The anterior surface of the eye functions as a barrier to the external environment and protects the delicate structures of the anterior segment from injury. This protection is provided through the elaboration of the corneal, limbal, and conjunctival epithelia. Proteinases represent a class of molecules that are capable of influencing proliferation, differentiation and cells death; activities involved in epithelial homeostasis. The plasminogen activator (PA) cascade is one such proteinase system. Some of its components have been localized in ocular surface epithelia. Recent data have localized the proteinase inhibitor, plasminogen activator inhibitor type 2 (PAI-2) in human corneal, limbal, and conjunctival epithelia. Two pools of this inhibitor appear to be present within these epithelial cells, an active form and a cleaved (inactive) form. The hypothesis to be tested is that PAI-2, by interacting with an intracellular proteinase, serves to protect the cell from premature proteolytic damage or death.
The specific aims of this application are 1) to localize PAI-2 mRNA and antigen in human corneal and conjunctival epithelia in vivo and in vitro and determine the PAI-2 species present in vivo; 2) to identify the proteinase(s) that cleaves PAI-2 in human corneal epithelial cells; 3) to characterize biochemically PAI-2 and its interacting proteinase(s) in human conjunctival epithelial cells; and 4) to define the phenotype of corneal and conjunctival epithelial cells with increased and decreased levels of PAI-2. The long term goal is to understand the role that PAI-2 and its target proteinases play in ocular anterior segment epithelial homeostasis. These studies will serve as a baseline for future studies on the therapeutic use of PAI-2 in ophthalmology.
| Lang, Roland; Song, Peter I; Legat, Franz J et al. (2003) Human corneal epithelial cells express functional PAR-1 and PAR-2. Invest Ophthalmol Vis Sci 44:99-105 |
| Risse Marsh, Barbara C; Massaro-Giordano, Mina; Marshall, Christine M et al. (2002) Initiation and characterization of keratinocyte cultures from biopsies of normal human conjunctiva. Exp Eye Res 74:61-9 |
