Our current research focuses on the development and regulation of RPE tight junctions. Tight junctions are an integral part of any blood-tissue barrier, because they regulate diffusion across the paracellular spaces of an epithelial monolayer. Tight junctions form a network of anastomosing strands that encircles each cell and binds it to its neighbors in the monolayer. In the photo above, the RPE monolayer is viewed en face with the tight junctions illuminated by fluorescent tags for the tight junction protein, ZO-1, and the subadjacent circumferential band of actin. During embryonic development, the RPE and junctional functions develop gradually.
Development is coordinated with the neural retina by two-way communications between the tissues .
We continue to document changes in the expression of tight junctional proteins during development and wish to understand how the neural retina regulates the composition and function of the junction. We partially characterized the retinal factors that regulate the permeability of tight junctions, and found at least two factors that act at different stages of development. Our interest is in how these factors regulate two modes of tight junction function that were revealed by our culture model. We recently cloned the avian form of the tight junction protein, ZO-2 . Some regions of this protein are remarkably conserved among species, and we are using this insight to create dominant negative mutations for use in our culture system.