This project seeks to detrmine whether the regulation of lens fiber differentiation and maturation is associated with alterations in the plasma membrane. The composition, biosynthesis, and metabolism of lens lipids have been investigated using embryonic and adult chicken lenses, and cultured lens epithelial cells derived from the Nakano mouse. The rate of degradation of the membrane phospholipid, phosphatidylinositol, has been shown to be tightly coupled to the rate of lens epithelial cell division and to cease when the epithelial cells differentiate to form lens fibers. Cultured lens epithelial cells and cultured fibroblasts have been shown to possess a mechanism for the rapid, transient gradation of phosphatidylinositol, which is independent of phospholipase C or phospholipase A2. A similar pathway may play a role in the differentiation of lens epithelial cells into lens fibers. Since phosphatidylinositol is rich in arachidonic acid, a precursor of prostaglandins and leukotrienes, the metabolities of arachidonic acid produced by lens epithelial cells are being characterized in an effort to understand the physiological role of phosphatidylinositol degradation. Analysis of the archadonic acid metabolities of cultured lens epithelial cells of several species revealed the presence of both cyclo-oxygenase and lipoxygenase products, including prostagladins E2 and F2Alpha, and leukotrienes. All lens epithelial cell types examined synthesized products of the 5-lipoxygenase pathway of arachidonic acid metabolism. One product of this pathway, 5-hydroxytetraenoic acid, was weakly mitogenic when added to cultured lens epithelial cells in the absence of serum or growth factors. Alterations in phosphatidylinositol metabolism and in the production of arachidonic acid metabolites are bieng correlated with the action of growth factors in regulating cell division and differentiation.
