Mobility of Chromophores Absorbing Light in the 320–420 nm Range in Transparent and Cataract Lens Tissue

Abstract

We have analyzed the spectral and kinetic characteristics of phosphorescence at room temperature on a millisecond time scale for transparent and cataract lens tissues. We have studied the nature of the change (with age and with cataract development in the lens tissues) in the molecular mobility of the products absorbing light in the 320-420 nm range.Keywords: bovine and human transparent lenses, human cataract lenses, phosphorescence at room temperature, age-related cataract.Introduction. Human lens tissue is characterized by a high level of posttranslational modifi cations of proteins accumulating with age, due to the very high content of protein macromolecules in them compared with other tissues in the body [1]. The main targets for modifi cation are crystallins, comprising ≈90% of all lens proteins [2]. A healthy lens contains low molecular weight substances absorbing UV radiation in the 300-400 nm range. These substances ("UV fi lters") are metabolites of tryptophan: kynurenine (KN) and its derivatives 3The main reason for age-related posttranslational modifi cations of lens proteins is fragmentation of the kynurenine-containing UV fi lters (3OHKG, KN, and 3OHKN) followed by their subsequent addition via covalent bonds to proteins [3] and reduced glutathione (GSH) [4] with formation of protein-bound kynurenines and the compounds GSH-KN, GSH-3OHKN, and GSH-3OHKG. Since these substances are more photochemically active than the original UV fi lters, they are responsible for the formation of active oxygen species promoting development of cataract with age [5]. The decrease of free, not protein-bound UV fi lters (KN, 3OHKG, 3OHKN) with age in lens tissue is ≈12% per decade [6].One more lens protein posttranslational modifi cation process is glycation. αB-Crystallin is the predominant protein in lenses and belongs to the family of small heat shock proteins, which is a large class of molecular chaperones that interact with partially denatured proteins to prevent their aggregation. It is generally thought that the function of chaperones is not vital for maintaining lens transparency and preventing cataract development. In model experiments, it was shown [7] that formation of advanced glycation end products (AGEs) leads to a decrease in chaperone activity of αB-crystallin relative to the proteins alcohol dehydrogenase, insulin, and citrate synthase selected as substrates.In lenses of the elderly, with cataract development we observe an increase in non-disulfi de protein crosslinks. Some researchers have identifi ed yellow chromophores bound to lens proteins. Hypothetically, many of these components are AGEs, which absorb light in the UV-A region (320-400 nm). Since 1000 times more light in the UV-A range is incident on the lens than in the UV-B range (280-320 nm), the presence of AGEs can enhance photo-induced damage to lens proteins. When the proteins are highly modifi ed, they become part of the water-insoluble fraction. This fraction consists of large protein aggregates that do not dissolve during homogenization. I...