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M.S. Balda, J. Greenwood, P. Adamson, K. Matter; Differentiation of Retinal Pigment Epithelium: The Role of the Tight Junction Associated Transcription Factor ZONAB . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2278.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The retinal pigment epithelium (RPE) is located between the neural retina and the vascular choroid and forms the outer blood-retinal barrier. One of the key features of a differentiated RPE is to establish tight junctions, the cell-cell junctions that regulate selective diffusion of solutes along the paracellular space and that are also involved in the control of cell proliferation and gene expression. We recently identified ZONAB, a Y-box transcription factor that interacts with the tight junction protein ZO-1. ZO-1 and ZONAB functionally interact to regulate the expression of the co-growth factor receptor erbB-2 and cell cycle progression. Our working hypothesis is that ZO-1 and ZONAB regulate gene expression and, thereby, epithelial cell proliferation and differentiation in a cell-density dependent manner. Methods: We have generated stably transfected ARPE-19 cell lines that overexpress either ZO-1 or ZONAB. These cell lines were then used to study junction assembly as well as cytoskeletal architecture and markers by fluorescence microscopy as well as cell and molecular biological assays to assess RPE differentiation. Results: In the RPE cell line ARPE-19, overexpression of ZONAB causes dedifferentiation manifested by disorganisation of cell-cell junctional and cytoskeletal proteins such as ZO-1, beta-catenin, actin and alpha-smooth muscle actin. Conclusions: These results indicate that ZONAB signal transduction pathway(s) regulate the differentiation of retinal pigment epithelium and suggest that manipulation of ZONAB function is a promising strategy to manipulate RPE proliferation and differentiation.
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