The opacification of eye lens, cataract, is the leading cause of blindness worldwide. Several risk factors have been identified in the pathogenesis of cataract including UV exposures, genetics or induced by other diseases such as diabetes. Clinically, available medications to slow down cataract formation or to reverse cataracts are limited. Therefore, drug development for anti-cataractogenesis is attention. Our laboratory recently reported two compounds possessing anti-cataract properties with different chemical mechanisms. Astaxanthin with an electron-rich 冗-conjugated moiety interacts coordinately with electron-poor selenium of selenite anion. Binding of the selenite anion with aromatic ring systems of the pirenoxine anion suggest another interacted model. Curcumin itself has been demonstrated its ability to ameliorate selenite-induced lens turbidity. Biochemical mechanisms underlying curcumin’s anti-cataract activities are still unclear. Our laboratory established a series in vitro anti-cataract screening systems by excess selenite, calcium, or UV irradiations to induce lens turbidity formations. This proposal aims to apply theoretical chemistry, biophysical techniques (UV/Vis titration studies, FT-IR, 1H-NMR, 13C-NMR, 77Se-NMR, ITC, molecular orbital calculation) to determine whether curcumin interacts with selenite or calcium while compared to its analogues. In addition to test protective effects of lead compounds against UV irradiation, the compounds which possessing inhibitory effects on lens epithelial cells proliferations will be considered to be able to prevent cataract re-formation after cataract surgery. The specific epithelial biomarkers modulated by anti-cataract compounds will be identified by proteome. Differences between curcumin and curcumin derivatives will be discussed. In summary, this proposal is to apply cataract induced by various pathological factors to compare biochemical mechanisms of curcumin and each derivative. The lead compound for each pathological condition may be developed for specific needs in lens protections.
|Effective start/end date||8/1/15 → 7/31/16|
- curcumin derivatives
- selenite-binding moiety
- lens epithelial cell proliferation