Regulation of lens volume: Implications for lens transparency

Donaldson, Paul J.; Chee, Kaa-Sandra N.; Lim, Julie C.; Webb, Kevin F.

doi:10.1016/j.exer.2008.05.011

Cited by 43 publications

(40 citation statements)

References 40 publications

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“…From the present study, however, we now know that within this period the lenses do experience loss of transparency and decrease in volume, but that they show a remarkably rapid recovery despite continued exposure to hyperosmotic stress. In the mammalian lens, it has been shown that permanent damage to cortical fiber cell structure occurs when the mechanisms of lens volume regulation are inhibited (15). In this study, the fact that transparency was recovered and the highly organized architecture of the lens was maintained is evidence that the lenses regulated volume by active cellular mechanisms and remained viable despite long-term exposure to osmotic stress.…”

Section: Discussionmentioning

confidence: 49%

N-acetylhistidine, a novel osmolyte in the lens of Atlantic salmon (Salmo salar L.)

Rhodes

Breck²,

Waagbø³

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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-Volume homeostasis is essential for the preservation of lens transparency and this is of particular significance to anadromous fish species where migration from freshwater to seawater presents severe osmotic challenges. In Atlantic salmon (Salmo salar L.), aqueous humor (AH) osmolality is greater in fish acclimated to seawater compared with young freshwater fish, and levels of lens N-acetylhistidine (NAH) are much higher in seawater fish. Here we investigate NAH as an osmolyte in the lenses of salmon receiving diets either with or without histidine supplementation. In the histidine-supplemented diet (HD) histidine content was 14.2 g/kg, and in the control diet (CD) histidine content was 8.9 g/kg. A transient increase in AH osmolality of 20 mmol/kg was observed in fish transferred from freshwater to seawater. In a lens culture model, temporary decreases in volume and transparency were observed when lenses were exposed to hyperosmotic conditions. A positive linear relationship between extracellular osmolality and lens NAH content was also observed, whereas there was no change in lens histidine content. Hypoosmotic exposure stimulated [ 14 C]-histidine efflux by 9.2-and 2.6-fold in CD and HD lenses, respectively. NAH efflux, measured by HPLC, was stimulated by hypoosmotic exposure to a much greater extent in HD lenses. In vivo, lens NAH increased in response to elevated AH osmolality in HD but not CD fish. In conclusion, NAH has an important and novel role as a compatible osmolyte in salmon lens. Furthermore, it is the major osmolyte that balances increases in AH osmolality when fish move from freshwater to seawater. A deficiency in NAH would lead to a dysfunction of the normal osmoregulatory processes in the lens, and we propose that this would contribute to cataract formation in fish deficient in histidine. histidine PREVALENCE OF CATARACT IN farmed Atlantic salmon (Salmo salar L.) has increased in recent years (3) and this has been linked to the removal of a rich source of dietary histidine (blood meal) (7). Several recent studies have investigated the possible causes of cataract in farmed salmon (6, 9, 30), although the mechanisms involved remain to be elucidated.Osmotic stress has been shown to contribute to cataract formation in multiple species, including man (19). Efficient volume regulation is crucial for the maintenance of lens transparency and disruption to the tightly packed and highly ordered cells and proteins that make up the lens will cause a loss of lens transparency. In fish there are numerous examples where osmotic factors have been shown to play a role in cataract development (20), and the anadromous life cycle of the Atlantic salmon exposes the fish to particularly severe osmotic stress. The early part of salmon development is spent in freshwater as parr followed by transformation to smolts before entering the sea. Despite the physiological changes associated with parr-smolt transformation, a preadaption for life in seawater, reversible osmotic cataracts, are commonly described immediately aft...

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Section: Discussionmentioning

confidence: 49%

N-acetylhistidine, a novel osmolyte in the lens of Atlantic salmon (Salmo salar L.)

Rhodes

Breck²,

Waagbø³

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Cataracts, the leading cause of blindness in the world, develop in humans with mutations in AQP0 (Francis et al, 2000; Varadaraj et al, 2008; Verkman, 2003) and in mice deficient in the gene for AQP0 (Shiels et al, 2001; Verkman et al, 2008). To maintain lens transparency, the fiber cell volume and water content must be tightly regulated (Donaldson et al, 2009). Since the lens is avascular to prevent light scattering, volume regulation depends on an internal microcirculation, with AQP0 playing an important role (Donaldson et al, 2001, 2009; Mathias et al, 2007; Shiels et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

The water permeability of lens aquaporin-0 depends on its lipid bilayer environment

Tong

Canty

Briggs

et al. 2013

Experimental Eye Research

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Aquaporin-0 (AQP0), the primary water channel in lens fiber cells, is critical to lens development, organization, and function. In the avascular lens there is thought to be an internal microcirculation associated with fluid movement. Although AQP0 is known to be important in fluid fluxes across membranes, the water permeability of this channel has only been measured in Xenopus oocytes and in outer lens cortical membranes, but not in inner nuclear membranes, which have an increased cholesterol/phospholipid ratio. Here we measure the unit water permeability of AQP0 in different proteoliposomes with cholesterol/phospholipid ratios and external pHs similar to those found in the cortex and nucleus of the lens. Osmotic stress measurements were performed with proteoliposomes containing AQP0 and three different lipids mixtures: (1) phosphatidylcholine (PC) and phosphatidylglycerol (PG), (2) PC, PG, with 40 mol% cholesterol, and (3) sphingomyelin (SM), PG, with 40 mol% cholesterol. At pH 7.5 the unit permeabilities of AQP0 were 3.5 ± 0.5 ± 10−14 cm3/s (mean ± SEM), 1.1 ± 0.1 × 10−14 cm3/s, and 0.50 ± 0.04 × 10−14 cm3/s in PC:PG, PC:PG:cholesterol, and SM:PG:cholesterol, respectively. For lipid mixtures at pH 6.5, corresponding to conditions found in the lens nucleus, the AQP0 permeabilities were 1.5 ± 0.4 × 10−14 cm3/s and 0.76 ± 0.03 × 10−14 cm3/s in PC:PG:cholesterol and SM:PG:cholesterol, respectively. Thus, although AQP0 unit permeability can be modified by changes in pH, it is also sensitive to changes in bilayer lipid composition, and decreases with increasing cholesterol and SM content. These data imply that AQP0 water permeability is regulated by bilayer lipid composition, so that AQP0 permeability would be significantly less in the lens nucleus than in the lens cortex.

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“…43 Abnormalities in ion and water transport mechanisms have previously been suggested to be important in cataract formation. 44,45 We would hypothesize that cataracts are formed in the patients with sdCHC because the mutant (misfolded) glut1 protein is expressed in the lens epithelium where it leaks cations and undermines this convective microcirculatory system.…”

Section: Cataractsmentioning

confidence: 99%

Stomatin-deficient cryohydrocytosis results from mutations in SLC2A1: a novel form of GLUT1 deficiency syndrome

Flatt

Guizouarn²,

Burton

et al. 2011

Blood

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The hereditary stomatocytoses are a series of dominantly inherited hemolytic anemias in which the permeability of the erythrocyte membrane to monovalent cations is pathologically increased. The causative mutations for some forms of hereditary stomatocytosis have been found in the transporter protein genes, RHAG and SLC4A1. Glucose transporter 1 (glut1) deficiency syndromes (glut1DSs) result from mutations in SLC2A1, encoding glut1. Glut1 is the main glucose transporter in the mammalian blood-brain barrier, and glut1DSs are manifested by an array of neurologic symptoms. We have previously reported 2 cases of stomatindeficient cryohydrocytosis (sdCHC), a rare form of stomatocytosis associated with a cold-induced cation leak, hemolytic anemia, and hepatosplenomegaly but also with cataracts, seizures, mental retardation, and movement disorder. We now show that sdCHC is associated with mutations in SLC2A1 that cause both loss of glucose transport and a cation leak, as shown by expression studies in Xenopus oocytes. On the basis of a 3-dimensional model of glut1, we propose potential mechanisms underlying the phenotypes of the 2 mutations found. We investigated the loss of stomatin during erythropoiesis and find this occurs during reticulocyte maturation and involves endocytosis. The molecular basis of the glut1DS, paroxysmal exercise-induced dyskinesia, and sdCHC phenotypes are compared and discussed. (Blood. 2011;118(19): 5267-5277)

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Regulation of lens volume: Implications for lens transparency

Cited by 43 publications

References 40 publications

N-acetylhistidine, a novel osmolyte in the lens of Atlantic salmon (Salmo salar L.)

N-acetylhistidine, a novel osmolyte in the lens of Atlantic salmon (Salmo salar L.)

The water permeability of lens aquaporin-0 depends on its lipid bilayer environment

Stomatin-deficient cryohydrocytosis results from mutations in SLC2A1: a novel form of GLUT1 deficiency syndrome

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