This project aims to understand the mechanism by which growth factors (GF) and their signal mediators control lens epithelial and fiber cell formation and metabolism, in order to characterize the mitogenesis, differentiation and growth processes that occur during lens development, aging and cataract formation. They have characterized an important signal transduction enzyme, phosphatidylinositol-3 kinase (PI-3K), that plays a vital role in cell proliferation, differentiation and in prevention of apoptosis. They have also found that treatment of lens epithelial cell with insulin and IGF-1 resulted in the tyrosine phosphorylation of the regulatory subunit of PI-3K and activation of the enzyme. This enzyme and some of its known downstream components are present in fully differentiated fiber cells. In addition, the protein tyrosine phosphorylation process, which is important in PI-3K mediated signal transduction, was found to be affected in lenses that developed cataract. They hypothesized that (1) activation of GF receptor mediated intracellular signaling pathways, particularly the products of PI-3K and of other downstream enzymes, regulates the metabolism of individual lens cells. (2) Disturbances in protein tyrosine phosphorylation and the PI-3K signaling cascade could be a contributing factor in cataract formation. Identification of pathway components will be accomplished by immunoprecipitation and Western immunoblotting. Lens organ culture will also be employed to induce cataract-related changes with PI-3K inhibitors.
| Chandrasekher, Gudiseva; Sailaja, Dasetty (2004) Alterations in lens protein tyrosine phosphorylation and phosphatidylinositol 3-kinase signaling during selenite cataract formation. Curr Eye Res 28:135-44 |
| Chandrasekher, Gudiseva; Sailaja, Dasetty (2004) Phosphatidylinositol 3-kinase (PI-3K)/Akt but not PI-3K/p70 S6 kinase signaling mediates IGF-1-promoted lens epithelial cell survival. Invest Ophthalmol Vis Sci 45:3577-88 |
| Chandrasekher, Gudiseva; Sailaja, Dasetty (2003) Differential activation of phosphatidylinositol 3-kinase signaling during proliferation and differentiation of lens epithelial cells. Invest Ophthalmol Vis Sci 44:4400-11 |
