Past studies by the applicant have shown that neolacto-glycosphingolipids (neolacto-GSLs) of the corneal epithelium are among the key molecules that mediate corneal epithelial wound closure in vitro. The current project proposes to identify the mechanism by which the neolacto-GSLs mediate corneal epithelial sheet migration in vitro using a rabbit model to determine whether the neolacto-GSLs of corneal epithelium mediate re-epithelialization of wounds in vivo. Using cell-substratum adhesion assays, assays involving adhesion of integrin-liposomes to various extracellular matrix molecules and Western blot analysis of phosphorylated proteins, the applicant will attempt to establish whether the corneal epithelial cell surface neolacto-GSLs modulate: cell-substratum interactions (aim 1), the function of beta1 integrin receptors (aim 2) and tyrosine phosphorylation-mediated signalling pathways (aim 3). Using in vitro corneal epithelial wound healing assays, the applicant will determine whether the neolacto-GSLs promote corneal epithelial wound closure by interacting with one or more endogenous lectins in the cell substratum (aim 4). To evaluate the impact of the in vitro findings to healing in vivo (aim 5), the applicant will determine whether the exogenous neolacto-GSLs promote healing of the scrape and superficial keratectomy wounds of rabbit corneas in vivo.
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