The molecular processes involved in age-related human nuclear cataract

Funding Activity

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Funded Activity Summary

This project seeks to understand the molecular basis for age-related nuclear cataract, and in particular the role of our UV filter compounds. By gaining an understanding of the mechanism of cataract we hope to be able to develop ways to interfere with the process and thus prevent, or at least delay, human cataract. Experiments will be undertaken to determine the extent of covalent binding of the most reactive UV filter, 3-hydroxykynurenine, to lens proteins (crystallins) isolated from normal human lenses of various ages, and from cataract lenses. In addition, the properties of lens crystallins that have been modified in model systems by kynurenine, 3-hydroxykynurenine and 3-hydroxykynurenine glucoside will be investigated. This will include examination of the impact of the UV filter modifications on the formation of protein radicals following exposure of the crystallins to UV light and an investigation of the hypothesis that the protein-bound UV filters act as sites for both complexing of metals and their chemical reduction. Oxidation is known to be involved in cataract and experiments will also be undertaken to measure the concentration of oxygen in the lens nucleus, so that the model studies more accurately reflect conditions within the lens, and to see if the levels of oxygen may inflluence the onset of cataract.

Funded Activity Details

Start Date: 01-01-2004

End Date: 01-01-2006

Funding Scheme: NHMRC Project Grants

Funding Amount: $450,750.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Medical Biochemistry: Proteins and Peptides (incl. Medical Proteomics)

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Blindness | Cataract | Mechanism of Lens aging - physiology and biochemistry | Post translational modification of proteins | Protein oxidation | UV light | Vision