Seeing is believing! The optical properties of the eye lens are dependent upon a functional intermediate filament cytoskeleton

Perng, Ming Der; Quinlan, Roy A.

doi:10.1016/j.yexcr.2004.11.021

Cited by 31 publications

(37 citation statements)

References 68 publications

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“…The mechanism by which CP49 mutants cause a cataract is not known. The analysis of both CP49-and filensin-null mice support the hypothesis that these IF proteins are required to maintain the transparency of the lens (Perng and Quinlan, 2005;Perng et al, 2007). Mutations in both murine and human γ-crystallins can alter their aggregation properties such that they accumulate in the nucleus of primary lens fibre cells and eventually induce cataracts, possibly by the initial depletion of transcription factors, similar to a mechanism postulated for huntington (Sandilands et al, 2002).…”

Section: Journal Of Cell Science 121 (22)supporting

confidence: 57%

“…We found no evidence for an altered differentiation of lens fibre cells in VimR 113 C mice, making such a mechanism unlikely. The chaperones αA-and αB-crystallin are closely associated with the lens IF cytoskeleton and have been shown to increase the solubility of vimentin in vitro, implying that they may be involved in regulating vimentin reorganisation in vivo (Perng and Quinlan, 2005). In fact, mutations in αB-crystallin cause polar cataracts and a myofibrillar myopathy that is very similar to desmin myopathies, thus supporting an interdependence of IF and αB-crystallin (Graw, 2004;Vicart et al, 1998).…”

Section: Journal Of Cell Science 121 (22)mentioning

confidence: 97%

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A dominant vimentin mutant upregulates Hsp70 and the activity of the ubiquitin-proteasome system, and causes posterior cataracts in transgenic mice

Bornheim

Müller

Reuter

et al. 2008

Journal of Cell Science

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Vimentin is the main intermediate filament (IF) protein of mesenchymal cells and tissues. Unlike other IF–/– mice, vimentin–/– mice provided no evidence of an involvement of vimentin in the development of a specific disease. Therefore, we generated two transgenic mouse lines, one with a (R113C) point mutation in the IF-consensus motif in coil1A and one with the complete deletion of coil 2B of the rod domain. In epidermal keratins and desmin, point mutations in these parts of the α-helical rod domain cause keratinopathies and desminopathies, respectively. Here, we demonstrate that substoichiometric amounts of vimentin carrying the R113C point mutation disrupted the endogenous vimentin network in all tissues examined but caused a disease phenotype only in the eye lens, leading to a posterior cataract that was paralleled by the formation of extensive protein aggregates in lens fibre cells. Unexpectedly, central, postmitotic fibres became depleted of aggregates, indicating that they were actively removed. In line with an increase in misfolded proteins, the amounts of Hsp70 and ubiquitylated vimentin were increased, and proteasome activity was raised. We demonstrate here for the first time that the expression of mutated vimentin induces a protein-stress response that contributes to disease pathology in mice, and hypothesise that vimentin mutations cause cataracts in humans.

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Section: Journal Of Cell Science 121 (22)supporting

confidence: 57%

Section: Journal Of Cell Science 121 (22)mentioning

confidence: 97%

A dominant vimentin mutant upregulates Hsp70 and the activity of the ubiquitin-proteasome system, and causes posterior cataracts in transgenic mice

Bornheim

Müller

Reuter

et al. 2008

Journal of Cell Science

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“…Lens transparency depends on several factors, most notably the organization of cytoplasmic, cytoskeletal and membrane proteins and cell-cell interactions (4,11,13,(20)(21)(22). Cytoskeletal proteins support an important scaffolding function for the organization of cytosolic and membrane-bound proteins in the lens, with actin-based microfilaments, microtubules and intermediate filaments being confirmed to play an essential in lens transparency (15,23,24).…”

Section: Lens Actin Cytoskeletonmentioning

confidence: 99%

The role of the lens actin cytoskeleton in fiber cell elongation and differentiation

Rao

Maddala

2006

Seminars in Cell & Developmental Biology

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The vertebrate ocular lens is a fascinating and unique transparent tissue that grows continuously throughout life. During the process of differentiation into fiber cells, lens epithelial cells undergo dramatic morphological changes, membrane remodeling, polarization, transcriptional activation and elimination of cellular organelles including nuclei, concomitant with migration towards the lens interior. Most of these events are presumed to be influenced in large part, by dynamic reorganization of the cellular actin cytoskeleton and by intercellular and cell: extracellular matrix interactions. In light of recent and unprecedented advancement in our understanding of the mechanistic bases underlying regulation of actin cytoskeletal dynamics and the role of the actin cytoskeleton in cell function, this review attempts to summarize current knowledge regarding the role of the cellular actin cytoskeleton, in lens fiber cell elongation and differentiation, and regulation of actin cytoskeletal organization in the lens.

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“…[32][33][34]. Recently, they have also been used as a model for quantifying the contribution of speci¯c proteins to lens mechanical properties by computing an extrinsic sti®ness parameter derived from lens compression.…”

Section: Introductionmentioning

confidence: 99%

Inverse elastographic method for analyzing the ocular lens compression test

Reilly

Cleaver

2017

J. Innov. Opt. Health Sci.

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The ocular lens sti®ens dramatically with age, resulting in a loss of function. However, the mechanism of sti®ening remains unknown, at least in part due to di±culties in making reliable measurements of the intrinsic mechanical properties of the lens. Recent experiments have employed manual compression testing to evaluate the sti®ness of murine lenses which have genotypes pertinent to human lens diseases. These experiments compare the extrinsic sti®ness of lenses from the genotype of interest to the wild-type lens in an e®ort to reach conclusions regarding the cellular or molecular basis of lens sti®ening. However, these comparisons are confounded by alterations in lens size and geometry which invariably accompany these genetic manipulations. Here, we utilize manual lens compression to characterize the sti®ness of a porcine lens and a murine lens. An inverse elastographic technique was then developed to estimate the intrinsic shear modulus of each lens as well as the elastic modulus of the lens capsule. The results were in good agreement with the previous literature values.

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Seeing is believing! The optical properties of the eye lens are dependent upon a functional intermediate filament cytoskeleton

Cited by 31 publications

References 68 publications

A dominant vimentin mutant upregulates Hsp70 and the activity of the ubiquitin-proteasome system, and causes posterior cataracts in transgenic mice

A dominant vimentin mutant upregulates Hsp70 and the activity of the ubiquitin-proteasome system, and causes posterior cataracts in transgenic mice

The role of the lens actin cytoskeleton in fiber cell elongation and differentiation

Inverse elastographic method for analyzing the ocular lens compression test

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