Abstract
Abstract: :
Purpose: A UV filter pathway is present in primates to protect the lens and retina from UV damage. This is located in the lens and is based on the production of kynurenine metabolites. Unfortunately such compounds are unstable, and in lenses after middle age, they react with structural proteins causing lenses to become colored. We are investigating whether this loading of proteins with UV filters may also play a major part in the development of cataract. Methods: The levels of protein–bound kynurenine in normal lenses and in Age–Related Nuclear (ARN) cataract lenses were quantified by HPLC after acid hydrolysis of the proteins Results: After middle age, the concentration of protein–bound UV filters in lenses increases. In model studies where crystallins were incubated with kynurenine (Kyn), cysteine residues were the preferred target, however in older human lenses the levels of His–Kyn and Lys–Kyn were greater than those of Cys–Kyn. The explanation for this appears to be based on the relative stabilities of the different Kyn–amino acid adducts. Cys–Kyn decomposes readily. Thus the final pattern of modification in the lens seems to be a reflection more of adduct stability, than the rate of formation. The levels of His–Kyn and Lys–Kyn in nuclear proteins from ARN cataract lenses were found to decrease with the progression of the cataract. Exposure to O2 or hydrogen peroxide was not responsible for this reduction. This may indicate that other reactions take place in these lenses after the initial binding of the UV filters. Conclusion: The modification of proteins by UV filters in the human lens is a dynamic process where the final pattern of modification observed seems to reflect the stabilities of the adducts, rather than the initial covalent attachment. Decomposition of the protein–bound UV filters in cataract lenses could possibly be responsible for the characteristic coloration of these lenses.
Keywords: cataract • aging • antioxidants