The lens cells and their protein constituents have to remain functional for a lifetime to preserve the transparent function of the lens. Damage to lens proteins results in protein aggregation and cataract. Efficient removal and/or repair of damaged lens proteins is essential to prevent protein aggregation and cataract formation. The damage is normally prevented and repaired through the action of multiple anti-oxidant, chaperone and protein repair enzymes. Damaged proteins that are not repairable must be degraded to prevent aggregation and precipitation, a major mechanism of cataractogenesis. Our previous work demonstrated that a proteolytic system named the ubiquitinproteasome pathway plays an important role in selective removal of damaged or abnormal proteins from lens cells. To directly test the role of the ubiquitin-proteasome pathway in quality control of lens proteins, we will test whether impairment of the ubiquitin-proteasome pathway increases levels of various forms of damaged proteins in the lens and reduces lens transparency. The proposed work will increase our knowledge of how the lens maintains its transparent function and will potentially identify targets of pharmaceutical interventions for prevention or treatment of age-related cataract.
Cataract is the most common age-related eye diseases. Currently surgery is only effective methods to restore the vision loss caused by cataract. Elucidating the molecular mechanisms of cataract formation will help to develop safer, cheaper and more effective methods to prevent or treat agerelated cataract. During the last grant period we demonstrate that the ubiquitin-proteasome pathway is an important protein quality control mechanism in the lens. The selective degradation of various forms of damaged proteins by this pathway is important for preventing the accumulation and precipitation of damaged proteins in the lens. This proposed project will continue our work to demonstrate the critical role of the ubiquitin-proteasome pathway in maintaining lens transparency. Results from this project will help us to design new strategies for prevention and treatment of cataract.
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