A BRIEF PHOTOCHEMICALLY INDUCED OXIDATIVE INSULT CAUSES IRREVERSIBLE LENS DAMAGE AND CATARACT .2. MECHANISM OF ACTION

Using photochemically induced oxidative stress and rat lenses in organ culture with 4% O-2 and 4 mu M riboflavin, it has been found that the observed changes in lens parameters are, in most cases, irreversible. This has made possible the elucidation of the sequence of biological changes leading to cataract. The earliest detectable changes in lens c ell biology are observed in the epithelial cell redox set point and at the DNA level in terms of DNA integrity and H-3-thymidine incorporati on followed by decreased membrane transport and changes in gene expres sion. Significant modification in classical cataract parameters such a s hydration, steady state non-protein thiol, glyceraldehyde-phosphate- dehydrogenase activity and transparency occur at later times. The data suggest a definitive pattern of lens breakdown resulting in opacity s tarting at the epithelial cell level and leading to subsequent fibre c ell involvement.