During the past grant period the PI has shown that the normal differentiation of the tissues of the anterior segment of the eye is regulated by the lens. Removal of the lens prevent the normal differentiation of the ciliary epithelium, cornea, iris and trabecular meshwork. Transplantation of the lens to the posterior of the optic cup causes cells that would have become retina to differentiate into ciliary epithelium and iris. Transplantation of a second lens to the anterior of the optic cup induces the formation of a second anterior chamber, iris and ciliary epithelium with ciliary folds. in the current proposal he will complete experiments demonstrating the forces responsible for the formation of the ciliary folds, determine the stages at which the lens produces the factor(s) necessary for organizing the anterior segment, identify the factors produced by the lens required for its organizing activity, determine the role of the lens in regulating the expression of mRNAs for several transcription factors known or believed to be important in the development of the anterior segment and identify cis-acting elements and transcription factors involved in regulating the synthesis of collagen IX, a major protein product of the ciliary epithelium. These studies should reveal the regulatory network required for the normal development of the tissues of the anterior segment. It is also likely that this work will identify candidate genes and the regulatory network involved in hereditary anterior segment dysgenesis and congenitalgalucoma.
