Molecular mechanisms of corneal infection

Acanthamoeba parasites produce sight-threatening corneal infection, especially in contact lens wearers. Adhesion of the organism to the surface of the cornea is clearly a critical first step in the pathogenesis of infection. Our goals in the recent past have been to delineate the mechanism by which the amoebae adhere to the surface of the cornea and cause cytolysis and necrosis of host tissues. We have demonstrated that the amoebae adhere to the surface of corneal epithelium via a mannose binding protein and that subsequent to the adhesion, amoebae secrete a cytotoxic metalloproteinase. We have found novel methods to inhibit the adhesion of amoebae to host cells and to inhibit the parasite's ability to produce cytotoxic proteinases. Our goals are to find a means to identify individuals who are at risk of developing the infection by testing their tear samples and to provide them with rationally designed strategies to protect against the infection. These studies also contribute significantly to the core mechanisms of cell biology.

Molecular mechanisms of corneal epithelial wound healing

In recent years, we have been investigating the role of carbohydrate-binding proteins, galectins, in corneal epithelial sheet migration, a key event in corneal epithelial wound healing. Studies from my laboratory have suggested that specifically galectin-3 plays a role in events which mediate corneal epithelial sheet migration. We are currently investigating the mechanism by which galectin-3 mediates corenal epithelial sheet migration and wound closure. Our goal is to deleniate specific signal transduction pathways which may be modulated by galectins. We hope that these studies will contribute to a better understanding of the molecular mechanisms that mediate migration of the corneal epithelial sheet over the wound surface and will ultimately help find novel methods to promote corneal epithelial wound closure in patients suffering from nonhealing epithelial defects.

In addition, we are investigating the mechanisms that mediate corneal epithelial cell-cell adhesion. Our recent studies have demonstrated that specifically, a corneal epithelial cell surface glycoprotein carrying a carbohydrate antigen, LewisX, plays a key role in corneal epithelial cell-cell adhesion. This glycoprotein also appears to play a role in corneal epithelial cell differentiation. The synthesis of the Lewis-X oligosaccharides is mediated by alpha(1,3)fucosyltransferases. In this project, our goals are to characterize the core protein of the LewisX-glycoprotein and fucosyltransferases of corneal epithelium with respect to their function in diseases processes of the cornea.

Recent Developments