The role of cyclic AMP and of the hormone-sensitive adenylate cyclase system will be evaluated in development and aging of the lens, in the metabolic regulation of lens and in the diseased lens. Studies will include response to catecholamines, glucagon and prostaglandins. Tissue levels of adenylate cyclase, including hormone specificity and degree of hormone response, cyclic AMP, cyclic nucleotide phosphodiesterase, and cyclic AMP-dependent protein kinase, as well as levels in aqueous and vitreous humour of cyclic AMP and hormones will be determined. Possible regulation by cyclic AMP of transport of small molecules, glycolysis, phosphorylation of proteins and the synthesis of proteins (including collagen), RNA and DNA will also be studied. Consideration will be given to enzymatic and functional differences in various portions of the lens (anterior and posterior) superficial cell layers, as well as the interior. Developmental studies will emphasize the early postnatal period. Lens epithelial cells in culture will provide an additional system for study of regulation of this cell type by cyclic AMP. An important part of the investigation will be study of cyclic AMP formation and responsiveness in aged or immature lens of experimental animals, and in lens of animals with cataracts produced by sugar (e.g., galactose), alloxan, as well as in insulin-deficient but noncataractous lens of animals treated with alloxan plus phorizin. Cyclic AMP levels, rates of formation, hormonal responsiveness and effects of cyclic AMP will also be studied in both senile and diabetic cataractous lens of man.