications of age-related remodelling in the outer retina.

    Piskova, Teodora / Kozyrina, Aleksandra N / Di Russo, Jacopo

    Biomaterials advances

    2023  Volume 147, Page(s) 213343

    Abstract: The outer retina consists of the light-sensitive photoreceptors, the pigmented epithelium, and the choroid, which interact in a complex manner to sustain homeostasis. The organisation and function of these cellular layers are mediated by the ... ...

    Abstract The outer retina consists of the light-sensitive photoreceptors, the pigmented epithelium, and the choroid, which interact in a complex manner to sustain homeostasis. The organisation and function of these cellular layers are mediated by the extracellular matrix compartment named Bruch's membrane, situated between the retinal epithelium and the choroid. Like many tissues, the retina experiences age-related structural and metabolic changes, which are relevant for understanding major blinding diseases of the elderly, such as age-related macular degeneration. Compared with other tissues, the retina mainly comprises postmitotic cells, making it less able to maintain its mechanical homeostasis over the years functionally. Aspects of retinal ageing, like the structural and morphometric changes of the pigment epithelium and the heterogenous remodelling of the Bruch's membrane, imply changes in tissue mechanics and may affect functional integrity. In recent years, findings in the field of mechanobiology and bioengineering highlighted the importance of mechanical changes in tissues for understanding physiological and pathological processes. Here, we review the current knowledge of age-related changes in the outer retina from a mechanobiological perspective, aiming to generate food for thought for future mechanobiology studies in the outer retina.
    MeSH term(s) Humans ; Aged ; Pigment Epithelium of Eye/metabolism ; Pigment Epithelium of Eye/pathology ; Retina/metabolism ; Retina/pathology ; Choroid/metabolism ; Choroid/pathology ; Bruch Membrane/metabolism ; Bruch Membrane/pathology ; Macular Degeneration/metabolism ; Macular Degeneration/pathology
    Language English
    Publishing date 2023-02-15
    Publishing country Netherlands
    Document type Review ; Journal Article
    ISSN 2772-9508
    ISSN (online) 2772-9508
    DOI 10.1016/j.bioadv.2023.213343
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Mechanobiology of Epithelia From the Perspective of Extracellular Matrix Heterogeneity.

    Kozyrina, Aleksandra N / Piskova, Teodora / Di Russo, Jacopo

    Frontiers in bioengineering and biotechnology

    2020  Volume 8, Page(s) 596599

    Abstract: Understanding the complexity of the extracellular matrix (ECM) and its variability is a necessary step on the way to engineering functional (bio)materials that serve their respective purposes while relying on cell adhesion. Upon adhesion, cells receive ... ...

    Abstract Understanding the complexity of the extracellular matrix (ECM) and its variability is a necessary step on the way to engineering functional (bio)materials that serve their respective purposes while relying on cell adhesion. Upon adhesion, cells receive messages which contain both biochemical and mechanical information. The main focus of mechanobiology lies in investigating the role of this mechanical coordination in regulating cellular behavior. In recent years, this focus has been additionally shifted toward cell collectives and the understanding of their behavior as a whole mechanical continuum. Collective cell phenomena very much apply to epithelia which are either simple cell-sheets or more complex three-dimensional structures. Researchers have been mostly using the organization of monolayers to observe their collective behavior in well-defined experimental setups
    Language English
    Publishing date 2020-11-20
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2719493-0
    ISSN 2296-4185
    ISSN 2296-4185
    DOI 10.3389/fbioe.2020.596599
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Combining Image Restoration and Traction Force Microscopy to Study Extracellular Matrix-Dependent Keratin Filament Network Plasticity.

    Yoon, Sungjun / Windoffer, Reinhard / Kozyrina, Aleksandra N / Piskova, Teodora / Di Russo, Jacopo / Leube, Rudolf E

    Frontiers in cell and developmental biology

    2022  Volume 10, Page(s) 901038

    Abstract: Keratin intermediate filaments are dynamic cytoskeletal components that are responsible for tuning the mechanical properties of epithelial tissues. Although it is known that keratin filaments (KFs) are able to sense and respond to changes in the ... ...

    Abstract Keratin intermediate filaments are dynamic cytoskeletal components that are responsible for tuning the mechanical properties of epithelial tissues. Although it is known that keratin filaments (KFs) are able to sense and respond to changes in the physicochemical properties of the local niche, a direct correlation of the dynamic three-dimensional network structure at the single filament level with the microenvironment has not been possible. Using conventional approaches, we find that keratin flow rates are dependent on extracellular matrix (ECM) composition but are unable to resolve KF network organization at the single filament level in relation to force patterns. We therefore developed a novel method that combines a machine learning-based image restoration technique and traction force microscopy to decipher the fine details of KF network properties in living cells grown on defined ECM patterns. Our approach utilizes Content-Aware Image Restoration (CARE) to enhance the temporal resolution of confocal fluorescence microscopy by at least five fold while preserving the spatial resolution required for accurate extraction of KF network structure at the single KF/KF bundle level. The restored images are used to segment the KF network, allowing numerical analyses of its local properties. We show that these tools can be used to study the impact of ECM composition and local mechanical perturbations on KF network properties and corresponding traction force patterns in size-controlled keratinocyte assemblies. We were thus able to detect increased curvature but not length of KFs on laminin-322 versus fibronectin. Photoablation of single cells in microprinted circular quadruplets revealed surprisingly little but still significant changes in KF segment length and curvature that were paralleled by an overall reduction in traction forces without affecting global network orientation in the modified cell groups irrespective of the ECM coating. Single cell analyses furthermore revealed differential responses to the photoablation that were less pronounced on laminin-332 than on fibronectin. The obtained results illustrate the feasibility of combining multiple techniques for multimodal monitoring and thereby provide, for the first time, a direct comparison between the changes in KF network organization at the single filament level and local force distribution in defined paradigms.
    Language English
    Publishing date 2022-05-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2022.901038
    Database MEDical Literature Analysis and Retrieval System OnLINE

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