Collagens and retinal Müller cells in healthy and diseased vitreoretinal interface: the regulatory role of extracellular matrix

Shao Bu

    Research output: ThesisThesis fully internal (DIV)

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    Abstract

    Collagens and Retinal Müller Cells in Healthy and Diseased Vitreoretinal Interface ---- The regulatory role of extracellular matrix
    The vitreoretinal interface encompasses the cortical vitreous, inner limiting membrane and the endfeet of retinal Müller cells. The remodelling of the ECM at the vitreoretinal interface during ageing and fibrotic processes may regulate the pathogenesis of certain vitreoretinal diseases.
    1. The ultrastructural localization of type II, IV and VI collagens in the healthy adult vitreoretinal interface was studied by transmission electron microscopy using immunogold labeling.
    2. Epiretinal membranes (ERMs) from idiopathic macular hole and idiopathic ERM (iERM) contain type I, III and V collagens. In addition, type VI collagen was not observed in ERM associated with idiopathic MH but it was found in idiopathic ERM. A double-labeling immunohistochemical study suggested that retinal Müller cells are actively involved in the formation of ERM by proliferation, migration and transdifferentiation. An in vitro cell culture study using a human retinal Müller cell line showed that transforming growth factor β (TGF-β) can induce an up-regulation of α-smooth muscle actin (α-SMA) stress fibers and possibly regulates the expression of collagens in Müller cells.
    3. Tissue stiffness promotes the up-regulation of α-SMA stress fibers in retinal Müller cells in response to TGF-β. This suggests that retinal Müller cells that come into contact with a stiffer extracellular matrix such as that resulting from ageing or fibrotic processes, may be more susceptible to TGF-β stimulation.
    In summary, the understanding of molecular mechanisms and mechanical cues underlying the pro-fibrotic effects of ECM components, permits the construction of a plausible sequence of events that lead to the development of iERM.
    Translated title of the contributioncollagenen en retinale Müller cellen in de gezonde en pathologisch veranderde vitreoretinale grenslaag: de regulatoire rol van de extracellulaire matrix
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Hooymans, Anneke, Supervisor
    • Los, Leonie, Co-supervisor
    • Kuijer, Roelof, Co-supervisor
    Award date4-Mar-2015
    Place of Publication[S.l.]
    Publisher
    Print ISBNs978-90-367-7692-9
    Publication statusPublished - 2015

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