Optical dysfunction of the crystalline lens in aquaporin-0-deficient mice

Shiels, Alan; Bassnett, Steven; Varadaraj, K.; Mathias, Richard T.; Al-Ghoul, K. J.; Kuszak, J.R.; Donoviel, Dorit B.; Lilleberg, Stan L.; Friedrich, Glenn A.; Zambrowicz, Brian

doi:10.1152/physiolgenomics.00078.2001

Cited by 127 publications

(145 citation statements)

References 32 publications

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“…However, three natural AQP0 mutations in human (Berry et al, 2000;Francis et al, 2000a,b;Geyer et al, 2006), and three in mice (Cataract Fraser, Cat Fr : Shields and Griffin, 1993;Shiels et al, 2000; Cataract lens opacity, Cat lop : Shiels and Bassnett, 1996;Cataract Tohoku, Cat Tohm : Okamura et al, 2003) have been associated with autosomal dominant cataracts. Moreover, targeted inactivation of AQP0 in mice resulted in cataract (Shiels et al, 2001). These data on humans and mice illustrate the importance of AQP0 for lens transparency and homeostasis.…”

Section: Introductionmentioning

confidence: 67%

“…Studies on AQP0 knockout mouse lens showed an 80% reduction in the fiber cell membrane water permeability compared to the wild type lens (Shiels et al, 2001). Several research groups have investigated the expression, localization (Patil et al, 1997;Hamann et al, 1998;Zampighi et al, 2003;Varadaraj et al, 2005), and interaction of this protein with other lens proteins (Zampighi et al, 2002;Tan et al, 2004;Yu and Jiang, 2004;Fan et al, 2005;Yu et al, 2005;Rose et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Functional expression of aquaporins in embryonic, postnatal, and adult mouse lenses

Varadaraj

Kumari

Mathias

2007

Developmental Dynamics

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Aquaporin 0 (AQP0) and AQP1 are expressed in the lens, each in a different cell type, and their functional roles are not thoroughly understood. Our previous study showed that these two AQPs function as water transporters. In order to further understand the functional significance of these two different aquaporins in the lens, we investigated their initiation and continued expression. AQP0 transcript and protein were first detected at embryonic stage (E) 11.25 in the differentiating primary fiber cells of the developing lens; its synthesis continued through the adult stage in the secondary fiber cells. Low levels of AQP1 expression were first seen in lens anterior epithelial cells at E17.5; following postnatal day (P) 6.5, the expression gradually progressed towards the equatorial epithelial cells. In the postnatal lens, the increase in membrane water permeability of epithelial cells and lens transparency coincides with the increase in AQP1 expression. AQP1 expression reaches its peak at P30 and continues through the adult stage both in the anterior and equatorial epithelial cells. The enhancement in AQP1 expression concomitant with the increase in the size of the lens suggests the progression in the establishment of the lens microcirculatory system. In vitro and in vivo studies show that both aquaporins share at least one important function, which is water transport in the lens microcirculatory system. However, the temporal expression of these two AQPs suggests an apparently unique role/s in lens development and transparency. To our knowledge, this is the first report on the expression patterns of AQP0 and AQP1 during lens development and differentiation and their relation to lens transparency. Developmental Dynamics 236:1319 -1328, 2007.

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Section: Introductionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Functional expression of aquaporins in embryonic, postnatal, and adult mouse lenses

Varadaraj

Kumari

Mathias

2007

Developmental Dynamics

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“…Mutations in AQP0 are associated with hereditary cataracts in mice and humans Shiels et al, 2001). Cataract-producing AQP0 mutations are thought to produce endoplasmic reticulum-retained and non-functional AQP0 Geyer et al, 2006); however, the mechanism linking AQP0 loss-of-function and cataracts remains unclear.…”

Section: Aqp0 Mutations Cause Congenital Cataractsmentioning

confidence: 99%

“…Cataract-producing AQP0 mutations are thought to produce endoplasmic reticulum-retained and non-functional AQP0 Geyer et al, 2006); however, the mechanism linking AQP0 loss-of-function and cataracts remains unclear. Proposed mechanisms include loss of AQP0-facilitated fiber-fiber adherence (Shiels et al, 2001), and impaired fiber cell dehydration (Fotiadis et al, 2000).…”

Section: Aqp0 Mutations Cause Congenital Cataractsmentioning

confidence: 99%

Functions of aquaporins in the eye

Verkman

Ruiz-Ederra

Levin

2008

Progress in Retinal and Eye Research

172

117

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The aquaporins (AQPs) are integral membrane proteins whose main function is to transport water across cell membranes in response to osmotic gradients. At the ocular surface, AQP1 is expressed in corneal endothelium, AQP3 and AQP5 in corneal epithelium, and AQP3 in conjunctival epithelium. AQPs are also expressed in lens fiber cells (AQP0), lens epithelium (AQP1), ciliary epithelium (AQP1, AQP4) and retinal Müller cells (AQP4). Mutations in AQP0 produce congenital cataracts in humans. Analysis of knockout mice lacking individual AQPs suggests their involvement in maintenance of corneal and lens transparency, corneal epithelial repair, intraocular pressure regulation, retinal signal transduction and retinal swelling following injury. The mouse phenotype findings implicate AQPs as potential drug targets for therapy of elevated intraocular pressure and ocular disorders involving the cornea, lens and retina. However, much research remains in defining cell-level mechanisms for the ocular AQP functions, in establishing the relevance to human eye disease of conclusions from knockout mice, and in developing AQPmodulating drugs.

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“…On protein reconstitution, arrays of junctional octamers, proposed to link two cells together, have also been observed (12). Loss of AQP0 leads to disorganized fiber cells and lens opacity (18,43,44), raising the question of whether this protein serves primarily as a water channel that functions in water homeostasis and microcirculation of nutrients and waste products (45), or as a cell-adhesion molecule (12,(14)(15)(16) that promotes the optically critical close apposition of fiber cells, or both. A related question is the functional significance of the low permeability of AQP0 relative to other aquaporins.…”

Section: Biological Relevance Of Slow Transport By Aqp0 and Implicatimentioning

confidence: 99%

Dynamic control of slow water transport by aquaporin 0: Implications for hydration and junction stability in the eye lens

Jensen

Dror

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Aquaporin 0 (AQP0), the most abundant membrane protein in mammalian lens fiber cells, not only serves as the primary water channel in this tissue but also appears to mediate the formation of thin junctions between fiber cells. AQP0 is remarkably less water permeable than other aquaporins, but the structural basis and biological significance of this low permeability remain uncertain, as does the permeability of the protein in a reported junctional form. To address these issues, we performed molecular dynamics (MD) simulations of water transport through membrane-embedded AQP0 in both its (octameric) junctional and (tetrameric) nonjunctional forms. From our simulations, we measured an osmotic permeability for the nonjunctional form that agrees with experiment and found that the distinct dynamics of the conserved, lumen-protruding side chains of Tyr-23 and Tyr-149 modulate water passage, accounting for the slow permeation. The junctional and nonjunctional forms conducted water equivalently, in contrast to a previous suggestion based on static crystal structures that water conduction is lost on junction formation. Our analysis suggests that the low water permeability of AQP0 may help maintain the mechanical stability of the junction. We hypothesize that the structural features leading to low permeability may have evolved in part to allow AQP0 to form junctions that both conduct water and contribute to the organizational structure of the fiber cell tissue and microcirculation within it, as required to maintain transparency of the lens.membrane ͉ MD simulation ͉ water channel ͉ permeability ͉ cell adhesion

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Optical dysfunction of the crystalline lens in aquaporin-0-deficient mice

Cited by 127 publications

References 32 publications

Functional expression of aquaporins in embryonic, postnatal, and adult mouse lenses

Functional expression of aquaporins in embryonic, postnatal, and adult mouse lenses

Functions of aquaporins in the eye

Dynamic control of slow water transport by aquaporin 0: Implications for hydration and junction stability in the eye lens

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