December 2002
Volume 43, Issue 13
ARVO Annual Meeting Abstract  |   December 2002
Protein Modification by the Trp metabolite, Kynurenine, in Human Lenses
Author Affiliations & Notes
  • RJ Truscott
    Dept of Chemistry Australian Cataract Res Foundation Wollongong Australia
  • S Vazquez
    Wollongong Australia
  • LM Taylor
    Wollongong Australia
  • MM Sheil
    Dept of Chemistry
    Wollongong Australia
  • Footnotes
    Commercial Relationships   R.J. Truscott, None; S. Vazquez , None; L.M. Taylor , None; M.M. Sheil , None. Grant Identification: NHMRC
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 2388. doi:
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      RJ Truscott, S Vazquez, LM Taylor, MM Sheil; Protein Modification by the Trp metabolite, Kynurenine, in Human Lenses . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2388.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract: : Purpose: As the human lens ages, it undergoes a number of biochemical changes that affect our vision. For example, the older the person, the more yellow is their lens, and therefore the amount of blue light transmitted to the retina is correspondingly diminished. We aim to understand these changes that may result ultimately in the development of age-related cataract. Methods: Intact human lenses, and model systems employing calf lens proteins in the presence of UV filters, have been studied. We have shown that the onset of a barrier within the lens at middle age, leads to a number of alterations in lens metabolism and predisposes the lens to subsequent nuclear cataract. One consequence of the barrier, is an increased residence time, within the lens interior, of the UV filters that are present. In man, these are tryptophan metabolites including kynurenine, 3-hydroxykynurenine and 3-hydroxykynurenine glucoside. These derivatives are intrinsically unstable at pH 7 and deaminate to produce reactive unsaturated ketones. Results: We show here that UV filter breakdown results in the progressive accumulation of kynurenine bound covalently to the structural proteins in the human lens. This novel post-translational modification, involves His, Lys and Cys residues, and occurs to the greatest extent in the nuclear proteins of older lenses. Glutathione is the key antioxidant in the lens that can act to intercept these reactive intermediates before they bind to the structural proteins. By contrast, ascorbate is completely ineffective. Conclusion: Modification of human lens proteins by UV filters occurs after middle age, and plays a major role in normal lens coloration. It is likely that such post-translational changes predispose older lenses to nuclear cataract.

Keywords: 338 cataract • 309 aging 

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