The research activities in our laboratory branch into two separate categories, i.e.. (1) Basic Howe Laboratory Research and (2) Collaborative laboratory and/or clinical research. The present application deals exclusively with the first category. The overall objective of this proposal is the examination of metabolic pathways in the crystalline lens and their responses to various stresses. We hope to identify the major cataractogenic factors and seek means for reversing or eliminating such factors, and ultimately, to apply the information obtained to prevent or treat various types of human cataracts non-surgically. The areas of research include: (1) anaerobic glycolysis, (2) mitochondrial activity, (3) control of hexokinase activity, (4) oxidative stress in the lens, and (5) diabetic cataract prevention. Animal models are used initially and the information gathered is then extended to in vitro human lens studies. While not within the province of this application, clinical research on human cataractogenesis, hopefully, will be based on information deriving from this basic research program.