Abnormal epithelial differentiation is the hallmark of two major categories of ocular surface disorders. In the first, the conjunctival epithelium exhibits squamous metaplasia, with goblet cell loss, cell enlargement and keratinization, with accompanying tear film instability and corneal changes that result in reduced vision. In the second, the corneal epithelium is replaced by conjunctival epithelium (""""""""conjunctivalization""""""""), with accompanying surface irregularity and vascularization that result in reduced vision. We plan further experiments to elucidate the role of retinoids in modulating epithelial differentiation, with the goal of better managing these categories of ocular surface disorders. We plan to: (1) Study the modulation of conjunctival epithelial differentiation by retinoids in vitro, using our single-cell clonal growth model. Phenotypic expression of each colony derived from various stages of epithelial differentiation will be determined by biochemical and immunohistochemical analyses using cell-type specific monoclonal antibodies (MNABs). (2) Investigate molecular interactions between mucin and apical membrane proteins using MNABs approaches. The binding studies will be conducted with in situ and in vitro. (3) Study the use of photothrombosis for occlusion of corneal new vessels in inducing transdifferentiation of a conjunctiva-like epithelium on the cornea into a cornea-like epithelium. (4) Explore the potential of limbal epithelial cells in corneal re-surfacing and their role as a barrier to conjunctival migration.
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