Our objective is to define the process of chemical protection from radiation-induced cataracts to further clarify the mechanisms of radiation cataract formation and the mechanisms of chemical radioprotection. Our ultimate goal is to develop a radioprotective drug with clinical utility. The formation of radiation cataracts involves both biochemical and histological changes in the lens of the affected eye which we will follow over time after radiation exposure. The addition of a drug substance which prevents the formation of cataracts should give valuable information on which parameters of lens biochemistry are important in the process of cataract formation, as we will be able to differentiate those factors whose alterations are coincident with eventual cataract formation. Conversely, biochemical alterations in irradiated lenses will give an early indication of lens pathology, allowing definition of those radiobiological factors which are necessary to develop a drug which protects against radiation cataracts. In preliminary studies, we have validated the concept of chemical protection by the radioprotective drug S-3-amino-2-hydroxypropyl-phorsphorothioic acid (WR-77913) against radiation cataracts. We propose studies of several parameters of lens biochemistry (phase transition temperature, protein precipitation, protein molecular weight distribution, and thiol redox status) which are known to be altered during cataract development. These studies will be performed on groups of animals which receive varying doses of either radioprotective drug or radiation. Dose-response relationships will be defined for these parameters which are important in lens radioprotection. Additionally, we will test the protective effect of WR-77913 against radiations of different quality (gamma rays and neutrons) and the effects of different radioprotective drugs (cysteamine, WR-2721 and their derivatives) on the biochemistry of radiation cataractogenesis.
