Structural Evidence of Human Nuclear Fiber Compaction as a Function of Ageing and Cataractogenesis

Al-Ghoul, K. J.; Nordgren, Rachel; Kuszak, Adam; Freel, Christopher D.; Costello, M. Joseph; Kuszak, J.R.

doi:10.1006/exer.2000.0937

Cited by 97 publications

(66 citation statements)

References 29 publications

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“…Also measurements of lens hardness [30,35] have shown that there are mechanical differences between the lens nucleus and the cortex. This is further supported by lens morphology [1,36], which shows a compaction of fibres toward the lens centre. Other differences have also been observed between the lens nucleus and cortex in terms of the protein gradient [13], refractive index [33] and acoustic parameters [26].…”

Section: Introductionmentioning

confidence: 58%

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Stiffness gradient in the crystalline lens

Weeber

Eckert

Pechhold

et al. 2007

Graefes Arch Clin Exp Ophthalmol

140

147

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Background While the overall stiffness of the lens has been measured in a number of studies, the knowledge about the stiffness distribution within the lens is still limited. The purpose of this study was to determine the stiffness gradient in the human crystalline lens. A secondary purpose was to determine whether the stiffness gradient depends on age. Methods The local dynamic stiffness was measured in 10 human crystalline lenses (age range: 19 to 78 years). The lenses were stored at −70°C before being measured. The influence of freezing on the mechanical properties has been determined in a previous study. A small oscillating probe was used to measure the local dynamic shear modulus as a measure of lens stiffness. The measurements were taken in the cross-sectional plane through the lens equator. Results The local dynamic shear modulus varied with location for all tested lenses. The central stiffness of the oldest lens (78 years) was 10 4 times higher than the youngest (19 years) lens. The equatorial stiffness of the oldest lens was 10 2 times higher than the youngest lens. For the older lenses, the centre was 5.8-210 times stiffer than the periphery, as opposed to earlier results described by Fisher (1971), who found that the periphery was up to 3 times softer than the centre for lenses younger than 70-years-old. For the three youngest lenses (19 to 49 years), the periphery was 2.2-16.6 times stiffer than the centre. Conclusions The dynamic stiffness of the crystalline lens varies with location within the lens. The stiffness gradient depends on the age of the lens. The results of the 10 lenses indicate that the stiffness of both centre and periphery increase with age, but at a different rate.

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Section: Introductionmentioning

confidence: 58%

“…Recently, Al-Ghoul et al [1] quantified the compaction of the lens fibres in the fetal and embryonic nucleus of adult lenses. The authors suggested that lens fibre compaction may cause an increase in lens hardness, which contributes to the loss of accommodation.…”

Section: Lens Changes and Stiffness Profilesmentioning

confidence: 99%

Stiffness gradient in the crystalline lens

Weeber

Eckert

Pechhold

et al. 2007

Graefes Arch Clin Exp Ophthalmol

140

147

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“…Such an increase in the density of lens fi ber cells with age in the barrier region may be one factor that contributes to the formation of the barrier by increasing the number of cellular membranes that need to be crossed by small molecules diffusing toward the lens center. Electron microscopic evidence also suggests that compaction may occur in some areas of the human lens with age ( 37 ).…”

Section: Changes In Sphingomyelin Content Of the Barrier Region With Agementioning

confidence: 98%

Sphingolipid distribution changes with age in the human lens

Deeley

Hankin

Friedrich

et al. 2010

Journal of Lipid Research

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characterizing these can have clinical relevance for understanding the molecular basis of ocular conditions such as presbyopia ( 2 ) and nuclear cataract ( 3, 4 ).It is not known which are the critical factors predisposing the human lens to age-related nuclear (ARN) cataract. Research from one of us, over many years, suggests that the formation of an internal barrier to the diffusion of small molecules may be a key event in the onset of this pathology ( 5, 6 ). The barrier forms in the normal lens at middle age and uncouples the center of the lens from the metabolically active outer region. Because the lens grows continuously throughout life, the outmost part of the lens is the region that was formed most recently and has the highest concentration of active enzymes ( 7,8 ). It is where the major antioxidant glutathione (GSH) is synthesized and the oxidized form of glutathione rereduced ( 9, 10 ). Since GSH is essential for maintaining a reducing environment in the lens center and for protection of protein structure, formation of the barrier allows oxidative modifi cation of nuclear proteins that is the hallmark of nuclear cataract. The dimensions of the barrier region (7 mm equatorial × 3 mm axial) corresponds to the part of the adult lens that was synthesized immediately after birth ( 11,12 ).Recent data implicate the binding of denatured proteins to the fi ber cell membrane as the mechanism responsible for the barrier ( 13 ), possibly by occluding the membrane pores that normally facilitate the movement of GSH and water from cell to cell via connexon ( 14 ) and aquaporin 0 ( 15 ) channels, respectively. Moreover, aquaporin 0 requires interaction with distinct membrane lipids to form its correct functional conformation ( 15 ). If interactions with fi ber cell Abstract The formation of an internal barrier to the diffusion of small molecules in the lens during middle age is hypothesized to be a key event in the development of age-related nuclear (ARN) cataract. Changes in membrane lipids with age may be responsible. In this study, we investigated the effect of age on the distribution of sphingomyelins, the most abundant lens phospholipids. Human lens Due to a lack of turnover ( 1 ), the lens is an ideal tissue for examining age-related changes to biomolecules, and

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“…Fourier transform infrared spectroscopy confirmed the majority of secondary structure in lens proteins to be in the form of β pleated sheet, which gives origin to the strong 1670 cm −1 infrared amide I band [40]. Scanning electron microscopy of human lenses belonging to various age groups was employed for better understanding of tertiary and quaternary structure of protein fibers and membrane layers as well [2]. Raman microscopic study, also done on human lenses, concentrated on distribution of tyrosine and tryptophane amino acids in different sections of the lens [41].…”

Section: Discussionmentioning

confidence: 99%

“…These fibres are encapsuled by a layer of epithaxial cells from the anterior side, perpendicularly to the optical axis of the lens, and contain a bunch of embrionic fibres at the lens center [2]. Thus in every lens the central part is the oldest one, and the youngest fibres are at the periphery (cortex).…”

Section: Introductionmentioning

confidence: 99%

Development of cataract caused by diabetes mellitus: Raman study

Furić

Mohaček-Grošev

Hadžija

2005

Journal of Molecular Structure

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Diabetes mellitus succeeded by diabetic cataract was induced to experimental animals (Wistar rats) by applying an Alloxan injection. Eye properties deterioration were monitored from clinical standpoint and using Raman and infrared spectroscopies. All cases of developed cataract were followed by important changes in vibrational spectra, but Raman spectroscopy proved to be more useful because of larger number of resolved bands. Each kth Raman spectrum of diseased lens (in our notation k denotes disease age and cataract degree as described in chapter Alloxan diabetes) can be expressed as a sum of the Raman spectrum of healthy lens, I R , multiplied by a suitable constant c k , and the fluorescent background spectrum, I FB . We introduce the ratio of integrated intensities I FB and c k *I R as a physical parameter called fluorescent background index F FB . It turns out that F FB grows as cataract progresses and has its maximum at approx. 4, whence it decreases. F FB values are larger for 200-1800 cm −1 spectral interval than for 2500-4000 cminterval.In the same manner another quantity called water band index F W is defined for each Raman spectrum of diseased lens in the 2800-3730 cm −1 interval. It is the ratio of the integrated intensity from 3100 to 3730 cm −1 (water band interval) divided by the integrated intensity of the 2800-3100 cm −1 interval (C-H stretching region). F W increases monotonously with cataract progression with maximum at the end of monitored period (5 months).These two indices helped us to formulate a model describing disease development from the earliest molecular changes to its macroscopic manifestation. As glucose and other small saccharide molecules enter the lens tissue, they bind to crystallin and other proteins via O -and Sglycosidic linkages which occur probably at tyrosine and cystein sites. In Raman spectrum this corresponds to broad bands at 540 and 1100 cm −1 which grow together with the fluorescent background, because both contributions originate in nonenzimatically glycated proteins. The maximum of possible binding ends after approximately 4 months (cataract degree 4), but the water continues to enter the tissue and resides in water agglomerates.The lens impairing caused by fluorescent light scattering on aberrant glycoproteins and other fluorescent centers appears first and is usually associated with the ageing cataract, while deterioration of lens properties caused by increased binding of water steadily rises with glucose Furić, K., Mohaček-Grošev, V., Hadžija, M. (2005), ''Development of cataract caused by diabetes mellitus: Raman study '' Journal of Molecular Structure, and is characteristic of diabetic cataract. This interpretation is in agreement with electron microscopy results of other groups and with our preliminary findings obtained with light microscopy.

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Structural Evidence of Human Nuclear Fiber Compaction as a Function of Ageing and Cataractogenesis

Cited by 97 publications

References 29 publications

Stiffness gradient in the crystalline lens

Stiffness gradient in the crystalline lens

Sphingolipid distribution changes with age in the human lens

Development of cataract caused by diabetes mellitus: Raman study

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