Purchase this article with an account.
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.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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.
This PDF is available to Subscribers Only