Anisotropic Water Transport in the Human Eye Lens Studied by Diffusion Tensor NMR Micro-imaging

doi:10.1006/exer.2001.1164

Experimental Eye Research

Volume 74, Issue 6, June 2002, Pages 677-687

https://doi.org/10.1006/exer.2001.1164 Get rights and content

Abstract

We report in vitro measurements of effective diffusion tensors characterising the anisotropic transport of water in human eye lenses ranging in age from 13 to 86 years. The measurements were obtained by means of a pulsed field gradient spin echo (PFGSE) magnetic resonance imaging (MRI) technique at a spatial resolution of 218 × 218 × 1000 μm³. The results show that water diffusion is both spatially inhomogeneous and highly anisotropic on the timescale of the measurements (approximately 15 msec). Diffusion parallel to the long axes of the lens fibre cells is relatively unrestricted, whereas that between cells is substantially inhibited by the cell membranes, particularly in the inner cortex region of the lens. The data confirm the presence of a diffusion barrier surrounding the lens nucleus, which inhibits transport of water and other small molecules into and out of the nucleus. The results shed light on factors that may influence the onset of presbyopia and senile cataract. They also have implications for delivery of drugs to the lens nucleus.

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Structural proteins: Crystallins of the mammalian eye lens
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Some of the oldest vertebrate proteins reside in the eye lens, and these include the crystallins. Lifelong protein preservation, as opposed to protein turnover, maintains lens transparency through the molecular chaperone action of the mammalian α-, β-, and γ-crystallins. The lenticular chaperone α-crystallin consists of αΑ- and αΒ-crystallin, while the βγ-crystallins also develop the gradient refractive index of the lens. Mutations and accumulated post-translational modifications in the crystallins cause cataract; the interplay between physiological crystallin function, protein crowding, phase separation, and the accumulation of cataractogenic load are essential to forwarding our understanding of the aging process.
Dielectric properties of healthy and diabetic alloxan-induced lenses in rabbits
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The dielectric properties of the eye lens were studied for healthy and alloxane-induced diabetic rabbits in the frequency range from 500 Hz to 100 kHz electric field and temperatures from 25 to 50 °C. In the full temperature range, the average relative permittivity and dielectric loss values for a healthy lens are lower than those recorded for diabetic tissue. Dielectric relaxation of polar amino acids on the alpha-crystallin surface with a characteristic frequency of 7 kHz in the range of 25–50 °C for healthy and diabetic samples is accompanied by the activation energy of proton conductivity with an average values of 33 and 39 kJ mol⁻¹, respectively. The permittivity decrement, which characterizes the size of the dielectric dispersion with a central relaxation time of 0.023 ms for a diabetic sample, is more than twice as high as for a healthy sample. Measurements on the rabbit eye lens were carried out at ambient temperature above and below the physiological range, since these conditions provide an appropriate pattern of dielectric behavior for the diagnosis of clinical dysfunction of the human lens.
Multi-parametric MRI of the physiology and optics of the in-vivo mouse lens
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Citation Excerpt :
Finally, MRI can be used to measure lens geometry (the surface curvatures, conic constants, and thicknesses) non-invasively, without concerns of optical distortions. The utility of these MRI modalities has been demonstrated in several studies: T1 and T2 mapping of organ-cultured bovine and rat lens under pharmacological perturbations or treatments [4,9,10], DTI to study water diffusion patterns within the lens [11,12], and calibration of T2 with the lens GRIN in human ex vivo lenses [12,13]. However, the majority of these studies were limited to ex-vivo lenses, with in vivo studies of the lens being limited to a few studies in large animals [14] and humans [15,16], which can suffer from issues associated with motion artefacts, magnetic susceptibility artefacts in the anterior eye, and the high protein content of the lens.
The optics of the ocular lens are determined by its geometry (shape and volume) and its inherent gradient of refractive index (water to protein ratio), which are in turn maintained by unique cellular physiology known as the lens internal microcirculation system. Previously, magnetic resonance imaging (MRI) has been used on ex vivo organ cultured bovine lenses to show that pharmacological perturbations to this microcirculation system disrupt ionic and fluid homeostasis and overall lens optics. In this study, we have optimised in vivo MRI protocols for use on wild-type and transgenic mouse models so that the effects of genetically perturbing the lens microcirculation system on lens properties can be studied. In vivo MRI protocols and post-analysis methods for studying the mouse lens were optimised and used to measure the lens geometry, diffusion, T1 and T2, as well as the refractive index (n) calculated from T2, in wild-type mice and the genetically modified Cx50KI46 mouse. In this animal line, gap junctional coupling in the lens is increased by knocking in the gap junction protein Cx46 into the Cx50 locus. Relative to wild-type mice, Cx50KI46 mice showed significantly reduced lens size and radius of curvature, increased T1 and T2 values, and decreased n in the lens nucleus, which was consistent with the developmental and functional changes characterised previously in this lens model. These proof of principle experiments show that in vivo MRI can be applied to transgenic mouse models to gain mechanistic insights into the relationship between lens physiology and optics, and in the future suggest that longitudinal studies can be performed to determine how this relationship is altered by age in mouse models of cataract.
The physiological optics of the lens
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The optical properties of the ocular lens are important to overall vision quality. As a transparent biological tissue, the lens contributes to the overall and dynamic focussing power of the eye, and corrects for optical errors introduced by the cornea. The optical properties of the lens change throughout life. Alterations to the refractive properties and transparency of the lens result in presbyopia and cataract, respectively. However, it is not well understood how changes to lens cellular structure and function initiate these changes in refraction and transparency. Here, we attempt to bridge this knowledge gap by reviewing how the optical properties of the lens are first established, and then maintained at the cellular level throughout the lifetime of an individual. Central to this understanding is the fact that the lens has a microcirculation system that generates a flux of ions and water that circulates through the lens. By supporting ionic and metabolic homeostasis in the lens, the system actively maintains lens transparency, and by regulating the steady state water content of the lens, controls the two key parameters, lens geometry and the gradient of refractive index, which determine the refractive properties of the lens. Thus, water transport is emerging as the critical parameter that links the transparency and refractive properties of the lens at the cellular level, and highlights the need to study how age-related changes in water transport result in presbyopia and cataract, the leading causes of refractive error and blindness in the world today.
Spatial distribution of metabolites in the human lens
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Spatial distribution of 34 metabolites along the optical and equatorial axes of the human lens has been determined. For the majority of metabolites, the homogeneous distribution has been observed. That suggests that the rate of the metabolite transformation in the lens is low due to the general metabolic passivity of the lens fiber cells. However, the redox processes are active in the lens; as a result, some metabolites, including antioxidants, demonstrate the “nucleus-depleted” type of distribution, whereas secondary UV filters show the “nucleus-enriched” type. The metabolite concentrations at the lens poles and equator are similar for all metabolites under study. The concentric pattern of the “nucleus-depleted” and “nucleus-enriched” distributions testifies that the metabolite distribution inside the lens is mostly governed by a passive diffusion, relatively free along the fiber cells and retarded in the radial direction across the cells. No significant difference in the metabolite distribution between the normal and cataractous human lenses was found.
Magnetic resonance imaging (MRI) study of the water content and transport in rat lenses
2013, Experimental Eye Research
Citation Excerpt :
Thus, T2-mapping of the lens allows for the quantitative measurements of the refractive index distribution (Jones and Pope, 2004; Jones et al., 2005, 2007; Kasthurirangan et al., 2008). Diffusivity mapping demonstrated that water movement inside the lens is highly anisotropic (Moffat and Pope, 2002a; Vaghefi et al., 2009): diffusion along the fiber cells is relatively free, while the movement between cells is restricted by the cell membranes. The diffusion in the lens nucleus is significantly slower than in the cortex (Moffat et al., 1999; Vaghefi et al., 2009); with aging, the diffusion rate in the cortex changes insignificantly, whereas in the nuclei of 80-year-old human lenses it is 3–4 times slower than in young lenses.
NMR micro-imaging technique has been used for the measurement of the water content distribution in lenses of senescence-accelerated OXYS rats and age-matched Wistar rats, as well as for the study of water and phosphate transport in rat lenses. The water content in the lens cortex is significantly higher than in the nucleus; the spatial gradient of the water content becomes steeper with age. No difference in the water content distribution has been found between Wistar and OXYS rat lenses of matching ages, although cataract onset in the OXYS rat lens occurs much earlier due to the enhanced generation of reactive oxygen species associated with oxidative stress. This finding implies that cataract development does not lead to significant changes in water content distribution inside the lens. The water transport in rat lenses slows down with age, and in OXYS lenses it is somewhat faster than in lenses of Wistar rats, probably due to the compensatory response to oxidative stress. The application of ³¹P MRI for the monitoring of phosphate penetration into a lens has been performed for the first time. It is found that phosphate transport in a lens is significantly slower than that of water.

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^f1: Author for correspondence. E-mail: [email protected]

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Regular ArticleAnisotropic Water Transport in the Human Eye Lens Studied by Diffusion Tensor NMR Micro-imaging

Abstract

Exp. Eye Res.

Exp. Eye Res.

Magn. Reson. Imaging

Semin. Cell Biol.

Exp. Eye Res.

Surv. Ophthalmol.

Magn. Reson. Imaging

Exp. Eye Res.

Magn. Reson. Imaging

Exp. Eye Res.

Biochim. Biophys. Acta

Exp. Eye Res.

Diffusion properties of water in the human crystalline lens during cataract development

Biofizika

Do changes in the hydration of the diabetic human lens precede cataract formation?

Res. Commun. Mol. Pathol. Pharmacol.

Regular Article
Anisotropic Water Transport in the Human Eye Lens Studied by Diffusion Tensor NMR Micro-imaging