Corneal transparency is dependent upon the interaction of several unique extracellular matrices that are synthesized and deposited by both the stromal fibroblasts and the endothelial and epithelial cell layers. Bowmans's membrane is an acellular extracellular matrix at the interface between the corneal epithelium and the underlying stroma. In this position, it links two dissimilar extracellular matrices, the epithelial basement membrane and the stroma proper. The transition zones between these two flanking matrices and Bowman's membrane, where molecular composition and extracellular organization change, are termed interfacial matrices. Physical properties of Bowman's membrane and these associated interfacial matrices, such as the exceptionally narrow collagen fibril diameter, organization and elevated stability, suggest these are unique regions in the cornea. The hypothesis ito be tested that Bowman's membrane and adjacent interfacial matrices are critical for maintaining the structural integrity of this region of the cornea as well as for epithelial attachment and function. The structure and composition of this region will be characterized morphologically and immunochemically. The PI also hypothesizes that the integrity of these regions is maintained by the assembly of components in unusual, if not unique configurations. Type XVII collagen is situated at the Bowman's-stroma boundary and is a strong candidate for mediating attachment of Bowman's membrane to the stroma. The function of these candidate molecules will be elucidated. The strategy involves the assembly of dominant-negative constructs designed to reduce the endogenous levels of these collagens. Constructs will be delivered in vivo using retroviral particles. The effects of modulating these candidate molecules will be determined using molecular genetic, biochemical, immunochemical and morphological approaches. He will analyze the structure and composition of the matrices assembled in infected regions,the enhanced stability of these regions and the attachment to the flanking extracellular matrices, the epithelial basement membrane and the stroma. Bowman's membrane and associated interfacial matrices provide the substrate upon both the epithelial basement membrane remodeling, corneal defense and repair that must operate continually to maintain visual acuity.
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