The matrix composition of the cornea is critical to its function as a transparent barrier in the visual pathway. In addition to collagen type I, the major corneal collagen, up to 20 percent of the collagen of the cornea is composed of collage V, a minor constituent in other tissues. This project tests the hypothesis that type V collagen regulates corneal organization, specifically, the assembly and diameter of heterotypic collagen I/V fibrils. It employs the pN/pN mouse which carries a targeted mutation in collagen a2(V). Previous esults showing abnormal corneal stroma development in both homozygote and heterozygote mutants are consistent with this hypothesis.
The Specific Aims are to test the following predictions of the hypothesis: 1. The diameter of corneal collagen fibrils depends upon the inclusion or exclusion of type V collagen in heterotypic fibrils of the cornea. 2. A mutation of collagen V alters its transit through the synthetic and secretory pathway. 3. Collagen V and Collagen I/V heterotype fibrils bind to keratocyte cell surface receptors in ligand specific fashions. 4. Mutant type V collagen alters the functional integrity of the corneal stroma. The proposed experiments will provide fundamental information about the cellular mechanisms of cell/matrix interaction and about the role of type V collagen in corneal stroma development and in remodeling such as occurs during wound healing.
