The long-term objective is to understand the cell-biological and molecular bases of corneal (and other ocular) diseases so that loss of vision can be prevented. Previous work has indicated that wound healing/debridement proteolytic mechanisms can go awry to result in frank tissue damage. The plasminogen activator (PA)/plasmin system appears to have an important role in such lesions. This system will be studied as it relates to corneal epithelialization and stromal ulceration; to the regulation of corneal endothelial permeability and Fuchs' Dystrophy; and to a debridement system in the trabecular mesh and pigmentary glaucoma.
The specific aims of the application are to evaluate requirements for 1) fibronectin and 2) PA/plasmin in the spreading of corneal epithelial sheets over fibrin substrata (epithelialization); 3) to compare the PA/plasmin system in effective corenal wound healing (scrape injury) and in ineffective healing (alkali burn) in order to understand how epithelial wound healing goes awry in alkali burns; 4) to determine the relationship between the PA/plasmin system and cell surface (pericellular) adhesive proteins and the intracellular contractile system will regard to secretion of PA and collagenase; 5) to determine the relationship between PA/plasmin and corneal endothelial function with regard to Fuchs' Dystrophy; and 6) to explore the possibility that the PA/plasmin system is a debridement mechanism in the aqueous drainage channels and to determine if prigmentary glaucoma is associated with sustained, abnormally high plasminogen activator and collagenase activities. Understanding of the roles of the PA/plasmin system in the eye should contribute also to increased understanding of wound healing mechanisms outside the eye and to an understanding of tumor-invasive mechanisms. Methods of tissue culture on fibrin clots, protein chemistry, electromicroscopy and enzymatic, immunologic, and cytochemical techniques will be used to evaluate the requirement for fibronectin and the role of the PA/plasmin system in corneal epithelialization and in protease secretion by corneal epithelial, fibroblast and endothelial cells; and cells in the trabecular mesh.
| Hayashi, K; Berman, M; Smith, D et al. (1991) Pathogenesis of corneal epithelial defects: role of plasminogen activator. Curr Eye Res 10:381-98 |
| Johnson, M K; Gebhardt, B M; Berman, M B (1988) Appearance of collagenase in pneumolysin-treated corneal fibroblast cultures. Curr Eye Res 7:951-3 |
| Hayashi, K; Frangieh, G; Kenyon, K R et al. (1988) Plasminogen activator activity in vitamin A-deficient rat corneas. Invest Ophthalmol Vis Sci 29:1810-9 |
