Quasielastic light scattering study of the living human lens as a function of age

Thurston, George M.; Hayden, Douglas; Burrows, Pendra; Clark, John I.; Taret, Victor G.; Kandel, Joel; Courogen, Maria; Peetermans, Joyce; Bowen, M. Shane; Miller, David; Sullivan, Keith M.; Storb, Rainer; Stern, Hal; Benedek, George B.

doi:10.1076/ceyr.16.3.197.15410

Cited by 43 publications

(26 citation statements)

References 17 publications

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“…A systematic approach examining several regions within each lens in a number of lenses in the future will permit the creation of a library of fiber cells from different clinical cataract grades and corresponding scattering. Comparison of these with in vivo methods of estimating the optical properties of the aging lens using light scattering as a tool, some of which have been demonstrated before (Thurston et al, 1997), will allow estimates of the contribution of cytoplasmic packing to overall opacity. In particular, this may lead to the refinement of objective clinical cataract grading, taking into account objective measures of both back scattering and forward scattering in the in vivo lens.…”

Section: Discussionmentioning

confidence: 99%

Analysis of nuclear fiber cell cytoplasmic texture in advanced cataractous lenses from Indian subjects using Debye–Bueche theory

Metlapally

Costello

Gilliland

et al. 2008

Experimental Eye Research

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Alterations in ultrastructural features of the lens fiber cells lead to scattering and opacity typical of cataracts. The organelle-free cytoplasm of the lens nuclear fiber cell is one such component that contains vital information about the packing and organization of crystallins critical to lens transparency. The current work has extended analysis of the cytoplasmic texture to transparent and advanced cataractous lenses from India and related the extent of texturing to the nuclear scattering observed using the Debye-Bueche theory for inhomogeneous materials. Advanced age-related nuclear cataracts (age-range 38-75 years) and transparent lenses (age-range 48-78 years) were obtained following extracapsular cataract removal or from the eye bank, at the L. V. Prasad Eye Institute. Lens nuclei were Vibratome-sectioned, fixed and prepared for transmission electron microscopy using established techniques. Electron micrographs of the unstained thin sections of the cytoplasm were acquired at 6500X and percent scattering for wavelengths 400-700 nm was calculated using the Debye-Bueche theory. Electron micrographs from comparable areas in an oxidative-damage sensitive (OXYS) rat model and normal rat lenses preserved from an earlier study were used, as they have extremely textured and smooth cytoplasms, respectively. The Debye-Bueche theoretical approach produces plots that vary smoothly with wavelength and are sensitive to spatial fluctuations in density. The central lens fiber cells from advanced cataractous lenses from India and the OXYS rat, representing opaque lens nuclei, produced the greatest texture and scattering. The transparent human lenses from India had a smoother texture and less predicted scattering, similar to early cataracts from previous studies. The normal rat lens had a homogeneous cytoplasm and little scattering. The data indicate that this method allowed easy comparison of small variations in cytoplasmic texture and robustly detected differences between transparent and advanced cataractous human lenses. This may relate directly to the proportion of opacification contributed by the packing of crystallins. The percent scattering calculated using this method may thus be used to generate a range of curves with which to compare and quantify the relative contribution of the packing of crystallins to the loss of transparency and scattering observed.

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Section: Discussionmentioning

confidence: 99%

Analysis of nuclear fiber cell cytoplasmic texture in advanced cataractous lenses from Indian subjects using Debye–Bueche theory

Metlapally

Costello

Gilliland

et al. 2008

Experimental Eye Research

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“…The presence of such aggregates was quickly confirmed by studies by Spector et al [99]and Jedziniak et al [100], and attributed to the presence of disulphide cross-linking [101]. Since studies by Yu et al [102]have failed to show the presence of such cross-links in clear human lenses up to and greater than 65 years in age, it would appear that the exponential increase in back scattering observed in cataract-free lenses (for instance by quasi-elastic light scattering) [103]is due, for instance in the nucleus of the lens, to the presence of complexes, referred to earlier, formed between α-crystallin and unfolded β- and, to a lesser extent, γ-crystallins. Unfolding is caused by post-translational modifications brought about by glycation, carbamylation, methionine oxidation and racemisation.…”

Section: Scatter Absorption and Fluorescencementioning

confidence: 99%

The Ageing Lens

et al. 2000

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The human lens grows by a process of epithelial cell division at its equator and the formation of generations of differentiated fibre cells. Despite the process of continuous remodelling necessary to achieve growth within a closed system, the lens can retain a high level of light transmission throughout the lifetime of the individual, with the ability to form sharp images on the retina. Continuous growth of the lens solves the problem imposed by terminal differentiation within a closed, avascular system, from which cells cannot be shed. The lens fibre tips arch over the equator to meet anteriorly and posteriorly and form branching sutures of increasing complexity. The stages of branching may create the optical zones of discontinuity seen on biomicroscopy. The lens is exposed to the cumulative effects of radiation, oxidation and postranslational modification. These later proteins and other lens molecules in such a way as to impair membrane functions and perturb protein (particularly crystallin) organisation, so that light transmission and image formation may be compromised. Damage is minimised by the presence of powerful scavenger and chaperone molecules. Progressive insolublisation of the crystallins of the lens nucleus in the first five decades of life, and the formation of higher molecular weight aggregates, may account for the decreased deformability of the lens nucleus which characterises presbyopia. Additional factors include: the progressive increase in lens mass with age, changes in the point of insertion of the lens zonules, and a shortening of the radius of curvature of the anterior surface of the lens. Also with age, there is a fall in light transmission by the lens, associated with increased light scatter, increased spectral absorption, particularly at the blue end of the spectrum, and increased lens fluorescence. A major factor responsible for the increased yellowing of the lens is the accumulation of a novel fluorogen, glutathione-3-hydroxy kynurenine glycoside, which makes a major contribution to the increasing fluorescence of the lens nucleus which occurs with age. Since this compound may also cross-link with the lens crystallins, it may contribute to the formation of high-molecular-weight aggregates and the increases in light scattering which occur with age. Focal changes of microscopic size are observed in apparently transparent, aged lenses and may be regarded as precursors of cortical cataract formation.

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“…It has been shown that the backscattering of light from these aggregates increases exponentially with age. 13 The lens fibers are unusual in that for mature lenses, the nucleus, endoplasmic reticulum and mitochondria are absent, contributing to the overall transparency of the lens. The lens fibers also have an extensive cytoskeleton helping to maintain consistent packing of the cell structure.…”

Section: Introductionmentioning

confidence: 99%

Cavitation rheology of the eye lens

et al. 2011

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The anisotropic mechanical properties of bovine eye lenses were measured using cavitation rheology over a range of length scales. The technique involves inducing a cavity at the tip of a syringe needle in different regions of the lens. Effective Young's moduli of the nucleus and cortex of the lens were determined, as approximately 11.8 and 0.8 kPa, respectively, on macroscopic length scales. We also measured the mechanical properties of the lens on the length scale of a single cell, suggesting that the stiffness significantly decreased from that in the bulk measurements for both the nucleus and cortex. In addition, during the growth of the cavity anisotropic propagation in the cortex was observed, while in the nucleus, the propagation was isotropic. We further explored the elasticity of the cavity deformation, showing both elastic and inelastic deformation occurred in the nucleus with equal contributions while deformation in the cortex was elastic and reversible.

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Quasielastic light scattering study of the living human lens as a function of age

Abstract: This methodology permits a sensitive, quantitative, clinically useful representation of the pre-cataractous molecular changes associated with aging in the living human lens.

Cited by 43 publications

References 17 publications

Analysis of nuclear fiber cell cytoplasmic texture in advanced cataractous lenses from Indian subjects using Debye–Bueche theory

Analysis of nuclear fiber cell cytoplasmic texture in advanced cataractous lenses from Indian subjects using Debye–Bueche theory

The Ageing Lens

Cavitation rheology of the eye lens

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