Mazure, Ank; (1993) Cell-mediated contraction in three-dimensional collagen matrices in relation to proliferative vitreoretinopathy and wound contraction. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

Proliferative vitreoretinopathy (PVR) is the leading cause of failed retinal detachment surgery and is characterized by the formation of contractile cellular membranes on the surface of the retina resulting in redetachment. It was unknown from the available literature which of the cell types involved in PVR was responsible for the contraction. In the present study we have investigated the contractile capacities of three major cell types involved in PVR (fibroblasts, retinal pigment epithelium and retinal glial) using an in vitro contraction model based on a three-dimensional collagen matrix. Fibroblasts were shown to be the most effective, while glial cells were the least effective. Contrary to previous reports, fibronectin was found to be important in collagen matrix contraction. Morphological and immunohistochemical studies suggested that cell-to-matrix adhesion could be a key factor in the process of cell-mediated contraction. Thrombospondin and vitronectin were less prominent in glia-populated matrices and they may account for differences in contraction abilities between the three cell types. Collagen matrices are very suitable for drug evaluation studies. Sodium butyrate, a differentiating agent with anti-proliferative properties, had a modest inhibitory effect on cell-mediated contraction. Contraction in PVR has been likened to wound contraction elsewhere in the body. The two current theories on the mechanism of wound contraction are based on (1) the synchronized contraction of a syncytium of smooth muscle-like cells (myofibroblasts), and (2) the forces generated through the locomotion of individual cells. In our contraction model we have found evidence that collagen matrix contraction is the result of tractional structuring by individual cells in the process of locomotion. Our observations suggest that the concept that myofibroblasts are a cohesive, contractile unit may be incorrect. Myofibroblasts may represent a morphological modification associated with the generation of isometric tension. This modification can occur in many cell types. In wound healing, the two mechanisms of contraction probably represent separate phases in the process.

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