Development of the cornea is a complex, poorly understood process. A thorough examination of the components of the cornea is essential for understanding human corneal defects, such as macular corneal dystrophy. The recent isolation of a major component of the cornea, lumican, from the mouse provides an ideal system in which to monitor corneal development. Lumican is hypothesized to play a role in corneal transparency and collagen fibrillogenesis. The isolation of lumican from the mouse provides the opportunity to manipulate lumican expression to examine the nature of its role in the cornea. In addition, the fortuitous discovery of the mouse eye blebs mutant offers the opportunity to examine the disturbance of normal lumican expression in a developmental defect affecting the cornea. The proposed research will test the role of lumican by examining its spatial and temporal expression pattern in normal and eye blebs mice with immunocytochemistry, followed by the elimination and overexpression of lumican using transgenic mice. The results of the overexpression and elimination of lumican will be monitored by immunocytochemistry and by monitoring the size, shape and transparency of the mouse cornea. In addition, interspecific backcrosses will be employed to determine the chromosomal relationship of eye blebs to lumican and other eye-related genes clustered on mouse chromosome 10.
