Roger JW Truscott, Michael Friedrich,Michelle Hooi, Brian Lyons

Purpose:
To elucidate the molecular basis for humanage-related cataract.

Method:
Proteomic analysis of whole nuclei, dis-sected from lenses of cataract patients and age-matched normal controls, were utilised. Trypticdigestion was coupled with Liquid Chromatography/Mass Spectrometry/ Mass Spectrometry.

Results:
Over time, the crystallin proteins of the lens,which do not turn over, progressively degrade. Usingproteomic techniques we have been able to elucidatethe major modifications that take place with age.The main processes were found to be racemisation,deamidation and truncation.In many cases, the extent of modification at particularsites did not differ between the normal and the cataractlenses, however at certain sites there was a signifi-cantly greater degree of modification in the cataract lenses.

Conclusion:
Proteomics may have established theroot cause of the major human blinding condition,age-related cataract. Cataract appears to result fromsite-specific decomposition of particular long-livedmacromolecules in the human lens.