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Collagens and retinal Müller cells in healthy and diseased vitreoretinal interface

The regulatory role of extracellular matrix
PhD ceremony:Mr S.C. (Shao) Bu
When:March 04, 2015
Supervisor:Prof. J.M.M. Hooymans
Co-supervisors:L.I. Los, Prof. R. Kuijer
Where:Academy building RUG
Faculty:Medical Sciences / UMCG

The vitreoretinal interface encompasses the cortical vitreous, inner limiting membrane and the end feet 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.

We studied the ultrastructural localization of type II, IV and VI collagens in the healthy adult vitreoretinal interface with transmission electron microscopy using immune gold labeling.

Epiretinal membranes (ERMs) from idiopathic macular hole and idiopathic ERM (iERM) were found to 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 immuno histochemical study suggested that retinal Müller cells are actively involved in the formation of ERM by proliferation, migration and trans differentiation. 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.

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.