Age-related compaction of lens fibers affects the structure and optical properties of rabbit lenses

Al‐Khudari, Samer; Donohue, Sean T.; Al-Ghoul, Walid M.; Al-Ghoul, K. J.

doi:10.1186/1471-2415-7-19

“…PTMs, such as glycation, phosphorylation, deamidation, and oxidation, can lead to aggregation and cross-linking (8 -11, 34), but at the cellular level, these could be implicated in changes of lens fiber cell folds and breaks (35), extracellular spaces (36), suture subbranches (33), and fiber cell compaction (37,38). These cellular changes could be potential sources for light scattering, leading to age-related cataract development.…”

Section: Discussionmentioning

confidence: 99%

The Common Modification in αA-Crystallin in the Lens, N101D, Is Associated with Increased Opacity in a Mouse Model

Gupta

¹

,

Asomugha

²

,

Srivastava

³

2011

Journal of Biological Chemistry

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To elucidate the morphological and cellular changes due to introduction of a charge during development and the possible mechanism that underlies cataract development in humans as a consequence of an additional charge, we generated a transgenic mouse model mimicking deamidation of Asn at position 101. The mouse model expresses a human ␣A-crystallin gene in which Asn-101 was replaced with Asp, which is referred to as ␣AN101D-transgene and is considered to be "deamidated" in this study. Mice expressing ␣AN101D-transgene are referred to here CRYAA N101D mice. All of the lines showed the expression of ␣AN101D-transgene. Compared with the lenses of mice expressing wild-type (WT) ␣A-transgene (referred to as CRYAA WT mice), the lenses of CRYAA N101D mice showed (a) altered ␣A-crystallin membrane protein (aquaporin-0 (AQP0), a specific lens membrane protein) interaction, (b) extracellular spaces between outer cortical fiber cells, (c) attenuated denucleation during confocal microscopic examination, (d) disrupted normal fiber cell organization and structure during scanning electron microscopic examination, (e) distorted posterior suture lines by bright field microscopy, and (f) development of a mild anterior lens opacity in the superior cortical region during the optical coherence tomography scan analysis. Relative to lenses with WT ␣A-crystallin, the lenses containing the deamidated ␣A-crystallin also showed an aggregation of ␣A-crystallin and a higher level of water-insoluble proteins, suggesting that the morphological and cellular changes in these lenses are due to the N101D mutation. This study provides evidence for the first time that expression of deamidated ␣A-crystallin caused disruption of fiber cell structural integrity, protein aggregation, insolubilization, and mild cortical lens opacity.The ocular lens has a unique cellular architecture consisting of a single layer of cuboidal epithelial cells, which divide and differentiate at the equator into fiber cells (1). The fiber cells elongate, and they synthesize fiber cell-specific proteins, such as AQP0 (aquaporin-0)/MIP (main intrinsic protein), cytoskeletal proteins, and crystallins (1-4). As the new fiber cells are laid down at the lens equator, the older fiber cells are pushed toward the lens core and simultaneously lose their nuclei and organelles while exhibiting very little protein turnover. Among the three classes of the vertebrate lens crystallins (␣-, ␤-, and ␥-crystallins), ␣-crystallins are composed of two primary gene products, A and B, known as ␣A-and ␣B-crystallins, that show ϳ60% amino acid homology and constitute up to 50% of the total lens proteins. Both ␣A-and ␣B-crystallins belong to a family of small heat shock proteins with "chaperone" activity (5, 6). These crystallins are constitutively expressed in both lens epithelial and fiber cells (7) and undergo numerous age-related post-translational modifications (PTMs) 2 that lead to their unfolding, aggregation, and insolubilization. These PTMs eventually lead to accumulation of damaged crystal...

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“…It is noteworthy that these interruptions in the trend of gradual increase are roughly simultaneous with early and age-related degenerative alterations that affect intervertebral disks 24 , lens 25 , and fertility-associated trace elements 26 of rabbits. But more importantly, the same study that described continuous changes in testicular structure of rabbits until an age of two years, also showed that, at this time point, hypospermatogenesis is already noticeable 28 .…”

Section: Discussionmentioning

confidence: 99%

“…For example, in rabbits aged 30 or less months, agerelated degenerative changes have been detected in intervertebral disks 24 , lens 25 , and in the serum levels of fertility-associated trace elements 26 . Notably, changes in sexual behavior, as denoted by increased sexual exhaustion and impaired ejaculation 27 , as well as hypospermatogenesis 28 , have been shown to take place at around 20 months of age.…”

Section: Introductionmentioning

confidence: 99%

Age-related changes in the concentration of elastic fibers in different regions of the rabbit penis

Figueiredo

¹

,

Costa

²

,

Chagas³

et al. 2013

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PURPOSE:To investigate whether elastic fiber content in the corpus cavernosum (CC), corpus spongiosum (CS) and tunica albuginea (TA) of the rabbit penis undergoes modifications with age. METHODS:Rabbits were sacrificed, in groups of ten animals each, at 30, 120, 240, and 730 days of age. Histological sections were obtained from the penile middle shaft and were stained with Weigert's resorsin fuchsin. The content of elastic fibers was determined using stereological methods, and was expressed as volume fraction. RESULTS:At 730 days of age, elastic fiber content was increased by 54% (p<0.004), 78% (p<0.004), and 87% (p<0.004) in the TA, CC, and CS, respectively, compared with animals aged 30 days. After 30 days of age, the concentration gradually and significantly increased until 240 days of age. In 730-day old animals, the concentration, compared with the previous age group, was unchanged in the CC and decreased by 20% (p<0.004) in the TA. CONCLUSIONS:Elastic fiber contents in the rabbit penis correlate with properties of penile tissues. Although after one month of age there is a gradual increase in these concentrations, in two-year old animals this trend is interrupted, which suggests that this could be an early alteration due to senescence.

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“…It is noteworthy that these interruptions in the trend of gradual increase are roughly simultaneous with early and age-related degenerative alterations that affect intervertebral disks 24 , lens 25 , and fertility-associated trace elements 26 of rabbits. But more importantly, the same study that described continuous changes in testicular structure of rabbits until an age of two years, also showed that, at this time point, hypospermatogenesis is already noticeable 28 Experimental evidences from other animals and humans not only support this contention, but also highlight its implications.…”

Section: Discussionmentioning

confidence: 99%

“…It should be noted also that correlations between extracellular matrix composition and age are particularly relevant in short-lived animals such as the rabbit. , lens 25 , and in the serum levels of fertility-associated trace elements 26 . Notably, changes in sexual behavior, as denoted by increased sexual exhaustion and impaired ejaculation 27 , as well as hypospermatogenesis 28 , have been shown to take place at around 20 months of age.…”

Section: Introductionmentioning

confidence: 99%

812 Age-Related Changes in the Concentration of Elastic Fibers in Different Regions of the Rabbit Penis

Cardoso¹,

Costa²,

Chagas³

et al. 2013

Journal of Urology

0

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PURPOSE:To investigate whether elastic fiber content in the corpus cavernosum (CC), corpus spongiosum (CS) and tunica albuginea (TA) of the rabbit penis undergoes modifications with age. METHODS:Rabbits were sacrificed, in groups of ten animals each, at 30, 120, 240, and 730 days of age. Histological sections were obtained from the penile middle shaft and were stained with Weigert's resorsin fuchsin. The content of elastic fibers was determined using stereological methods, and was expressed as volume fraction. RESULTS:At 730 days of age, elastic fiber content was increased by 54% (p<0.004), 78% (p<0.004), and 87% (p<0.004) in the TA, CC, and CS, respectively, compared with animals aged 30 days. After 30 days of age, the concentration gradually and significantly increased until 240 days of age. In 730-day old animals, the concentration, compared with the previous age group, was unchanged in the CC and decreased by 20% (p<0.004) in the TA. CONCLUSIONS:Elastic fiber contents in the rabbit penis correlate with properties of penile tissues. Although after one month of age there is a gradual increase in these concentrations, in two-year old animals this trend is interrupted, which suggests that this could be an early alteration due to senescence.

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Age-related compaction of lens fibers affects the structure and optical properties of rabbit lenses

Abstract: Background: The goal of this investigation was to correlate particular age-related structural changes (compaction) to the amount of scatter in rabbit lenses and to determine if significant fiber compaction occurred in the nuclear and inner cortical regions.

Cited by 12 publications

References 53 publications

The Common Modification in αA-Crystallin in the Lens, N101D, Is Associated with Increased Opacity in a Mouse Model

The Common Modification in αA-Crystallin in the Lens, N101D, Is Associated with Increased Opacity in a Mouse Model

Age-related changes in the concentration of elastic fibers in different regions of the rabbit penis

812 Age-Related Changes in the Concentration of Elastic Fibers in Different Regions of the Rabbit Penis

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